TYMLOS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TYMLOS (TYMLOS).
Selective parathyroid hormone receptor agonist; stimulates osteoblast activity to increase bone formation and remodeling, leading to improved bone microarchitecture and density.
| Metabolism | Not extensively metabolized; eliminated via proteolytic degradation in the liver and other tissues. |
| Excretion | Renal (approximately 99% of absorbed dose excreted as inactive metabolites in urine), biliary/fecal (minimal, <1%) |
| Half-life | Terminal elimination half-life is approximately 30 minutes for the intact peptide; provides rapid clearance after subcutaneous administration, minimizing systemic accumulation. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Approximately 1.2 L/kg, indicating distribution beyond extracellular fluid into tissues. |
| Bioavailability | Subcutaneous: Approximately 40% bioavailability relative to intravenous administration. |
| Onset of Action | Subcutaneous: Onset of bone turnover marker changes (e.g., P1NP increase) detectable within 2-4 weeks; clinical fracture risk reduction seen after 12-18 months. |
| Duration of Action | Subcutaneous: Effects on bone formation markers (P1NP) peak at 3-6 months, decline thereafter; treatment duration is limited to 18 months due to theoretical risk of osteosarcoma in clinical trials. |
80 mcg subcutaneously once daily.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; insufficient data for GFR <30 mL/min. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No dose adjustment required based on age; consider renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TYMLOS (TYMLOS).
| Breastfeeding | Lactation Summary: It is unknown if abaloparatide is excreted in human milk, affects milk production, or affects the breastfed infant. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. The M/P ratio is not established. |
| Teratogenic Risk | Teratogenic Risk Profile: TYMLOS (abaloparatide) is classified as Pregnancy Category C. Animal studies in rats and rabbits have shown fetal toxicity including skeletal abnormalities and decreased fetal weight at doses 3-20 times the human exposure. There are no adequate and well-controlled studies in pregnant women. The drug should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. First trimester: unknown risk; second and third trimesters: potential for fetal musculoskeletal abnormalities. |
■ FDA Black Box Warning
TYMLOS caused a dose-dependent increase in the incidence of osteosarcoma in male and female rats. The clinical relevance of this finding is unknown. Prescribe only for patients for whom the potential benefits are considered to outweigh the potential risk. Avoid use in patients at increased baseline risk for osteosarcoma (e.g., Paget's disease of bone, uncharacterized skeletal abnormalities, prior external beam or implant radiation therapy, or with open epiphyses).
| Serious Effects |
["Pre-existing hypercalcemia","History of skeletal malignancy or other bone metastases","Paget's disease of bone","Unexplained elevations of alkaline phosphatase","Prior external beam or implant radiation therapy to the skeleton","Open epiphyses (skeletally immature patients)","Hypersensitivity to TYMLOS or any of its components"]
| Precautions | ["Risk of osteosarcoma (see boxed warning)","Serum calcium: May cause hypercalcemia; monitor calcium levels and avoid in patients with pre-existing hypercalcemia","Risk of hypotension, including orthostatic hypotension; monitor blood pressure","Potential for urolithiasis in susceptible individuals","Bone safety: The safety and efficacy of treatment for more than 2 years have not been established; cumulative use beyond 2 years is not recommended"] |
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| Fetal Monitoring | Maternal-Fetal Monitoring: Monitor serum calcium levels periodically during treatment as TYMLOS may cause hypercalcemia. Assess renal function. No specific fetal monitoring is recommended unless clinical signs warrant; however, routine prenatal care should be maintained. |
| Fertility Effects | Fertility Effects: In animal studies, abaloparatide did not impair fertility in male or female rats at doses up to 100 times the human exposure. There are no human data on fertility effects. |