4.1. Therapeutic indications

FORSTEO is indicated in adults.

Treatment of osteoporosis in postmenopausal women and in men at increased risk of fracture (see section 5.1). In postmenopausal women, a significant reduction in the incidence of vertebral and non-vertebral fractures but not hip fractures has been demonstrated.

Treatment of osteoporosis associated with sustained systemic glucocorticoid therapy in women and men at increased risk for fracture (see section 5.1).

4.2. Posology and method of administration

Posology

The recommended dose of FORSTEO is 20 micrograms administered once daily.

The maximum total duration of treatment with FORSTEO should be 24 months (see section 4.4). The 24-month course of FORSTEO should not be repeated over a patient's lifetime.

Patients should receive supplemental calcium and vitamin D supplements if dietary intake is inadequate.

Following cessation of FORSTEO therapy, patients may be continued on other osteoporosis therapies.

Special populations

Patients with renal impairment

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

Patients with hepatic impairment

No data are available in patients with impaired hepatic function (see section 5.3). Therefore, FORSTEO should be used with caution.

Paediatric population and young adults with open epiphyses

The safety and efficacy of FORSTEO in children and adolescents less than 18 years has not been established. FORSTEO 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

FORSTEO should be administered once daily by subcutaneous injection in the thigh or abdomen.

Patients must be trained to use the proper injection techniques (see section 6.6). A user manual is also available to instruct patients on the correct use of the pen.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Pregnancy and breast-feeding (see sections 4.4 and 4.6)

• Pre-existing hypercalcaemia

• Severe renal impairment

• Metabolic bone diseases (including hyperparathyroidism and Paget's disease of the bone) other than primary osteoporosis or glucorticoid-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.

4.4. Special warnings and precautions for use

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 FORSTEO injection. Routine calcium monitoring during therapy is not required.

FORSTEO 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

FORSTEO has not been studied in patients with active urolithiasis. FORSTEO 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 FORSTEO, 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, 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 FORSTEO. If pregnancy occurs, FORSTEO 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.

Sodium content

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

4.5. Interaction with other medicinal products and other forms of interaction

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

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

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

4.6. Fertility, pregnancy and lactation

Women of childbearing potential / Contraception in females

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

Pregnancy

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

Breast-feeding

FORSTEO 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.

4.7. Effects on ability to drive and use machines

FORSTEO 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.

4.8. Undesirable effects

Summary of the safety profile

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

Tabulated list of adverse reactions

Of patients in the teriparatide trials, 82.8 % of the FORSTEO 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 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).

Blood and lymphatic system disorders

Common: Anaemia

Immune System Disorder

Rare: Anaphylaxis

Metabolism and nutrition disorders

Common: Hypercholesterolaemia

Uncommon: Hypercalcaemia greater than 2.76 mmol/L, hyperuricemia

Rare: Hypercalcaemia greater than 3.25 mmol/L

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.

FORSTEO increases serum uric acid concentrations. In clinical trials, 2.8 % of FORSTEO 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, antibodies that cross-reacted with teriparatide were detected in 2.8 % of women receiving FORSTEO. 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 Yellow Card Scheme; Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Signs and symptoms

FORSTEO has been administered in single doses of up to 100 micrograms and in repeated doses of up to 60 micrograms/day for 6 weeks.

The effects of overdose that might be expected include delayed hypercalcaemia and risk of orthostatic hypotension. Nausea, vomiting, dizziness, and headache can also occur.

Overdose experience based on post-marketing spontaneous reports

In post-marketing spontaneous reports, there have been cases of medication error where the entire contents (up to 800 mcg) 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.

Overdose management

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