Introduction
Synthetic peptide, 32 residues long formulated as a nasal spray.
Uses
Salmon calcitonin is a synthetic peptide form of calcitonin used to inhibit bone resorption in the treatment of hypercalcemia, osteoporosis, and Paget's disease.
Used in the treatment of symptomatic Paget's disease for patients unresponsive to alternate treatments or intolerant to such treatments. In addition, it is used in emergency situations when serum calcium levels must be decreased quickly until the underlying condition is identified. It can also be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids and furosemide, oral phosphate or corticosteroids, or other agents. Calcitonin can be used in patients with azotemia and cases where intravenous fluids would be contraindicated due to limited cardiac reserves. Also for the treatment of post-menopausal osteoporosis in women more than 5 years post-menopause.
Associated Conditions
Pharmacodynamics
Calcitonin inhibits bone resorption by osteoclasts (bone remodeling cells) and promotes bone formation by osteoblasts. This leads to a net increase in bone mass and a reduction in plasma calcium levels. It also promotes the renal excretion of ions such as calcium, phosphate, sodium, magnesium, and potassium by decreasing tubular reabsorption. In consequence, there is an increase in the jejunal secretion of water, sodium, potassium, and chloride.
Mechanism of Action
Calcitonin binds to the calcitonin receptor (found primarily in osteoclasts) which then enhances the production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), leading to greater calcium retention and enhanced bone density. Binding of calcitonin to its receptor also activates adenylyl cyclase and the phosphatidyl-inositol-calcium pathway.
Absorption
Salmon calcitonin is rapidly absorbed with bioavailability of 71% following subcutaneous injection and 66% following intramuscular injection in humans. Via the nasal route, the bioavailability varies between 3 to 5% relative to IM.
Volume of Distribution
0.15 to 0.3 L/kg
Protein Binding
Protein binding is about 30 to 40%.
Route of Elimination
Urine. Studies with injectable calcitonin show increases in the excretion of filtered phosphate, calcium, and sodium by decreasing their tubular reabsorption in the kidney.
Half Life
Half-life elimination (terminal): I.M. 58 minutes; SubQ 59 to 64 minutes; Nasal: ~18 to 23 minutes
Toxicity
Salmon calcitonin was shown to inhibit lactation in animals and is not recommend in nursing mothers. While research in animals have shown a decrease in fetal weight, no studies have yet shown similar results in humans. It is recommended however to proceed carefully when administering salmon calcitonin to pregnant women and consider if the benefits outweigh the risks. Because of its protein nature, salmon calcitonin may provoke an allergy reaction (bronchospams and swelling of the tongue/throat) that can turn into a full-blown anaphylactic response. The manufacturer also reports an increase in the risk of malignancies from oral route (0.7%) to intranasal route (2.4%) compared to placebo. The same may apply to IV, IM and SC routes since the systemic exposure is higher in those cases. Nausea is noticeable in some patients but tends to decrease with continued administration. Rhinitis, headaches and back pain have also been reported among others.
Food Interactions
- Administer calcium supplement. Individuals who are taking salmon calcitonin for the treatment of postmenopausal osteoporosis should ingest at least 1000mg of elemental calcium daily (by food or through supplementation).
- Administer vitamin supplements. Individuals who are taking salmon calcitonin for the treatment of postmenopausal osteoporosis should take at least 400 international units of vitamin D daily.
Dosage
- Emergency treatment of hypercalcaemia: Up to 10 u/kg in 500 mL of sodium chloride 0.9% by slow IV infusion over at least 6 hr.
- Adjunct in hypercalcaemia: SC/IM: 4 u/kg 12 hrly, may increase after 1-2 days to 8 u/kg 12 hrly to max 8 u/kg 6 hrly after 2 days. Alternatively, 100 u every 6-8 hr, increased after 1-2 days to max 400 u every 6-8 hr.
- Paget's disease of bone: SC/IM: 50 u 3 times wkly to 100 u/day.
- Nasal postmenopausal osteoporosis: 200 u/day, alternation nostrils everyday.
