Browse result page of ThPDB2
This is the result page of the browse module of ThPDB2. This page gives the information about the query submitted by the user as per the browse category. Further details of the entries can be seen by clicking on the ID or THPP_ID. Further the user can sort the entries on the basis of various fields by clicking on the respective headers. The user can also download the results in various formats.
Tabular representation:
| ID | THPP_ID | Therapeutic Name | Sequence | Molecular Weight | Chemical Formula | Isoelectric Point | Hydrophobicity | Melting Point | Half Life | Description | Disease/Indication | Pharmacodynamics | Mechanism of Action | Toxicity | Metabolism | Absorption | Volume of Distribution | Clearance | Categories | Patent Number | Date of Issue | Date of Expiry | Drug Interaction | Target | Brand Name | Company | Brand Description | Prescribed for | Chemical Name | Formulation | Physical Appearance | Route of Administation | Recommended Dosage | Contraindication | Side Effects | Useful Links 1 | Useful Links 2 | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 10098 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | US6440392 | 27-Aug-2002 | 2-Feb-2021 | Eskalith (lithium) | Calcitonin receptor | Calcimar | Sanofi Aventis | Sanofi Aventis | To treat Paget's disease of bone | NA | Each mL of sterile solution contains calcitonin salmon 200 IU. Nonmedicinal ingredients include acetic acid, phenol, sodium acetate, sodium chloride, sodium hydroxide and water for injection. | Solution | Subcutaneous or intramuSubcutaneousular Injection | Based on body weight and injected every 12 hours | Allergy | Feeling light-headed, fainting; or muscle stiffness. | Link | NA | NA |
| 10099 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | US5733569 | 31-Mar-1998 | 31-Mar-2015 | Eskalith-CR (lithium) | NA | NA | NA | NA | For treatment of postmenopausal osteoporosis | NA | NA | NA | NA | NA | NA | Swelling in your feet | Link | NA | NA |
| 10100 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | Foscavir (foscarnet) | NA | NA | NA | NA | To reduce high levels of calcium in the blood (hypercalcemia) | NA | NA | NA | NA | NA | NA | Swelling or irritation of the skin where an injection was given. | Link | NA | NA |
| 10101 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | Lithium Carbonate ER (lithium) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Warmth, redness, itching, or tingly feeling under your skin; nausea, loss of appetite, stomach pain | NA | NA | NA |
| 10102 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | Lithobid (lithium) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Vomiting; skin rash or itching; increased urination, especially at night; eye pain | NA | NA | NA |
| 10103 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | Lithonate (lithium) | NA | Fortical | Upsher-Smith Laboratories, Inc., Physicians Total Care, Inc. | Upsher-Smith Laboratories, Inc., Physicians Total Care, Inc. | Used to treat osteoporosis in women who have been in menopause for at least 5 years. To be used along with adequate calcium and vitamin D intake. | NA | Calcitonin-salmon 2200 International Units/mL, corresponding to 200 International Units per actuation (0.09 mL) and Sodium Chloride, Citric Acid, Phenylethyl Alcohol, Benzyl Alcohol, Polysorbate 80, Hydrochloric Acid or Sodium Hydroxide (added as necess | Nasal spray | Intranasal use | Each spray delivers 200 International Units calcitonin-salmon in a volume of 0.09 mL. | Allergy | Tremors or shaking, feeling like you might pass out, severe nasal irritation. | Link | NA | NA |
| 10104 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | Lithotabs (lithium) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Bleeding from your nose, runny or stuffy nose, dryness, itching, tenderness, or general discomfort of your nose, crusting, scabs, or sores inside your nose, redness in or around your nose. | Link | NA | NA |
| 10105 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Warmth, redness, or tingly feeling under your skin, headache, back pain, nausea. | Link | NA | NA |
| 10106 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | NA | NA | Miacalcin | Novartis, Mylan Institutional LLC, Physicians Total Care, Inc., Sebela Pharmaceuticals Inc. | Novartis, Mylan Institutional LLC, Physicians Total Care, Inc., Sebela Pharmaceuticals Inc. | Miacalcin Nasal Spray is used to treat osteoporosis in women who have been in menopause for at least 5 years. To be supplemented with adequate calcium and vitamin D intake. | NA | Each milliliter contains calcitonin-salmon 200 I.U., acetic acid, USP, 2.25 mg; phenol, USP, 5.0 mg; sodium acetate trihydrate, USP, 2.0 mg; sodium chloride, USP, 7.5 mg; water for injection, USP, qs to 1.0 mL | Solution | Subcutaneous or intramuSubcutaneousular Injection | For treatment of symptomatic Paget's disease of bone, 100 International Units (0.5 mL) per day administered subcutaneously or intramuscularly and for early treatment of hypercalcemia, 4 International Units/kg body weight every 12 hours by subcutaneous or | Allergic, nasal or sinus problem such as nasal deformities, a chronic infection, or nasal pain. | Tremors or shaking, feeling like you might pass out, severe nasal irritation. | Link | NA | NA |
| 10107 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Bleeding from your nose, runny or stuffy nose, dryness, itching, tenderness, or general discomfort of your nose. | Link | NA | NA |
| 10108 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Crusting, scabs, or sores inside your nose, redness in or around your nose. | Link | NA | NA |
| 10109 | Th1014 | Salmon Calcitonin | >Th1014_Salmon_Calcitonin CSNLSTCVLGKLSQELHKLQTYPRTNTGSGTP | 3431.853 | C145H240N44O48S2 | 8.86 | -0.537 | NA | 0.83-1.33 hours | Synthetic peptide of 32 residues, formulated as a nasal spray. | Used for the treatment of post-menopausal osteoporosis. | Calcitonin inhibits bone removal by osteoclasts and promotes bone formation by osteoblasts, leading to a net increase in bone mass. Calcitonin also reduces plasma calcium levels and enhances secretion of ions in the kidney. | Calcitonin binds to the calcitonin receptor, found mainly in osteoclasts which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. | It is devoid of embryotoxic, teratogenic and mutagenic potential. | Primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. | Rapidly absorbed and eliminated. Bioavailability is high following subcutaneous and intramuscular injection in humans and similar for the two routes of administration (71% and 66%, respectively). | 0.15 to 0.3 L/kg | Studies with injectable calcitonin show increase in the excretion of filtered calcium, phosphate, and sodium by decreasing their tubular reabsorption in the kidney. | Amino Acids, Peptides, and Proteins, Bone Density Conservation Agents, Bone Density, drug effects, Calcitonin Preparations, Calcium Homeostasis, Calcium-Regulating Hormones and Agents, Drugs that are Mainly Renally Excreted, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Nerve Tissue Proteins, Neuropeptides, Parathyroid and Antiparathyroid Agents, Parathyroid Hormones and Analogues, Peptide Hormones, Peptides, Proteins, Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins, Thyroid Products | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Warmth, redness, or tingly feeling under your skin, headache, back pain, nausea. | Link | NA | NA |
