4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Added:
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
Added (bold text):
The maximum total duration of treatment with FORSTEO should be 18 months (see section 4.4). The 18-month course of FORSTEO should not be repeated over a patient’s lifetime.
4.3 Contraindications
Added (New Bullet):
· Pregnancy and lactation (see section 4.4 and 4.6)
4.4 Special warnings and precautions for use
Added:
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.
4.6 Pregnancy and lactation
Deleted:
The potential risk for humans is unknown. Given the indication, FORSTEO should not be used during pregnancy or by breast-feeding women.
Added:
General recommendation
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.
It is not known whether teriparatide is excreted in human milk.
FORSTEO is contraindicated for use during pregnancy or breast-feeding.
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.
Added (bold text):
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System Organ Class
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Adverse reactions
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General Disorders and Administration Site Conditions
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Rare: Possible allergic events soon after injection: acute dyspnoea, oro/facial oedema, generalized urticaria, chest pain, oedema (mainly peripheral).
Common: Mild and transient injection site events, including pain, swelling, erythema, localised bruising, pruritis and minor bleeding at injection site.
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Metabolism and Nutrition Disorders
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Uncommon: Hypercalcemia greater than 2.76 mmol/l (11mg/dl).
Rare: Hypercalcemia greater than 3.25 mmol/l (13mg/dl).
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Musculoskeletal and Connective Tissue and Bone Disorders
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Uncommon: myalgia, arthralgia,
Not known: Back cramp/pain*
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Investigations
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Uncommon: alkaline phosphatase increase
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* Serious cases of back cramp or pain have been reported within minutes of the injection.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Added:
Clinical efficacy
Risk Factors
Premenopausal women with glucocorticoid-induced osteoporosis should be considered at high risk for fracture if they have a prevalent fracture or a combination of risk factors that place them at high risk for fracture (e.g., low bone density [e.g., T score ≤−2], sustained high dose glucocorticoid therapy [e.g., ≥7.5 mg/day for at least 6 months], high underlying disease activity, low sex steroid levels).
Glucocorticoid-induced osteoporosis
The efficacy of Forsteo in men and women (N=428) receiving sustained systemic glucocorticoid therapy (equivalent to 5 mg or greater of prednisone for at least 3 months) was demonstrated in an 18-month, randomised, double-blind, comparator-controlled study (alendronate 10 mg/day). Twenty-eight percent of patients had one or more radiographic vertebral fractures at baseline. All patients were offered 1000 mg calcium per day and 800 IU vitamin D per day.
This study included postmenopausal women (N=277), premenopausal women (N=67), and men (N=83). At baseline, the postmenopausal women had a mean age of 61 years, mean lumbar spine BMD T score of −2.7, median prednisone equivalent dose of 7.5 mg/day, and 34% had one or more radiographic vertebral fractures; premenopausal women had a mean age of 37 years, mean lumbar spine BMD T score of −2.5, median prednisone equivalent dose of 10 mg/day, and 9% had one or more radiographic vertebral fractures; and men had a mean age of 57 years, mean lumbar spine BMD T score of −2.2, median prednisone equivalent dose of 10 mg/day, and 24% had one or more radiographic vertebral fractures.
Sixty-nine percent of patients completed the 18-month study. At endpoint, FORSTEO significantly increased lumbar spine BMD (7.2%) compared with alendronate (3.4%) (p<0.001). FORSTEO increased BMD at the total hip (3.6%) compared with alendronate (2.2%) (p<0.01), as well as at the femoral neck (3.7%) compared with alendronate (2.1%) (p<0.05).
A preliminary analysis of 336 spinal X-rays showed that 10 patients in the alendronate group (6.1%) had experienced a new vertebral fracture compared with 1 patient in the FORSTEO group (0.6%). In addition, 9 patients in the alendronate group (4.2%) had experienced a nonvertebral fracture compared with 12 patients in the FORSTEO group (5.6%).
In premenopausal women, the increase in BMD from baseline to endpoint was significantly greater in the FORSTEO group compared with the alendronate group at the lumbar spine (4.2% versus −1.9%; p<0.001) and total hip (3.8% versus 0.9%; p=0.005). However, no significant effect on fracture rates was demonstrated.
5.3 Preclinical safety data
Added (bold text):
Teriparatide was not genotoxic in a standard battery of tests. It produced no teratogenic effects in rats, mice or rabbits. There were no important effects observed in pregnant rats or mice administered teriparatide at daily doses of 30 to 1000 mcg/kg. However, foetal resorption and reduced litter size occurred in pregnant rabbits administered daily doses of 3 to 100 mcg/kg. The embryotoxicity observed in rabbits may be related to their much greater sensitivity to the effects of PTH on blood ionised calcium compared with rodents.
10. DATE OF REVISION OF THE TEXT
New date
02 April 2008