Teratyde 250 Μg/Ml 250 μg/ml Solution for Injection

TERATYDE is indicated for the treatment of established osteoporosis with or without vertebral fractures in postmenopausal women and primary osteoporosis in men. TERATYDE is indicated for the treatment of osteoporosis associated with sustained systemic glucocorticoid therapy in women and men at increased risk for fracture.

The recommended dose of TERATYDE is 20 u03bcg administered once daily by subcutaneous injection in the thigh or abdomen. The maximum total duration of treatment with TERATYDE should be 24 months (see section 4.4 and 5.1). The 24-month course of TERATYDE should not be repeated over a patientu2019s lifetime. TERATYDE is supplied in a 2,4 ml cartridge contained in a prefilled delivery device (pen) that delivers 20 u03bcg per dose. Patients must be educated to use the proper injection techniques. Please refer to the enclosed User Manual for instructions on the pen injector. Calcium (1 000 mg per day) and Vitamin D (400 - 1 200 IU per day) must be administered concomitantly with TERATYDE.

Special populations

Patients with renal impairment
TERATYDE must not be used in patients with severe renal impairment (see section 4.3.). In patients with moderate renal impairment, TERATYDE should be used with caution. No special caution is required for patients with mild renal impairment.

Patients with hepatic impairment
No data have been reported in patients with impaired hepatic function (see section 5.3). Therefore, TERATYDE should be used with caution.

Paediatric population and young adults with open epiphyses
The safety and efficacy of TERATYDE in children and adolescents less than 18 years has not been established. TERATYDE should not be used in paediatric patients (less than 18 years), or young adults with open epiphyses.

Elderly patients
Dosage adjustment based on age is not required (see section 5.2).

Method of administration
For Subcutaneous use

• TERATYDE should not be used in patients with:
• Hypersensitivity to teriparatide or to any of its excipients listed in section 6.1.
• Hypercalcaemia (see section 4.4).
• Unexplained elevations of alkaline phosphatase.
• Metabolic bone diseases (including hyperparathyroidism and Paget's disease of the bone) other than primary osteoporosis or glucocorticoid-induced osteoporosis (see section 4.4).
• Skeletal malignancies or bone metastases (see section 4.4).
• Patients with prior external beam or implant radiation therapy involving the skeleton should be excluded from treatment with TERATYDE.
• Pregnancy: Safety in pregnancy has not been reported (see section 4.6).
• Lactation: The safety of TERATYDE has not been reported in breastfeeding women (see section 4.6).
• Severe renal impairment

Hypercalcaemia: TERATYDE has not been studied in patients with pre-existing hypercalcaemia. These patients should be excluded from treatment with TERATYDE because of the possibility of exacerbating hypercalcaemia. Hypercalcaemia should be excluded before treatment with TERATYDE. Routine monitoring of serum calcium during therapy is required (see section 4.3).

Bone Disorders other than Osteoporosis: Patients with metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Pagetu2019s disease of the bone) and those with otherwise unexplained elevations of alkaline phosphatase should generally be excluded from treatment with TERATYDE. Patients with skeletal malignancies or bone metastases should also be excluded from treatment with TERATYDE (see section 4.3).

Children: TERATYDE has not been studied in paediatric populations. TERATYDE should not be used in paediatric patients or young adults with open epiphyses. Experience in the younger adult population, including premenopausal women, is limited. Women of childbearing potential should use effective methods of contraception during use of teriparatide. If pregnancy occurs, teriparatide should be discontinued.

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

Hypotension: In reported short-term clinical studies with teriparatide, isolated episodes of transient orthostatic hypotension were observed (see section 4.7). Typically, it was reported that 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.

Carcinogenesis: In reported studies where rats were treated with near-lifetime daily teriparatide injections had dose-dependent exaggerated bone formation and increased incidence of osteosarcoma. Teriparatide did not increase the incidence of neoplasms in other tissues. A reported second rat study (of up to 2 years duration) confirmed that the occurrence of osteosarcoma was dependent upon dose and duration of treatment. A no-observed-effect level (NOEL) was reported; the NOEL is 3 times the exposure in patients given a 20 u03bcg dose based upon AUC. Until further reported clinical data become available, the recommended treatment duration of 24 months should not be exceeded.