| 10584 | Th1120 | Teriparatide | >Th1120_Teriparatide SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF | 4117.715 | C181H291N55O51S2 | NA | NA | NA | NA | Recombinant, human parathyroid hormone (PTH). It is a potent anabolic agent used to treat osteoporosis. It is manufactured and marketed by Eli Lilly and Company. | For the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. Also used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. | Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density. | Teriparatide is the portion of human parathyroid hormone (PTH),amino acid sequence 1 through 34 of the complete molecule which contains amino acid sequence 1 to 84. Endogenous PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. Daily injections of teriparatide stimulate new bone formation leading to increased bone mineral density. | Effects of overexposure may include headaches, dizziness, dizziness, decreased blood pressured, decreased fetal survival, leg cramps, changes in clinical chemistry including increased in blood levels of calcium, decreased serum phosphorous, and increased urinary calcium and phosphorus. | Hepatic | Bioavailability is 95% following subcutaneous injection. | 0.12 L/kg | * 62 L/hr [Women] * 94 L/hr [Men] | Bone Density Conservation Agents | US6977077 | 20-12-2005 | 19-08-2019 | NA | Parathyroid hormone/parathyroid hormone-related peptide receptor | Forteo | Eli Lilly and Company | Eli Lilly and Company | Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture, Increase of Bone Mass in Men with Primary or Hypogonadal Osteoporosis at High Risk for Fracture, Treatment of Men and Women with Glucocorticoid-Induced Osteoporosis at High Risk for Fracture. | NA | Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. Each cartridge, pre-assembled into a delivery device, delivers 20 mcg of teriparatide per dose each day for up to 28 days. | Sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection | Subcutaneous | Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture. The recommended dose is 20 mcg subcutaneously once a day. Increase of Bone Mass in Men with Primary or Hypogonadal Osteoporosis at High Risk for Fracture. he recommended dose is 20 mcg subcutaneously once a day. | Hypersensitivity to teriparatide or to any of its excipients. Reactions have included angioedema and anaphylaxis | NA | Link | NA | NA |
| 10585 | Th1120 | Teriparatide | >Th1120_Teriparatide SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF | 4117.715 | C181H291N55O51S2 | NA | NA | NA | NA | Recombinant, human parathyroid hormone (PTH). It is a potent anabolic agent used to treat osteoporosis. It is manufactured and marketed by Eli Lilly and Company. | For the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. Also used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. | Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density. | Teriparatide is the portion of human parathyroid hormone (PTH),amino acid sequence 1 through 34 of the complete molecule which contains amino acid sequence 1 to 84. Endogenous PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. Daily injections of teriparatide stimulate new bone formation leading to increased bone mineral density. | Effects of overexposure may include headaches, dizziness, dizziness, decreased blood pressured, decreased fetal survival, leg cramps, changes in clinical chemistry including increased in blood levels of calcium, decreased serum phosphorous, and increased urinary calcium and phosphorus. | Hepatic | Bioavailability is 95% following subcutaneous injection. | 0.12 L/kg | * 62 L/hr [Women] * 94 L/hr [Men] | Bone Density Conservation Agents | US6770623 | 8-Mar-2004 | 12-Aug-2018 | NA | Parathyroid hormone/parathyroid hormone-related peptide receptor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10586 | Th1120 | Teriparatide | >Th1120_Teriparatide SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF | 4117.715 | C181H291N55O51S2 | NA | NA | NA | NA | Recombinant, human parathyroid hormone (PTH). It is a potent anabolic agent used to treat osteoporosis. It is manufactured and marketed by Eli Lilly and Company. | For the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. Also used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. | Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density. | Teriparatide is the portion of human parathyroid hormone (PTH),amino acid sequence 1 through 34 of the complete molecule which contains amino acid sequence 1 to 84. Endogenous PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. Daily injections of teriparatide stimulate new bone formation leading to increased bone mineral density. | Effects of overexposure may include headaches, dizziness, dizziness, decreased blood pressured, decreased fetal survival, leg cramps, changes in clinical chemistry including increased in blood levels of calcium, decreased serum phosphorous, and increased urinary calcium and phosphorus. | Hepatic | Bioavailability is 95% following subcutaneous injection. | 0.12 L/kg | * 62 L/hr [Women] * 94 L/hr [Men] | Bone Density Conservation Agents | CA2314313 | 2-Aug-2005 | 12-Aug-2018 | NA | Parathyroid hormone/parathyroid hormone-related peptide receptor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10587 | Th1120 | Teriparatide | >Th1120_Teriparatide SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF | 4117.715 | C181H291N55O51S2 | NA | NA | NA | NA | Recombinant, human parathyroid hormone (PTH). It is a potent anabolic agent used to treat osteoporosis. It is manufactured and marketed by Eli Lilly and Company. | For the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. Also used to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. | Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density. | Teriparatide is the portion of human parathyroid hormone (PTH),amino acid sequence 1 through 34 of the complete molecule which contains amino acid sequence 1 to 84. Endogenous PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. Daily injections of teriparatide stimulate new bone formation leading to increased bone mineral density. | Effects of overexposure may include headaches, dizziness, dizziness, decreased blood pressured, decreased fetal survival, leg cramps, changes in clinical chemistry including increased in blood levels of calcium, decreased serum phosphorous, and increased urinary calcium and phosphorus. | Hepatic | Bioavailability is 95% following subcutaneous injection. | 0.12 L/kg | * 62 L/hr [Women] * 94 L/hr [Men] | Bone Density Conservation Agents | CA2325371 | 17-08-2004 | 19-08-2019 | NA | Parathyroid hormone/parathyroid hormone-related peptide receptor | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10598 | Th1123 | Denosumab | >Th1123_Denosumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144700 | C6404H9912N1724O2004S50 | NA | NA | NA | 25.4 days | Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010. | Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. | In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. | Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. | In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (= 