CALCITONIN Solution for injection / infusion Ref.[49935] Active ingredients: Calcitonin

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 section 4.8). Skin testing should be conducted in patients with suspected sensitivity to calcitonin prior to their treatment with calcitonin.

Analyses of randomised controlled trials conducted in patients with osteoarthritis and osteoporosis have shown that calcitonin is associated with a statistically significant increase in the risk of cancer compared to patients treated with placebo. These trials demonstrated an increase in the absolute risk of cancer occurrence for patients treated with calcitonin compared to placebo which varied between 0.7% and 2.4% with long term therapy. Patients in these trials were treated with oral or intra-nasal formulations however it is likely that an increased risk also applies when calcitonin is administered subcutaneously, intramuscularly or intravenously especially for long-term use, as systemic exposure to calcitonin in such patients is expected to be higher than for other formulations.

Calcitonin 50 IU/ml contains less than 23 mg sodium per 1ml, and can be considered as ‘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.

Concomitant use of calcitonin and lithium may lead to a reduction in plasma lithium concentrations. The dose of lithium may need to be adjusted.

Pregnancy

Calcitonin has not been studied in pregnant women. Calcitonin should be used during pregnancy only if treatment is considered absolutely essential by the physician.

Breast-feeding

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 section 5.3). Therefore, breast-feeding is not recommended during treatment.

Fertility

There are no data regarding a potential influence of Calcitonin on human fertility.

No studies exist on the effects of Calcitonin on the ability to drive and use machines. Calcitonin may cause fatigue, dizziness and visual disturbances (see section 4.8) which may impair the patient’s reaction. Patients must therefore be warned that these effects may occur, in which case they should not drive or use machines.

The most frequently observed undesirable effects are nausea, vomiting and flushing. They are dose dependent and more frequent after i.v. than after i.m. or s.c. administration.

Adverse drug reactions from multiple sources including clinical trials and post-marketing experience are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.

Adverse reactions have been ranked under headings of frequency using the following convention: 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), not known (cannot be estimated from the available data).

The frequencies of the above listed undesirable effects are partly based on results from clinical trials with nasal spray.

¹ Development of neutralising antibodies to calcitonin. 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.

² 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.

³ In case of patients with high bone remodelling (Paget’s disease and young patients) a transient decrease of calcemia may occur between the 4th and the 6th hour after administration, usually asymptomatic.

⁴ Flushing (facial or upper body) is not an allergic reaction but is due to a pharmacological effect, and is usually observed 10 to 20 minutes after administration.

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 at: www.mhra.gov.uk/yellowcard.

Glass or hard plastic i.v. containers should not be used.