Consumer medicine information

1 Name of Medicine

Teriparatide.

2 Qualitative and Quantitative Composition

One pre-filled pen of Teriparatide Lupin of 2.4 mL contains 600 microgram of teriparatide (corresponding to 250 microgram per mL).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Teriparatide Lupin is a sterile, colourless, clear, isotonic solution in pre-filled pens.

4 Clinical Particulars

4.9 Overdose

No cases of overdose were reported during clinical trials. Teriparatide has been safely administered in single doses of up to 100 microgram. In a clinical study, doses of 60 microgram/day for 6 weeks were safely tolerated. The effects of overdose that might be expected include delayed hypercalcaemia and risk of orthostatic hypotension. Nausea, vomiting, dizziness and headache might also occur.
In post-marketing spontaneous reports, there have been cases of medication error in which the entire contents (up to 800 microgram) of the teriparatide pen have been administered as a single dose. Transient events reported have included nausea, weakness/ lethargy and hypotension. In some cases, no adverse events occurred as a result of the overdose. No fatalities associated with overdose have been reported.
In single-dose rodent studies using subcutaneous injection of teriparatide, no mortality was seen in rats given doses of 1000 microgram/kg (526 times the human dose based on body surface area) or in mice given 10,000 microgram/kg (2,635 times the human dose).
Overdose management. There is no specific antidote for teriparatide. Treatment of suspected overdose should include discontinuation of teriparatide, monitoring of serum calcium, and implementation of appropriate supportive measures, such as hydration.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Teriparatide was not genotoxic in assays for gene mutations (Ames test and mouse lymphoma assay in vitro) and chromosomal damage (Chinese hamster ovary cells in vitro and the mouse micronucleus test in vivo).
Carcinogenicity. Two carcinogenicity bioassays were conducted in rats. In the first study, male and female rats were given daily subcutaneous teriparatide injections of 5, 30, or 75 microgram/kg/day for 24 months from 2 months of age. These doses resulted in systemic exposures that were, respectively, 3, 20, and 60 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 microgram (based on AUC comparison). Teriparatide treatment resulted in a marked dose-related increase in the incidence of osteosarcoma, a rare malignant bone tumour, in both male and female rats. Osteosarcomas were observed at all doses, occurred after 17 to 20 months of treatment, and reached an incidence of 38% to 52% in the high-dose groups. Teriparatide also caused increased incidences of osteoblastoma and osteoma in both sexes. No osteosarcomas, osteoblastomas or osteomas were observed in untreated control rats. The bone tumours in rats occurred in association with a large increase in bone mass and focal osteoblast hyperplasia.
The second 2-year study was carried out in order to determine the effect of treatment duration and animal age on the development of bone tumours. Female rats were treated for different periods between 2 and 26 months of age with subcutaneous doses of 5 and 30 microgram/kg (equivalent to 3 and 20 times the human exposure at the 20 microgram dose, based on AUC). The study showed that the occurrence of osteosarcoma, osteoblastoma and osteoma was dependent upon dose and duration of exposure. Bone tumours were observed when immature 2-month old rats were treated with 30 microgram/kg/day for 6 or 24 months. Bone tumours were also observed when mature 6-month old rats were treated with 30 microgram/kg/day for 6 or 20 months. Tumours were not detected when mature 6-month old rats were treated with 5 microgram/kg/day for 6 or 20 months. The results did not demonstrate a difference in susceptibility to bone tumour formation, associated with teriparatide treatment, between mature and immature rats. The relevance of these rat findings to humans is uncertain.
No bone neoplasms or preneoplastic lesions were found in monkeys treated with teriparatide SC for 18 months, and then observed for a further 3 years, at a dose yielding 5-fold clinical exposure levels (based on AUC data).

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure. Teriparatide, synthetically derived, is identical to the 34 N-terminal amino acid sequence of endogenous human parathyroid hormone.
Teriparatide is a polypeptide which molecular weight, molecular formula and molecular structure are as follows.
Molecular weight: 4117.72 g/mol (average mass of the isotopes).
Molecular formula: C₁₈₁H₂₉₁N₅₅O₅₁S₂ (as free base).
Molecular structure:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSTEPATI.gif CAS number. The CAS number for teriparatide is 52232-67-4.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes

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