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials | NA | When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies. | NA | NA | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Blood Proteins,Bone Density Conservation Agents,Cancer immunotherapy,Drugs Affecting Bone Structure and Mineralization,Drugs for Treatment of Bone Diseases,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Musculo-Skeletal System,Proteins,RANK Ligand Blocking Activity,RANK Ligand Inhibitor,Serum Globulins | CA2257247 | 9-Nov-2012 | 15-04-2018 | NA | Tumor necrosis factor ligand superfamily member 11 | Xgeva | Amgen. | Amgen. | Bone Metastasis From Solid Tumors, Giant Cell Tumor Of Bone, Hypercalcemia Of Malignancy | NA | Each single-use vial of Xgeva contains 120 mg denosumab, acetate (18 mM), sorbitol (4.6%), Water for Injection (USP), and sodium hydroxide to a pH of 5.2 | Sterile, preservative-free, clear, colorless to pale yellow solution | NA | Bone Metastasis From Solid Tumors: The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.; Giant Cell Tumor Of Bone: The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.; Hypercalcemia Of Malignancy: The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. | Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma. | Hypocalcemia, Osteonecrosis of the Jaw. | Link | NA | NA |
| 10599 | Th1123 | Denosumab | >Th1123_Denosumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144700 | C6404H9912N1724O2004S50 | NA | NA | NA | 25.4 days | Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010. | Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. | In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. | Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. | In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (= 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials | NA | When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies. | NA | NA | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Blood Proteins,Bone Density Conservation Agents,Cancer immunotherapy,Drugs Affecting Bone Structure and Mineralization,Drugs for Treatment of Bone Diseases,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Musculo-Skeletal System,Proteins,RANK Ligand Blocking Activity,RANK Ligand Inhibitor,Serum Globulins | CA2274987 | 24-01-2012 | 22-12-2017 | NA | Tumor necrosis factor ligand superfamily member 11 | Prolia | Amgen. | Amgen. | Treatment Of Postmenopausal Women With Osteoporosis At High Risk For Fracture,Treatment To Increase Bone Mass In Men With Osteoporosis, Treatment Of Bone Loss In Men Receiving Androgen Deprivation Therapy For Prostate Cancer, Treatment Of Bone Loss In Women Receiving Adjuvant Aromatase Inhibitor Therapy For Breast Cancer | NA | Each 1 mL single-use prefilled syringe of Prolia contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, 0.01% polysorbate 20, Water for Injection (USP), and sodium hydroxide to a pH of 5.2. Each 1 mL single-use vial of Prolia contains 60 mg denosumab (60 mg/mL solution), 4.7% sorbitol, 17 mM acetate, Water for Injection (USP), and sodium hydroxide to a pH of 5.2 | Sterile, preservative-free, clear, colorless to pale yellow solution | NA | NA | Hypocalcemia. Pregnancy. Hypersensitivity | Hypocalcemia, Serious Infections, Dermatologic Adverse Reactions, Osteonecrosis of the Jaw, Atypical Subtrochanteric and Diaphyseal Femoral Fractures | Link | NA | NA |
| 10600 | Th1123 | Denosumab | >Th1123_Denosumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144700 | C6404H9912N1724O2004S50 | NA | NA | NA | 25.4 days | Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010. | Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. | In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. | Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. | In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (= 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials | NA | When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies. | NA | NA | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Blood Proteins,Bone Density Conservation Agents,Cancer immunotherapy,Drugs Affecting Bone Structure and Mineralization,Drugs for Treatment of Bone Diseases,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Musculo-Skeletal System,Proteins,RANK Ligand Blocking Activity,RANK Ligand Inhibitor,Serum Globulins | CA2285746 | 28-09-2010 | 15-04-2018 | NA | Tumor necrosis factor ligand superfamily member 11 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10601 | Th1123 | Denosumab | >Th1123_Denosumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144700 | C6404H9912N1724O2004S50 | NA | NA | NA | 25.4 days | Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010. | Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. | In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. | Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. | In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (= 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials | NA | When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies. | NA | NA | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Blood Proteins,Bone Density Conservation Agents,Cancer immunotherapy,Drugs Affecting Bone Structure and Mineralization,Drugs for Treatment of Bone Diseases,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Musculo-Skeletal System,Proteins,RANK Ligand Blocking Activity,RANK Ligand Inhibitor,Serum Globulins | CA2400929 | 31-05-2011 | 23-02-2021 | NA | Tumor necrosis factor ligand superfamily member 11 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10602 | Th1123 | Denosumab | >Th1123_Denosumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144700 | C6404H9912N1724O2004S50 | NA | NA | NA | 25.4 days | Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010. | Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. | In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. | Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. | In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (= 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials | NA | When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies. | NA | NA | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Blood Proteins,Bone Density Conservation Agents,Cancer immunotherapy,Drugs Affecting Bone Structure and Mineralization,Drugs for Treatment of Bone Diseases,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Musculo-Skeletal System,Proteins,RANK Ligand Blocking Activity,RANK Ligand Inhibitor,Serum Globulins | CA2328140 | 13-03-2012 | 13-05-2019 | NA | Tumor necrosis factor ligand superfamily member 11 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 10603 | Th1123 | Denosumab | >Th1123_Denosumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGITGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDPGTTVIMSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144700 | C6404H9912N1724O2004S50 | NA | NA | NA | 25.4 days | Novel, fully human IgG2 monoclonal antibody, specific to receptor activator of nuclear factor kappa-B ligand (RANKL). It suppresses bone resorption markers in patients suffering from metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Each