Mutagenesis: Teriparatide was found in reported studies to not be genotoxic in any of the following test systems: The Ames test for bacterial mutagenesis with and without metabolic activation, the mouse lymphoma assay for mammalian cell mutation, the chromosomal aberration assay in Chinese hamster ovary cells and the in vivo micronucleus test in mice. The relevance of these findings to humans is not known: Osteosarcoma has not been reported in teriparatide clinical studies. Chronic elevation of blood PTH levels as occurs clinically in primary or secondary hyperparathyroidism is not associated with an increased risk of osteosarcoma.

Renal impairment: Caution should be exercised in patients with moderate renal impairment.

Teriparatide has been evaluated in reported pharmacodynamic interaction studies with hydrochlorothiazide, furosemide, atenolol and extended release preparations of diltiazem, nifedipine, felodipine, nisoldipine. No clinically significant interactions were reported. 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.

Serum Calcium: TERATYDE can induce small, transient increases in serum calcium. If serum calcium is to be assessed, blood samples should be obtained at least 16 hours after the most recent TERATYDE injection to allow waning of the effects of the administered teriparatide.

Urinary Calcium: 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 reported clinical trials.

Digoxin: In a reported study of 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 reported that hypercalcaemia may predispose patients to digitalis toxicity. Because teriparatide transiently increases serum calcium, teriparatide should be used with caution in patients taking digitalis.

Women of childbearing potential / Contraception in females: Women of childbearing potential should use effective methods of contraception during use of TERATYDE. If pregnancy occurs, TERATYDE should be discontinued.

Pregnancy: Animal reproduction studies have shown no teratogenic effects with teriparatide. (see section 5.3). The effect of TERATYDE treatment on human foetal development has not been reported. Teriparatide should not be administered to pregnant women (see section 4.3).

Breastfeeding: There have been no reported studies to determine if teriparatide is secreted into breast milk. Teriparatide should not be administered to nursing women (see section 4.3).

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

TERATYDE may cause orthostatic hypotension or dizziness. These patients should refrain from driving or the use of machines until symptoms have subsided.

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

System organ class Frequent Less frequent

Blood and lymphatic system disorders Anaemia -

Immune System Disorder - Anaphylaxis

Metabolism and nutrition disorders Hypercholesterolaemia Hypercalcaemia greater than 2.76 mmol/L, hyperuricemia,

Psychiatric disorders Depression -

Nervous system disorders Dizziness, headache, sciatica, syncope -

Ear and labyrinth disorders Vertigo -

Cardiac disorders Palpitations Tachycardia

Vascular disorders Hypotension -

Respiratory, thoracic and mediastinal disorders Dyspnoea Emphysema

Gastrointestinal disorders Nausea, vomiting, hiatus hernia, gastroesophageal reflux disease Haemorrhoids

Skin and subcutaneous tissue disorders Increased sweating -

Musculoskeletal and connective tissue disorders Pain in limb Muscle cramps Myalgia, arthralgia, back cramp/pain*

Renal and urinary disorders - Urinary incontinence, polyuria, micturition urgency, nephrolithiasis, Renal failure/impairment

General disorders and administration site conditions Fatigue, chest pain, asthenia, mild and transient injection site events, including pain, swelling, erythema, localised bruising, pruritis and minor bleeding at injection site. Injection site erythema, injection site reaction

Possible allergic events soon after injection: acute dyspnoea, oro/facial oedema, generalised urticaria, chest pain, oedema (mainly peripheral).

Investigations - Weight increased, cardiac murmur, alkaline phosphatase increase

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

Description of selected adverse reactions In a reported clinical trial, antibodies that cross-reacted with teriparatide were detected in 2.8 % of women receiving teriparatide. Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy. There was no reported evidence of hypersensitivity reactions, allergic reactions, effects on serum calcium, or effects on Bone Mineral Density (BMD) response. In reported clinical trials, the following reactions were reported at a u2265 1 % difference in frequency from placebo: vertigo, nausea, pain in limb, dizziness, depression, dyspnoea.

Teriparatide increases serum uric acid concentrations. In reported 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.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of PATRAM is important. It allows continued monitoring of the benefit/risk balance of PATRAM. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: Suspected adverse reactions can also be reported directly to the HCR via email: [email protected] or Tel: +27(0) 12 643 2000

Signs and symptoms
The effects of overdose that might be expected include a delayed hypercalcaemic effect and risk of orthostatic hypotension. Nausea, vomiting, dizziness and headache might also occur.

Overdose management
There is no specific antidote for TERATYDE. Treatment of suspected overdose should include transitory discontinuation of TERATYDE, monitoring of serum calcium, and implementation of appropriate supportive measures, such as hydration.