Medicinal product no longer authorised
Medicinal product no longer authorised
Forcaltonin 100 IU solution for injection
One ampoule of Forcaltonin 100 IU contains 100 International Units (IU) corresponding to approximately 15 micrograms recombinant salmon calcitonin (produced by recombinant DNA technology in Escherichia coli) in 1 ml of an acetate buffer. For excipients, see section 6.1.
Solution for injection Clear colourless solution
Calcitonin is indicated for:
Prevention of acute bone loss due to sudden immobilisation such as in patients with recent osteoporotic fractures
Paget's disease
Hypercalcaemia of malignancy
For subcutaneous, intramuscular or intravenous infusion (product specific) use in individuals aged 18 years or more. Salmon calcitonin may be administered at bedtime to reduce the incidence of nausea or vomiting which may occur, especially at the initiation of therapy.
Prevention of acute bone loss:
The recommended dosage is 100 I.U. daily or 50 I.U. twice daily for 2 to 4 weeks, administered subcutaneously or intramuscularly. The dose may be reduced to 50 I.U. daily at the start of remobilisation. The treatment should be maintained until patients are fully mobilized.
Paget's disease:
The recommended dosage is 100 IU per day administered subcutaneously or intramuscularly, however, a minimum dosage regimen of 50 IU three times a week has achieved clinical and biochemical improvement. Dosage is to be adjusted to the individual patient's needs. The duration of treatment depends on the indication for treatment and the patient's response. The effect of calcitonin may be monitored by measurement of suitable markers of bone remodeling, such as serum alkaline
Medicinal product no longer authorised
phosphatase or urinary hydroxyproline or deoxypyridinoline. The dose may be reduced after the condition of the patient has improved.
Hypercalcemia of malignancy:
The recommended starting dose is 100 IU every 6 to 8 hours by subcutaneous or intramuscular injection. In addition, salmon calcitonin could be administered by intravenous injection after previous rehydration. If the response is not satisfactory after one or two days, the dose may be increased to a maximum of 400 IU every 6 to 8 hours. In severe or emergency cases, intravenous infusion with up to 10 IU/kg body weight in 500ml 0.9% w/v sodium chloride solution may be administered over a period of at least 6 hours.
Experience with the use of calcitonin in the elderly has shown no evidence of reduced tolerability or altered dosage requirements. The same applies to patients with altered hepatic function. The metabolic clearance is much lower in patients with end-stage renal failure than in healthy subjects. However, the clinical relevance of this finding is not known (see section 5.2)
Hypersensitivity to the active substance or to any of the excipients. Calcitonin is also contraindicated in patients with hypocalcaemia.
Because calcitonin is a peptide, the possibility of systemic allergic reactions exists and allergic-type reactions including isolated cases of anaphylactic shock have been reported in patients receiving calcitonin. Such reactions should be differentiated from generalised or local flushing, which are common non-allergic effects of calcitonin (see 4.8). Skin testing should be conducted in patients with suspected sensitivity to calcitonin prior to their treatment with calcitonin. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially sodium free.
Serum calcium levels may be transiently decreased to below normal levels following administration of calcitonin, notably upon initiation of therapy in patients with abnormally high rates of bone turnover. This effect is diminished as osteoclastic activity is reduced. However, care should be exercised in patients receiving concurrent treatment with cardiac glycosides or calcium channel blocking agents. Dosages of these drugs may require adjustment in view of the fact that their effects may be modified by changes in cellular electrolyte concentrations. The use of calcitonin in combination with bisphosphonates may result in an additive calcium-lowering effect.
Calcitonin has not been studied in pregnant women. Calcitonin should be used during pregnancy only if treatment is considered absolutely essential by the physician.
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It is not known if the substance is excreted in human milk. In animals, salmon calcitonin has been shown to decrease lactation and to be excreted in milk (see 5.3). Therefore, breast-feeding is not recommended during treatment.
No data exist on the effects of injectable calcitonin on the ability to drive and use machines. Injectable calcitonin may cause transient dizziness (see 4.8. Undesirable effects) which may impair the reaction of the patient. Patients must therefore be warned that transient dizziness may occur, in which case they should not drive or use machines.
Frequency categories: Very common ( >1/10); common (>1/100, <1/10); uncommon (>1/1,000, < 1/100); rare (>1/10,000, < 1/1,000); very rare (<1/10,000), including isolated reports.
Gastrointestinal disorder:
Very common:Nausea with or without vomiting is noted in approximately 10% of patients treated with calcitonin. The effect is more evident on initiation of therapy and tends to decrease or disappear with continued administration or a reduction in dose. An antiemetic may be administered, if required. Nausea/vomiting are less frequent when the injection is done in the evening and after meals. Uncommon:diarrhea
Vascular disorders:
Very common:Skin flushes (facial or upper body). These are not allergic reactions but are due to a pharmacological effect, and are usually observed 10 to 20 minutes after administration.