light chain consists of 215 amino acids and the heavy chain consists of 448 amino acids. FDA approved on June 1, 2010. | Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. | In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. | Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. | In patients with postmenopausal osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the most common adverse reactions (= 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials | NA | When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies. | NA | NA | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Blood Proteins,Bone Density Conservation Agents,Cancer immunotherapy,Drugs Affecting Bone Structure and Mineralization,Drugs for Treatment of Bone Diseases,Globulins,Immunoglobulins,Immunoproteins,Immunosuppressive Agents,Immunotherapy,Musculo-Skeletal System,Proteins,RANK Ligand Blocking Activity,RANK Ligand Inhibitor,Serum Globulins | NA | NA | NA | NA | Tumor necrosis factor ligand superfamily member 11 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| 11984 | Th1275 | Abaloparatide | >Th1275_Abaloparatide AVSEHQLLHDKGKSIQDLRRRELLEKLLXKLHTA | 3961 | C174H300N56O49 | NA | NA | NA | The mean (SD) half-life if 1.7 (0.7) hrs. | Abaloparatide is an analog of PTHrP (parathyroid hormone-related protein). It was approved in April 28, 2017 by the FDA (as Tymlos) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Abaloparatide is a synthetic peptide that is related to hPTHrP and has demonstrated in preclinical testing the potential to widen the anabolic window for bone therapeutics, stimulating bone formation with a limited effect on bone resorption and mineral mobilization. This could enable improved convenience over currently available anabolic therapies, resulting in greater compliance and, ultimately, greater benefit to patients. | Investigated for use/treatment in postmenopausal osteoporosis to reduce vertebral and/or non-vertebral fractures. | Abaloparatide (BA058), a proprietary analog of human parathyroid hormone-related protein (hPTHrP), is currently undergoing clinical trials by the company for the treatment of osteoporosis in postmenopausal women. PTHrP is a critical peptide for promoting new bone formation, with a distinct role from parathyroid hormone, or PTH, which primarily regulates calcium homeostasis and bone resorption. Clinical studies show increased bone mineral density (BMD) and levels of bone formation markers in a dose-response relationship. | In target cells, abaloparatide acts as an agonist on PTH type 1 receptor (PTH1R) and activates both G protein–mediated cAMP signaling and ß-arrestin-mediated ERK-1/2 signaling pathways with similar potency. Abaloparatide binds to RG conformation of PTH1R with greater selectivity that results in more transient cell signalling responses. | Abaloparatide has shown to induce higher incidences of osteosarcoma in a dose-dependent manner in a 2 year carcinogenicity study with female and male rats. This correlation is not known to be reflected in humans, however patients with increased risk of osteosarcoma including Paget's disease, open epiphyses, and skeletal malignancies should avoid this treatment. Abaloparatide may also cause hypercalcemia so should be avoided in patients with pre-existing conditions of primary hyperthyroidism or hypercalcemia. Overdose is commonly associated with hypercalcemia, nausea, vomiting, dizziness, tachycardia, orthostatic hypotension and headache. There is no known antidote for abaloparatide. | Abaloparatide is metabolized into smaller peptide fragments via non-specific proteolytic degradation. | The time it takes to reach peak concentration following subcutaneous administration of 80 mcg abaloparatide ranges from 0.25 to 0.52 hr, with the median time of 0.51hr. The bioavailability in healthy women is 36% following administration. | Vd is approximately 50L. | NA | Bone Density Conservation Agents | NA | NA | NA | NA | Parathyroid hormone/parathyroid hormone-related peptide receptor | NA | NA | NA | NA | NA | NA | NA | NA | NA | 4-[[2-[[2-[[2-[[2-[[2-[[5-amino-2-[[2-[[2-[[6-amino-2-[[2-[[6-amino-2-[[2-[[2-[[2-[[2-[[5-amino-2-[[2-[[2-[[2-[[2-(2-aminopropanoylamino)-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-carboxypropanoyl]amino]hexanoyl]amino]acetyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[1-[[1-[[1-[[6-amino-1-[[1-[[1-[[1-[[6-amino-1-[[1-[[1-[[1-[(1-amino-1-oxopropan-2-yl)amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid | NA | Link | NA | NA |
| 13451 | Th1405 | Eptotermin alfa | >Th1405_Eptotermin_alfa STGSKQRSQNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFRDLGWQDWIIAPEGYAAYYCEGECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISVLYFDDSSNVILKKYRNMVVRACGCH | NA | NA | NA | NA | NA | NA | A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis. Eptotermin alfa is an ingredient in the EMA-withdrawn product Osigraft. | NA | NA | NA | NA | NA | NA | NA | NA | Bone Morphogenetic Proteins | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13452 | Th1405 | Eptotermin alfa | >Th1405_Eptotermin_alfa STGSKQRSQNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFRDLGWQDWIIAPEGYAAYYCEGECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISVLYFDDSSNVILKKYRNMVVRACGCH | NA | NA | NA | NA | NA | NA | A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis. Eptotermin alfa is an ingredient in the EMA-withdrawn product Osigraft. | NA | NA | NA | NA | NA | NA | NA | NA | Drugs Affecting Bone Structure and Mineralization | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13453 | Th1405 | Eptotermin alfa | >Th1405_Eptotermin_alfa STGSKQRSQNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFRDLGWQDWIIAPEGYAAYYCEGECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISVLYFDDSSNVILKKYRNMVVRACGCH | NA | NA | NA | NA | NA | NA | A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis. Eptotermin alfa is an ingredient in the EMA-withdrawn product Osigraft. | NA | NA | NA | NA | NA | NA | NA | NA | Drugs for Treatment of Bone Diseases | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13461 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Bone Morphogenetic Proteins | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13462 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Drugs Affecting Bone Structure and Mineralization | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13463 | Th1406 | Dibotermin alfa | NA | NA | NA | NA | NA | NA | When injected intravenously, the terminal half-life of dibotermin alfa was 16 minutes in rats and 6.7 minutes in cynomolgus monkeys [L1391]. | Dibotermin alfa is a recombinant human bone morphogenetic protein-2 (rhBMP-2) derived from a recombinant Chinese Hamster Ovary (CHO) cell line [FDA Label]. It is implanted in patients undergoing bone surgeries or those with fractures. BMPs are subfamily of the transforming growth factor-ß (TGF-ß) superfamily that have different actions on the bone matrix [A31946]. BMP-2 is a potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into osteoblasts, thus promoting bone and cartilage formation [A31952]. Through enhancing osteogenesis at the site of implantation, dibotermin alfa accelerates the healing of open tibial shaft fractures and reduces the need for secondary intervention [A31945]. In a prospective clinical study of patients with an open tibial fracture, administration of dibotermin alfa resulted in faster fracture- or wound-healing, significantly fewer secondary invasive interventions, and reduced infection rate post-operation [A31945]. Dibotermin alfa was approved by the EMA in 2002 as Inductos for implantation matrix. In 2004, it was approved by the FDA and is marketed as Infuse. In Infuse, rhBMP is a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated with high-mannose-type glycans [FDA Label]. | - indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation [FDA Label]. - indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition [L1391]. | Dibotermin alfa promotes bone and cartilage formation through anabolic effects in human osteoblastic cells [A31952]. Radiographic, biomechanical and histologic evaluation of the induced bone at the site of implantation supports that induced bone from dibotermin alfa therapy is capable of biological and biochemical function as native bone and repair abilities [L1391]. | In the same pathway shared by endogenous BMPs, recombinant human BMP-2 (rhBMP-2) binds and initiates intracellular signal cascade through an oligomeric transmembrane receptor complex formed by type I and II serine/threonine kinase receptor proteins [A31962]. These BMP receptors are expressed on the surface of mesenchymal cells and upon binding of BMP-2 to the BMP receptor type II, type II receptor phosphorylates and activates type I receptor. Type I receptor may also undergo autophosphorylation. Activated BMP type I receptor then phosphorylates intracellular effector proteins, the receptor-regulated Smads (R-Smads) [A31946]. Smad1, Smad 5 and Smad 8 associate with the Co-Smad, Smad4 and once activated via complex formation, they translocate to the nucleus where they associate with other transcription factors and bind promoters of target genes to control their expression [A31946]. This ultimately results in bone formation at the site of implantation. Dibotermin alfa causes mesenchymal cells to differentiate into cartilage- and bone-forming cells. Implantation of dibotermin alfa in trabecular bone results in transient resorption of the bone surrounding the implant, followed by replacement of degraded matrix by newly differentiated cells [L1391]. In human bone cells isolated from adult mandibulae, recombinant human BMP-2 (rhBMP-2) was shown to stimulate the activity of early biomarkers of osteoblast differentiation, including alkaline phosphatase and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation [A31952]. At concentrations of 500 ng/mL, rhBMP-2 also enhanced the mRNA expression level of PTH/PTH related-peptide receptor in human bone cells [A31952]. There was evidence that rhBMP-2 inhibits 1,25-dihydroxyvitamin D3-induced osteocalcin synthesis at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and MMP-1 mRNA expression at concentrations exceeding 500 ng/mL [A31952]. | Supportive treatment is recommended in case of overdose. Use of Inductos in patients undergoing cervical spine surgery in amounts lower than or similar to those for lumbar interbody fusion has been associated with reports of localised oedema severe enough to result in airway compromise [L1391]. There is no evidence of significant hazards on humans based on non-clinical data of acute and repeated exposure toxicity and genotoxicity studies [L1391]. In reproductive toxicity studies in rats, intravenous administration of dibotermin alfa was associated with increased fetal weight and increased fetal ossification. The clinical relevance of this effect is unknown [L1391]. In human tumour cell lines in vitro, dibotermin alfa did not display any potential for promotion of tumour growth or metastasis [L1391]. Studies investigating the carcinogenicity of dibotermin alfa have not been conducted. | NA | Dibotermin alfa is active at the site of implantation with no detection in the serum. In rat studies with radiolabelled dibotermin alfa, the mean residence time at the site of implantation was 4-8 days [L1391]. Peak levels of circulating dibotermin alfa (0.1% of the implanted dose) were observed within 6 hours following implantation [L1391]. | NA | At the site of implantation, dibotermin alfa is expected to be slowly released from the matrix and rapidly cleared when taken up into the systemic circulation [L1391]. | Drugs for Treatment of Bone Diseases | NA | NA | NA | NA | Bone morphogenetic protein receptor type-2,Bone morphogenetic protein receptor type-1A | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13786 | Th1434 | Romosozumab | NA | 145805 | NA | NA | NA | NA | 12.8 days[L9554]. | Romosozumab is a humanized monoclonal antibody indicated for the treatment of osteoperosis in postmenopausal women at high risk of fracture and patients who have failed in other treatments or are intolerant to other osteoperosis therapies[L9554]. Romosozumab prevents bone resorption and induces the formation of bone though it is associated with an increased risk of cardiac death, heart attack, and stroke in one study[L5921,L5924]. In a comparison study of post menopausal women with osteoporosis and a past fracture, romosozumab for 12 months followed by alendronic acid for 12 months was superior to alendronic acid alone for 24 months[A177071]. Romosozumab also demonstrates a faster and larger increase in bone density than teriparatide[A177050]. Romosozumab is marketed in the United States by Amgen under the brand name Evinity[L5921]. Romosozumab was granted FDA approval on April 9,2019[L5921]. | Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments[L9554]. | Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin[L9554]. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts[A177056,A177062]. | Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway[A177056]. Romosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6[A177056,A177062]. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts[A177062]. Sclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL)[A177062]. Romosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption[A177056,A177062]. Both effects from the same therapy have not been seen in other osteoporosis treatments to date[A177056]. | There are no significant differences in pharmacokinetics cross age, sex, race, progression of osteoporosis, past history of alendronic acid prescribing, and all stages of renal impairment[L9554]. