SONDELBAY Solution for injection Ref.[50037] Active ingredients: Teriparatide

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Serum and urine calcium

In normocalcaemic patients, slight and transient elevations of serum calcium concentrations have been observed following teriparatide injection. Serum calcium concentrations reach a maximum between 4 and 6 hours and return to baseline by 16 to 24 hours after each dose of teriparatide. Therefore, if blood samples for serum calcium measurements are taken, this should be done at least 16 hours after the most recent teriparatide injection. Routine calcium monitoring during therapy is not required.

Teriparatide may cause small increases in urinary calcium excretion, but the incidence of hypercalciuria did not differ from that in the placebo-treated patients in clinical trials.

Urolithiasis

Teriparatide has not been studied in patients with active urolithiasis. Sondelbay should be used with caution in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

Orthostatic hypotension

In short-term clinical trials 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.

Renal impairment

Caution should be exercised in patients with moderate renal impairment.

Younger adult population

Experience in the younger adult population (>18 to 29 years), including premenopausal women, is limited (see section 5.1). Treatment should only be initiated if the benefit clearly outweighs risks in this population.

Women of childbearing potential should use effective methods of contraception during use of teriparatide. If pregnancy occurs, Sondelbay should be discontinued.

Duration of treatment

Studies in rats indicate an increased incidence of osteosarcoma with long-term administration of teriparatide (see section 5.3). Until further clinical data become available, the recommended treatment time of 24 months should not be exceeded.

Excipient

This medicinal product contains less than 1 mmol sodium (23 mg) per dose unit, that is to say essentially ‘sodium-free’.

In a study of 15 healthy subjects administered digoxin daily to steady state, a single teriparatide dose did not alter the cardiac effect of digoxin. However, sporadic case reports have suggested that hypercalcaemia may predispose patients to digitalis toxicity. Because teriparatide transiently increases serum calcium, teriparatide should be used with caution in patients taking digitalis.

Teriparatide has been evaluated in pharmacodynamic interaction studies with hydrochlorothiazide. No clinically significant interactions were noted.

Co-administration of raloxifene or hormone replacement therapy with teriparatide did not alter the effects of teriparatide on serum or urine calcium or on clinical adverse events.

Women of childbearing potential / Contraception in females

Women of childbearing potential should use effective methods of contraception during use of teriparatide. If pregnancy occurs, Sondelbay should be discontinued.

Pregnancy

Sondelbay is contraindicated for use during pregnancy (see section 4.3).

Breast-feeding

Sondelbay is contraindicated for use during breast-feeding. It is not known whether teriparatide is excreted in human milk.

Fertility

Studies in rabbits have shown reproductive toxicity (see section 5.3). The effect of teriparatide on human foetal development has not been studied. The potential risk for humans is unknown.

Teriparatide has no or negligible influence on the ability to drive and use machines. Transient, orthostatic hypotension or dizziness was observed in some patients. These patients should refrain from driving or the use of machines until symptoms have subsided.

Summary of the safety profile

The most commonly reported adverse reactions in patients treated with teriparatide are nausea, pain in limb, headache and dizziness.

Tabulated list of adverse reactions

Of patients in the teriparatide trials, 82.8% of the teriparatide patients and 84.5% of the placebo patients reported at least 1 adverse event. The adverse reactions associated with the use of teriparatide in osteoporosis clinical trials and postmarketing exposure are summarised in the table below. The following convention has been used for the classification of the adverse reactions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) very rare (<1/10,000).

Table 1. Adverse drug reactions:

^* Serious cases of back cramp or pain have been reported within minutes of the injection.

Description of selected adverse reactions

In clinical trials the following reactions were reported at a ≥1% difference in frequency from placebo: vertigo, nausea, pain in limb, dizziness, depression, dyspnoea.

Teriparatide increases serum uric acid concentrations. In clinical trials, 2.8% of teriparatide patients had serum uric acid concentrations above the upper limit of normal compared with 0.7% of placebo patients. However, the hyperuricemia did not result in an increase in gout, arthralgia, or urolithiasis.

In a large clinical trial, for another teriparatide product antibodies that cross-reacted with that teriparatide product were detected in 2.8% of women. Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy. There was no evidence of hypersensitivity reactions, allergic reactions, effects on serum calcium, or effects on Bone Mineral Density (BMD) response.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.