TERIPARATIDE AMBIO PHARMA

Summary of the safety profile The most commonly reported adverse reactions in patients treated with teriparatide are nausea, pain in limb, headache and dizziness. 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 post- marketing 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). 25 mmol/ Psychiatric disorders Common: Depression Nervous system disorders Common: Dizziness, headache, sciatica, syncope Ear and labyrinth disorders Common: Vertigo Cardiac disorders Common: Palpitations Uncommon: Tachycardia Vascular disorders Common: Hypotension Respiratory, thoracic and mediastinal disorders Common: Dyspnoea Uncommon: Emphysema Gastrointestinal disorders Common: Nausea, vomiting, hiatus hernia, gastroesophageal reflux disease Uncommon: Haemorrhoids Skin and subcutaneous tissue disorders Common: Sweating increased Musculoskeletal and connective tissue disorders Very common: Pain in limb Common: Muscle cramps Uncommon: Myalgia, arthralgia, back cramp/pain* Renal and urinary disorders Uncommon: Urinary incontinence, polyuria, micturition urgency, nephrolithiasis Rare: Renal failure/impairment General disorders and administration site conditions Common: Fatigue, chest pain, asthenia, mild and transient injection site events, including pain, swelling, erythema, localised bruising, pruritis and minor bleeding at injection site.

Uncommon:

Injection site erythema, injection site reaction Rare: Possible allergic events soon after injection: acute dyspnoea, oro/facial oedema, generalised urticaria, chest pain, oedema (mainly peripheral) Investigations Uncommon: 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 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.

7% of placebo patients. However, the hyperuricemia did not result in an increase in gout, arthralgia, or urolithiasis. 8% of women receiving teriparatide. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen injection.

Routine calcium monitoring during therapy is not required. Teriparatide Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen 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 Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen has not been studied in patients with active urolithiasis. Teriparatide Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen 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 studies with Teriparatide Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen 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.

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 Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen.

If pregnancy occurs, Teriparatide Ambio Pharma 20 microgram / 80 microliter, solution for injection in pre-filled pen should be discontinued. 3). Until further clinical data become available, the recommended treatment time of 24 months should not be exceeded.

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium free”.

1. 6) • Pre-existing hypercalcaemia • Severe renal impairment • Metabolic bone diseases (including hyperparathyroidism and Paget’s disease of the bone) other than primary osteoporosis or glucocorticoid-induced osteoporosis. • Unexplained elevations of alkaline phosphatase • Prior external beam or implant radiation therapy to the skeleton • Patients with skeletal malignancies or bone metastases should be excluded from treatment with teriparatide.