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemia[L9554]. A patient's weight will affect their level of romosozumab exposure[L9554]. Romosozumab has not been shown to be associated with carcinogenicity or impairment of fertility, and is not expected to be mutagenic[L9554]. Romosozumab is not indicated in pregnancy, lactation, or pedatric patients[L9554]. Romosozumab is associated with skeletal defects in the offspring of rats given romosozumab and is detected in the excreted milk[L9554]. Romosozumab is currently undergoing post marketing surveillance to ensure the risk of major adverse cardiac events is not being underestimated[L5924]. There is currently an expected hazard ratio of 1.30 compared to current treatments for osteoporosis, though hip and vertebral fractures may have an equal impact on overall quality of life[L5924]. | The metabolism of romosozumab has not been clarified, however it is expected to be degraded into small peptides and amino acids like other protein drugs[L9554]. | Romosozumab reaches peak concentration within 2 to 7 days with a median time of 5 days[L9554]. Subcutaneous bioavailability is 50 to 70%[A177056,A177062]. | 3.92L[L9554]. | 0.38mL/hr/kg[L9554]. | Bone Anabolic Agents | NA | NA | NA | NA | Sclerostin | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13787 | Th1434 | Romosozumab | NA | 145805 | NA | NA | NA | NA | 12.8 days[L9554]. | Romosozumab is a humanized monoclonal antibody indicated for the treatment of osteoperosis in postmenopausal women at high risk of fracture and patients who have failed in other treatments or are intolerant to other osteoperosis therapies[L9554]. Romosozumab prevents bone resorption and induces the formation of bone though it is associated with an increased risk of cardiac death, heart attack, and stroke in one study[L5921,L5924]. In a comparison study of post menopausal women with osteoporosis and a past fracture, romosozumab for 12 months followed by alendronic acid for 12 months was superior to alendronic acid alone for 24 months[A177071]. Romosozumab also demonstrates a faster and larger increase in bone density than teriparatide[A177050]. Romosozumab is marketed in the United States by Amgen under the brand name Evinity[L5921]. Romosozumab was granted FDA approval on April 9,2019[L5921]. | Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments[L9554]. | Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin[L9554]. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts[A177056,A177062]. | Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway[A177056]. Romosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6[A177056,A177062]. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts[A177062]. Sclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL)[A177062]. Romosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption[A177056,A177062]. Both effects from the same therapy have not been seen in other osteoporosis treatments to date[A177056]. | There are no significant differences in pharmacokinetics cross age, sex, race, progression of osteoporosis, past history of alendronic acid prescribing, and all stages of renal impairment[L9554]. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemia[L9554]. A patient's weight will affect their level of romosozumab exposure[L9554]. Romosozumab has not been shown to be associated with carcinogenicity or impairment of fertility, and is not expected to be mutagenic[L9554]. Romosozumab is not indicated in pregnancy, lactation, or pedatric patients[L9554]. Romosozumab is associated with skeletal defects in the offspring of rats given romosozumab and is detected in the excreted milk[L9554]. Romosozumab is currently undergoing post marketing surveillance to ensure the risk of major adverse cardiac events is not being underestimated[L5924]. There is currently an expected hazard ratio of 1.30 compared to current treatments for osteoporosis, though hip and vertebral fractures may have an equal impact on overall quality of life[L5924]. | The metabolism of romosozumab has not been clarified, however it is expected to be degraded into small peptides and amino acids like other protein drugs[L9554]. | Romosozumab reaches peak concentration within 2 to 7 days with a median time of 5 days[L9554]. Subcutaneous bioavailability is 50 to 70%[A177056,A177062]. | 3.92L[L9554]. | 0.38mL/hr/kg[L9554]. | Drugs Affecting Bone Structure and Mineralization | NA | NA | NA | NA | Sclerostin | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 13788 | Th1434 | Romosozumab | NA | 145805 | NA | NA | NA | NA | 12.8 days[L9554]. | Romosozumab is a humanized monoclonal antibody indicated for the treatment of osteoperosis in postmenopausal women at high risk of fracture and patients who have failed in other treatments or are intolerant to other osteoperosis therapies[L9554]. Romosozumab prevents bone resorption and induces the formation of bone though it is associated with an increased risk of cardiac death, heart attack, and stroke in one study[L5921,L5924]. In a comparison study of post menopausal women with osteoporosis and a past fracture, romosozumab for 12 months followed by alendronic acid for 12 months was superior to alendronic acid alone for 24 months[A177071]. Romosozumab also demonstrates a faster and larger increase in bone density than teriparatide[A177050]. Romosozumab is marketed in the United States by Amgen under the brand name Evinity[L5921]. Romosozumab was granted FDA approval on April 9,2019[L5921]. | Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments[L9554]. | Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin[L9554]. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts[A177056,A177062]. | Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway[A177056]. Romosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6[A177056,A177062]. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts[A177062]. Sclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL)[A177062]. Romosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption[A177056,A177062]. Both effects from the same therapy have not been seen in other osteoporosis treatments to date[A177056]. | There are no significant differences in pharmacokinetics cross age, sex, race, progression of osteoporosis, past history of alendronic acid prescribing, and all stages of renal impairment[L9554]. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemia[L9554]. A patient's weight will affect their level of romosozumab exposure[L9554]. Romosozumab has not been shown to be associated with carcinogenicity or impairment of fertility, and is not expected to be mutagenic[L9554]. Romosozumab is not indicated in pregnancy, lactation, or pedatric patients[L9554]. Romosozumab is associated with skeletal defects in the offspring of rats given romosozumab and is detected in the excreted milk[L9554]. Romosozumab is currently undergoing post marketing surveillance to ensure the risk of major adverse cardiac events is not being underestimated[L5924]. There is currently an expected hazard ratio of 1.30 compared to current treatments for osteoporosis, though hip and vertebral fractures may have an equal impact on overall quality of life[L5924]. | The metabolism of romosozumab has not been clarified, however it is expected to be degraded into small peptides and amino acids like other protein drugs[L9554]. | Romosozumab reaches peak concentration within 2 to 7 days with a median time of 5 days[L9554]. Subcutaneous bioavailability is 50 to 70%[A177056,A177062]. | 3.92L[L9554]. | 0.38mL/hr/kg[L9554]. | Drugs for Treatment of Bone Diseases | NA | NA | NA | NA | Sclerostin | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15403 | Th1594 | Burosumab | >Th1594_Burosumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISGSTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144100 | C6388H9904N1700O2006S46 | NA | NA | NA | About 19 days [L2347]. | Burosumab (KRN23) is an entirely human monoclonal IgG1 antibody that binds excess fibroblast growth factor 23 (FGF23) and has been successfully tested in clinical trials in children with X-linked hypophosphatemic