General disorders and administration site conditions
Uncommon
: local inflammatory reactions at the site of subcutaneous or intramuscular injection
Skin and subcutaneous tissue disorders
Uncommon:
skin rash
Nervous system disorders:
Uncommon:
metallic taste in the mouth; dizziness
Renal and urinary disorders:
Uncommon:
diuresis
Metabolic and nutrition disorders:
Rare:In case of patients with high bone remodelling (Paget's disease and young patients) a transient decrease of calcaemia may occur between the 4th and the 6th hour after administration, usually asymptomatic
Investigations:
Rare:
Neutralising antibodies to calcitonin rarely develop. The development of these antibodies is not usually related to loss of clinical efficacy, although their presence in a small percentage of patients following long-term therapy with calcitonin may result in a reduced response to the product. The presence of antibodies appears to bear no relationship to allergic reactions, which are rare. Calcitonin receptor down-regulation may also result in a reduced clinical response in a small percentage of patients following long-term therapy.
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Immune system disorders:
Very rare
: serious allergic-type reactions, such as bronchospasm, swelling of the tongue and throat, and in isolated cases, anaphylaxis.
Nausea, vomiting, flushing and dizziness are known to be dose dependent when calcitonin is administered parenterally. Single doses (up to 10,000 I.U.) of injectable salmon calcitonin have been administered without adverse reactions, other than nausea and vomiting, and exacerbation of pharmacological effects. Should symptoms of overdose appear, treatment should be symptomatic.
Pharmacotherapeutic group: antiparathyroid hormone, ATC code: H05BA01 (calcitonin, salmon). The pharmacological properties of the synthetic and recombinant peptides have been demonstrated to be qualitatively and quantitatively equivalent. Calcitonin is a calciotropic hormone, which inhibits bone resorption by a direct action on osteoclasts. By inhibiting osteoclast activity via its specific receptors, salmon calcitonin decreases bone resorption. In pharmacological studies, calcitonin has been shown to have analgesic activity in animal models. Calcitonin markedly reduces bone turnover in conditions with an increased rate of bone resorption such as Paget 's disease and acute bone loss due to sudden immobilisation. The absence of mineralisation defect with calcitonin has been demonstrated by bone histomorphometric studies both in man and in animals. Decreases in bone resorption as judged by a reduction in urinary hydroxyproline and deoxypyridinoline are observed following calcitonin treatment in both normal volunteers and patients with bone-related disorders, including Paget's disease and osteoporosis. The calcium-lowering effect of calcitonin is caused both by a decrease in the efflux of calcium from the bone to the ECF and inhibition of renal tubular reabsorption of calcium.
General characteristics of the active substance
Salmon calcitonin is rapidly absorbed and eliminated. Peak plasma concentrations are attained within the first hour of administration. Animal studies have shown that calcitonin is primarily metabolised via proteolysis in the kidney following parenteral administration. The metabolites lack the specific biological activity of calcitonin. Bioavailability following subcutaneous and intramuscular injection in humans is high and similar for the two routes of administration (71% and 66%, respectively). Calcitonin has short absorption and elimination half-lives of 10-15 minutes and 50-80 minutes, respectively. Salmon calcitonin is primarily and almost exclusively degraded in the kidneys, forming pharmacologically inactive fragments of the molecule. Therefore, the metabolic clearance is much lower in patients with end-stage renal failure than in healthy subjects. However, the clinical relevance of this finding is not known. Plasma protein binding is 30 to 40%.
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Characteristics in patients
There is a relationship between the subcutaneous dose of calcitonin and peak plasma concentrations. Following parenteral administration of 100 I.U. calcitonin, peak plasma concentration lies between about 200 and 400 pg/ml. Higher blood levels may be associated with increased incidence of nausea and vomiting.
Conventional long-term toxicity, reproduction, mutagenicity, and carcinogenicity studies have been performed in laboratory animals. Salmon calcitonin is devoid of embryotoxic, teratogenic and mutagenic potential. An increased incidence of pituitary adenomas has been reported in rats given synthetic salmon calcitonin for 1 year. This is considered a species-specific effect and of no clinical relevance. Salmon calcitonin does not cross the placental barrier. In lactating animals given calcitonin, suppression of milk production has been observed. Calcitonin is secreted into the milk.
Acetic acid, glacial, sodium acetate trihydrate, sodium chloride and water for injections.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
3 years. Forcaltonin should be used immediately after the single-use ampoule is opened.
Store in a refrigerator (2degC - 8degC) . Do not freeze.
Forcaltonin is contained in Type I, glass ampoules, designed to accommodate up to 1 ml of solution. Each pack contains 10 ampoules.
For subcutaneous, intramuscular or intravenous use. The product should be inspected visually for particulate matter and discoloration prior to administration. Any product where such defects are observed should be discarded. Any unused product or waste material should be disposed of in accordance with local requirements.
Medicinal product no longer authorised
Unigene UK Limited, 191 Sparrows Herne, Bushey Heath, Hertfordshire WD23 1AJ, UK
EU/1/98/093/002
Date of first authorization: 11-01-1999 Date of last renewal:
Medicinal product no longer authorised
Medicinal product no longer authorised