Teriparatide

Important Safety Information

In male and female rats, Teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to Teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, prescribe Teriparatide only for patients for whom the potential benefits are considered to outweigh the potential risk. Teriparatide should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy involving the skeleton)

Two carcinogenicity bioassays were conducted in Fischer 344 rats. In these studies, rats were given daily subcutaneous Teriparatide injections at doses that resulted in systemic exposures between 3 and 60 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 mcg (based on AUC comparison). Teriparatide treatment resulted in increases in the incidence of bone tumors, including osteosarcoma, that occurred in association with dose-dependent exaggerated increases in bone mass. The studies showed that the occurrence of bone tumors was dependent upon dose and duration of exposure. The clinical significance of the observations in rats has not been established. Osteosarcoma has not been observed in Teriparatide clinical trials.

The safety and efficacy of Teriparatide (rDNA origin) injection have not been evaluated beyond 2 years (median 19 months in women and 10 months in men). Consequently, the maximum lifetime exposure to Teriparatide for an individual patient is 18 months. In clinical trials, the frequency of urolithiasis was similar in patients treated with Teriparatide and placebo. However, Teriparatide has not been studied in patients with active urolithiasis. If active urolithiasis or pre-existing hypercalciuria are suspected, measurement of urinary calcium excretion should be considered. Teriparatide should be used with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

In short-term clinical studies with Teriparatide, isolated episodes of transient orthostatic hypotension were observed. Typically, an event began within 4 hours of dosing and spontaneously resolved within a few minutes to a few hours. When transient orthostatic hypotension occurred, it happened within the first several doses, was relieved by placing subjects in a reclining position and did not preclude continued treatment. Patients experiencing symptoms associated with hypotension should not drive or operate machinery until they become asymptomatic.

Pregnant women and women of childbearing potential: Teriparatide should not be administered to women who are pregnant. The effect of Teriparatide treatment on human fetal development has not been studied. Women of childbearing potential should use effective methods of contraception during use of Teriparatide. Should pregnancy occur, Teriparatide should be discontinued (see Contraindications).
Nursing women: There have been no clinical studies to determine ifTeriparatide is secreted into breast milk. Teriparatide should not be administered to nursing mothers (see Contraindications).
Pediatrics: Teriparatide has not been studied in pediatric populations. Teriparatide should not be used in children or young adults with open epiphyses (see Contraindications).
Premenopausal women: Before initiating therapy with Teriparatide in premenopausal women with glucocorticoid-induced Osteoporosis, risk factors such as low BMD, length and dosage of glucocorticoid therapy, previous fractures, family history, high bone turnover, level of underlying disease activity, low sex steroid level or low body mass index, should be considered