rickets [A32593]. The U.S. Food and Drug Administration approved Crysvita (burosumab) in April 2018. This is the first drug approved to treat adults and children ages 1 year and older with X-linked hypophosphatemia (XLH), which is a rare, inherited form of rickets. X-linked hypophosphatemia causes low circulating levels of phosphorus in the blood. It causes impaired bone growth and development in children and adolescents and issues with bone mineralization throughout a patient’s life [L2346]. XLH is a serious disease which affects about 3,000 children and 12,000 adults in the United States. Most children with XLH suffer from bowed or bent legs, short stature, bone pain and severe dental pain. Some adults with this condition suffer from persistent, unrelenting discomfort and complications, such as joint pain, impaired mobility, tooth abscesses and hearing loss [L2346]. | This drug is indicated for the treatment of X-linked hypophosphatemia with radiological evidence of bone disease in children of 1 year of age and older and adolescents with growing skeletons [L2347]. | This drug has the ability to reduce the loss of phosphate, to improve pathologically low serum phosphate concentrations and other metabolic changes, as well as to reduce the severity of rickets as seen radiographically [L2348]. In summary, this drug works to support of bone mineralization [L2347]. | Burosumab is a recombinant human monoclonal antibody (IgG1) that both binds to and inhibits the actions of fibroblast growth factor 23 (FGF23). By inhibiting this growth factor, burosumab increases the tubular reabsorption of phosphate from the kidney and thus increases serum concentration of 1, 25 dihydroxy-Vitamin D [L2347]. This form of vitamin D enhances intestinal absorption of phosphate and calcium, supporting bone mineralization [L2351]. | The toxicity of Crysvita can be classified into several categories [L2347]: **Ectopic mineralisation**: Clinically manifested by nephrocalcinosis, has been seen in patients with XLH treated with oral phosphorous and vitamin D analogues. These drugs should be stopped at least 1 week before starting burosumab treatment [L2347]. Monitoring for signs and symptoms of nephrocalcinosis, e.g. by renal ultrasonography, is recommended at the beginning of treatment and at intervals of every 6 months for the first 12 months of treatment, and yearly thereafter. Regular monitoring of plasma alkaline phosphatases, Calcium, PTH, and creatinine is advised at 6 months intervals(every 3 months for children 1- 2 years) or as indicated [L2347]. Monitoring of urine calcium and phosphate is suggested every 3 months. **Hyperphosphatemia** Fasting serum phosphate level must be followed due to the risk of hyperphosphatemia while taking this drug. To decrease the risk for ectopic mineralization, it is advised that fasting serum phosphate is aimed to be in the lower end of the normal reference range for any given age. Dose interruption and/or dose reduction may be required. Regular measurement of postprandial serum phosphate is advised [L2347]. **Serum parathyroid hormone increases** Increases in serum parathyroid hormone have been measured in some XLH patients while undergoing treatment with burosumab. Regular measurement of serum parathyroid hormone is recommended [L2347]. **Injection site reactions** Administration of burosumab, like other injections, can lead to local injection site reactions. Administration of this drug should cease in any patient experiencing severe injection site reactions and appropriate medical therapy administered [L2347]. **Hypersensitivity** Burosumab should be discontinued if serious hypersensitivity reactions occur and appropriate medical treatment should be provided [L2347]. **Reproductive toxicity/pregnancy** There are no or limited amount of data available from the use of burosumab in pregnant women. Studies in animals have demonstrated reproductive toxicity. Burosumab use is not advised during pregnancy and in women of childbearing potential/age currently not using contraception [L2347]. | Burosumab is composed solely of amino acids and carbohydrates as a native immunoglobulin and is unlikely to be eliminated via hepatic metabolic mechanisms. Its metabolism and elimination are expected to follow the immunoglobulin clearance pathways, resulting in degradation to small peptides and individual amino acids [L2347]. | Burosumab absorption after subcutaneous injection sites into to the blood circulation is nearly complete. Following the subcutaneous route of administration, the time to reach maximum serum concentrations (Tmax) of burosumab is estimated at 5-10 days. The peak serum concentration (Cmax) and area under the concentration-time curve (AUC) of serum burosumab is proportional to the dose, over the dose range of 0.1-2.0 mg/kg [L2347]. | Burosumab is comprised solely of amino acids and carbohydrates as a native immunoglobulin and is not likeluy to be eliminated by hepatic metabolic mechanisms. The metabolism of burosumab and elimination are expected to follow the immunoglobulin clearance pathways, which results in its degradation to smaller peptides and amino acids [L2347]. | The clearance of burosumab depends on weight and is estimated to be 0.290 L/day and 0.136 L/day in a typical adult (70 kg) and pediatric (30 kg) XLH patient, respectively [L2347]. | Drugs Affecting Bone Structure and Mineralization | NA | NA | NA | NA | Fibroblast growth factor 23 | Crysvita | Ultragenyx Pharmaceutical Inc. | Ultragenyx Pharmaceutical Inc. | Subcutaneous | 30 mg/1mL | CRYSVITA is contraindicated:In concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].When serum phosphorus is within or above the normal range for age [see WARNINGS AND PRECAUTIONS].In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism [see Use In Specific Population]. | headache, injection site reaction, vomiting, fever, pain in extremities, decreased vitamin D levels, back pain, tooth infection, restless leg syndrome, dizziness, constipation, and increased blood phosphorus | Crysvita is a monoclonal antibody that targets and blocks the activity of a blood protein called FGF23. In a genetic condition called X-linked hypophosphatemia (HYE-poe-fos-fa-TEEM-ee-a), low phosphate levels in blood are caused by abnormally high levels of FGF23 protein, which causes the kidneys to... | Crysvita is a prescription medicine used to treat the symptoms of X-Linked Hypophosphatemia and Tumor-Induced Osteomalacia. Crysvita may be used alone or with other medications. | NA | Burosumab-twza is a human immunoglobulin G subclass 1 (IgG1), anti-human fibroblast growth factor 23 (FGF23) antibody produced by recombinant DNA technology using Chinese hamster ovary cells. Burosumab-twza is composed of two heavy chain (γ1-chain) molecules and two light chain (τ-chain) molecules. Each heavy chain has an N-linked carbohydrate moiety at asparagine 297 (Asn297). The molecular weight of burosumab-twza determined by mass spectrometry is approximately 147,000. | Link | Link | NA |
