CALCITONIN

Posology Salmon calcitonin may be administered at bedtime to reduce the incidence of nausea or vomiting which may occur, especially at the initiation of therapy. 4), the treatment duration in all indications should be limited to the shortest period of time possible and using the minimum effective dose.

Prevention of acute bone loss due to sudden immobilisation such as in patients with recent osteoporotic fractures The recommended dosage is 100 IU daily or 50 IU twice daily administered subcutaneously or intramuscularly. The dose may be reduced to 50 IU daily at the start of remobilisation.

The recommended treatment duration is 2 weeks and should not exceed 4 weeks in any case due to the association of the increased risk of malignancies and long term calcitonin use. 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. Treatment should be discontinued once the patient has responded and symptoms have resolved. Duration of treatment should not normally exceed 3 months due to evidence of an increased risk of malignancies with long term calcitonin use.

g. in patients with impending pathologic fracture, treatment duration may be extended up to a recommended maximum of 6 months. 4). The effect of calcitonin may be monitored by measurement of suitable markers of bone remodelling, such as serum alkaline 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. 9% w/v sodium chloride solution may be administered over a period of at least 6 hours. As salmon calcitonin is a peptide, adsorption onto the plastic of the infusion set may occur.

This has the potential to reduce the total dose delivered to the patient. Frequent monitoring of the clinical and laboratory response including the measurement of serum calcium is recommended especially in the early phases of treatment.

The dosing of Calcitonin should be individualized to the patient’s specific requirements. Elderly population Experience with the use of calcitonin in the elderly has shown no evidence of reduced tolerability or altered dosage requirements.

Patients with hepatic impairment Experience with the use of calcitonin in patients with altered hepatic function has shown no evidence of reduced tolerability or altered dosage requirements. Patients with renal impairment The metabolic clearance is much lower in patients with end-stage renal failure than in healthy subjects.

2). Paediatric population There is insufficient evidence to support the use of salmon calcitonin in conditions associated with paediatric osteoporosis. Use of salmon calcitonin in children 0 to 18 years is therefore not recommended. Method of administration Intravenous, subcutaneous, or intramuscular use.

The most frequently observed undesirable effects are nausea, vomiting and flushing. They are dose dependent and more frequent after intravenous than after intramuscular or subcutaneous 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).

Neoplasms benign, malignant and unspecified (incl cysts and polyps) Common:

Malignancy (with long term use).

Immune system disorders Uncommon:

Hypersensitivity.

Very rare:

Serious allergic-type reactions such as bronchospasm, swelling of the tongue and throat, anaphylactic shock. 3 Not known: Hypocalcemia.

Nervous system disorders Common:

Dizziness, headache, dysgeusia.

Not known:

Tremor.

Eye disorders Uncommon:

Visual disturbance. 4 Uncommon: Hypertension. 2 Common: Diarrhoea, abdominal pain.

Skin and subcutaneous tissue disorders Uncommon:

Rash generalised, pruritus.

Not known:

Urticaria.

Musculoskeletal and connective tissue disorders Common:

Musculoskeletal pain including arthralgia.

Renal and urinary disorders Uncommon:

Polyuria.

General disorders and administration site conditions Common:

Fatigue.

Uncommon:

Influenza-like symptoms, oedema (facial, peripheral and generalised), injection site reaction. 1 The frequencies of the above listed undesirable effects are partly based on results from clinical trials with calcitonin 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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. 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.

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.

16% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1. Calcitonin is also contraindicated in patients with hypocalcaemia.