| 15404 | Th1594 | Burosumab | >Th1594_Burosumab QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHYMHWVRQAPGQGLEWMGIINPISGSTSNAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDIVDAFDFWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 144100 | C6388H9904N1700O2006S46 | NA | NA | NA | About 19 days [L2347]. | Burosumab (KRN23) is an entirely human monoclonal IgG1 antibody that binds excess fibroblast growth factor 23 (FGF23) and has been successfully tested in clinical trials in children with X-linked hypophosphatemic rickets [A32593]. The U.S. Food and Drug Administration approved Crysvita (burosumab) in April 2018. This is the first drug approved to treat adults and children ages 1 year and older with X-linked hypophosphatemia (XLH), which is a rare, inherited form of rickets. X-linked hypophosphatemia causes low circulating levels of phosphorus in the blood. It causes impaired bone growth and development in children and adolescents and issues with bone mineralization throughout a patient’s life [L2346]. XLH is a serious disease which affects about 3,000 children and 12,000 adults in the United States. Most children with XLH suffer from bowed or bent legs, short stature, bone pain and severe dental pain. Some adults with this condition suffer from persistent, unrelenting discomfort and complications, such as joint pain, impaired mobility, tooth abscesses and hearing loss [L2346]. | This drug is indicated for the treatment of X-linked hypophosphatemia with radiological evidence of bone disease in children of 1 year of age and older and adolescents with growing skeletons [L2347]. | This drug has the ability to reduce the loss of phosphate, to improve pathologically low serum phosphate concentrations and other metabolic changes, as well as to reduce the severity of rickets as seen radiographically [L2348]. In summary, this drug works to support of bone mineralization [L2347]. | Burosumab is a recombinant human monoclonal antibody (IgG1) that both binds to and inhibits the actions of fibroblast growth factor 23 (FGF23). By inhibiting this growth factor, burosumab increases the tubular reabsorption of phosphate from the kidney and thus increases serum concentration of 1, 25 dihydroxy-Vitamin D [L2347]. This form of vitamin D enhances intestinal absorption of phosphate and calcium, supporting bone mineralization [L2351]. | The toxicity of Crysvita can be classified into several categories [L2347]: **Ectopic mineralisation**: Clinically manifested by nephrocalcinosis, has been seen in patients with XLH treated with oral phosphorous and vitamin D analogues. These drugs should be stopped at least 1 week before starting burosumab treatment [L2347]. Monitoring for signs and symptoms of nephrocalcinosis, e.g. by renal ultrasonography, is recommended at the beginning of treatment and at intervals of every 6 months for the first 12 months of treatment, and yearly thereafter. Regular monitoring of plasma alkaline phosphatases, Calcium, PTH, and creatinine is advised at 6 months intervals(every 3 months for children 1- 2 years) or as indicated [L2347]. Monitoring of urine calcium and phosphate is suggested every 3 months. **Hyperphosphatemia** Fasting serum phosphate level must be followed due to the risk of hyperphosphatemia while taking this drug. To decrease the risk for ectopic mineralization, it is advised that fasting serum phosphate is aimed to be in the lower end of the normal reference range for any given age. Dose interruption and/or dose reduction may be required. Regular measurement of postprandial serum phosphate is advised [L2347]. **Serum parathyroid hormone increases** Increases in serum parathyroid hormone have been measured in some XLH patients while undergoing treatment with burosumab. Regular measurement of serum parathyroid hormone is recommended [L2347]. **Injection site reactions** Administration of burosumab, like other injections, can lead to local injection site reactions. Administration of this drug should cease in any patient experiencing severe injection site reactions and appropriate medical therapy administered [L2347]. **Hypersensitivity** Burosumab should be discontinued if serious hypersensitivity reactions occur and appropriate medical treatment should be provided [L2347]. **Reproductive toxicity/pregnancy** There are no or limited amount of data available from the use of burosumab in pregnant women. Studies in animals have demonstrated reproductive toxicity. Burosumab use is not advised during pregnancy and in women of childbearing potential/age currently not using contraception [L2347]. | Burosumab is composed solely of amino acids and carbohydrates as a native immunoglobulin and is unlikely to be eliminated via hepatic metabolic mechanisms. Its metabolism and elimination are expected to follow the immunoglobulin clearance pathways, resulting in degradation to small peptides and individual amino acids [L2347]. | Burosumab absorption after subcutaneous injection sites into to the blood circulation is nearly complete. Following the subcutaneous route of administration, the time to reach maximum serum concentrations (Tmax) of burosumab is estimated at 5-10 days. The peak serum concentration (Cmax) and area under the concentration-time curve (AUC) of serum burosumab is proportional to the dose, over the dose range of 0.1-2.0 mg/kg [L2347]. | Burosumab is comprised solely of amino acids and carbohydrates as a native immunoglobulin and is not likeluy to be eliminated by hepatic metabolic mechanisms. The metabolism of burosumab and elimination are expected to follow the immunoglobulin clearance pathways, which results in its degradation to smaller peptides and amino acids [L2347]. | The clearance of burosumab depends on weight and is estimated to be 0.290 L/day and 0.136 L/day in a typical adult (70 kg) and pediatric (30 kg) XLH patient, respectively [L2347]. | Drugs for Treatment of Bone Diseases | NA | NA | NA | NA | Fibroblast growth factor 23 | Crysvita | Ultragenyx Pharmaceutical Inc. | Ultragenyx Pharmaceutical Inc. | Subcutaneous | 20 mg/1mL | CRYSVITA is contraindicated:In concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].When serum phosphorus is within or above the normal range for age [see WARNINGS AND PRECAUTIONS].In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism [see Use In Specific Population]. | headache, injection site reaction, vomiting, fever, pain in extremities, decreased vitamin D levels, back pain, tooth infection, restless leg syndrome, dizziness, constipation, and increased blood phosphorus | Crysvita is a monoclonal antibody that targets and blocks the activity of a blood protein called FGF23. In a genetic condition called X-linked hypophosphatemia (HYE-poe-fos-fa-TEEM-ee-a), low phosphate levels in blood are caused by abnormally high levels of FGF23 protein, which causes the kidneys to... | Crysvita is a prescription medicine used to treat the symptoms of X-Linked Hypophosphatemia and Tumor-Induced Osteomalacia. Crysvita may be used alone or with other medications. | NA | Burosumab-twza is a human immunoglobulin G subclass 1 (IgG1), anti-human fibroblast growth factor 23 (FGF23) antibody produced by recombinant DNA technology using Chinese hamster ovary cells. Burosumab-twza is composed of two heavy chain (γ1-chain) molecules and two light chain (τ-chain) molecules. Each heavy chain has an N-linked carbohydrate moiety at asparagine 297 (Asn297). The molecular weight of burosumab-twza determined by mass spectrometry is approximately 147,000. | Link | Link | NA |