Salmon Calcitonin

Approved Indications:

• Postmenopausal Osteoporosis
  Indicated for the treatment of osteoporosis in postmenopausal women more than 5 years post-menopause, particularly those at high risk of fractures and who cannot tolerate other agents.
• Paget’s Disease of Bone
  For the treatment of moderate to severe Paget’s disease of bone in patients who do not respond to or cannot tolerate alternative therapies.
• Hypercalcemia of Malignancy
  Used in emergency treatment to reduce elevated serum calcium levels associated with cancer.

Off-label/Clinically Accepted Uses:

• Osteogenesis Imperfecta
  Used occasionally to manage bone pain and reduce fracture frequency in children and adults.
• Bone Pain in Metastatic Disease or Fractures
  Utilized for refractory bone pain, particularly related to vertebral compression fractures.

Postmenopausal Osteoporosis

• Intranasal: 200 IU once daily, administered in alternating nostrils.
• Injectable (SC or IM): 100 IU daily; less commonly used for this indication.

Paget’s Disease

• Injection (SC or IM): 100 IU once daily.
• May reduce frequency to every other day after improvement.

Hypercalcemia of Malignancy

• Injection (SC or IM): Start at 4 IU/kg every 12 hours.
• Dose may be increased to 8 IU/kg every 6 hours if no response.

Special Populations:

• Renal/Hepatic Impairment: No dose adjustment required, but monitor calcium closely.
• Elderly: No adjustment required.
• Pediatric Use: Off-label use only; not generally recommended except under specialist supervision.

Administration Guidelines:

• Rotate injection sites to prevent irritation.
• Nasal spray should be at room temperature before use.
• Avoid using the same nostril daily to prevent mucosal damage.

Salmon calcitonin is a synthetic analog of the natural hormone calcitonin, derived from salmon, which has a higher potency and longer half-life than human calcitonin. It binds to specific calcitonin receptors on osteoclasts, inhibiting their activity and thereby reducing bone resorption. This leads to a decrease in the release of calcium from bones into the blood. In the kidneys, it reduces tubular reabsorption of calcium and phosphate, enhancing their urinary excretion. These combined effects result in a reduction in serum calcium levels and stabilization of bone metabolism.

• Absorption:
• Intranasal bioavailability: ~3%
• Subcutaneous/Intramuscular: Rapid, with peak levels in 1 hour
• Distribution:
• Moderately bound to plasma proteins
• Distributed widely in extracellular fluid
• Metabolism:
• Rapidly metabolized in blood, kidney, and liver into inactive fragments
• Excretion:
• Primarily excreted via urine
• Terminal half-life: 1 hour (parenteral)
• Onset of Action:
• Injection: 1–2 hours
• Nasal spray: Slightly delayed due to lower absorption

• Pregnancy: Category C (FDA – historical classification)
  Animal studies have shown adverse effects on fetal development. No adequate human studies are available. Use only if the potential benefit justifies the potential risk to the fetus.
• Lactation:
  Unknown whether salmon calcitonin is excreted into human milk. Due to the potential for suppression of calcium metabolism in the infant, use caution or avoid use during breastfeeding.

• Primary Class: Hormonal Calcium Regulator
• Subclass: Synthetic Calcitonin (Salmon-derived)

• Known hypersensitivity to salmon calcitonin or any of its formulation components
• Hypocalcemia
• History of serious allergic or anaphylactic reaction to calcitonin
• Structural abnormalities of the nasal cavity (for nasal spray formulation)

• Hypocalcemia: Monitor calcium and vitamin D levels; supplement as necessary.
• Hypersensitivity Reactions: Severe allergic reactions including anaphylaxis have occurred. Consider skin testing before first use in high-risk patients.
• Nasal Adverse Effects: Nasal irritation, dryness, and epistaxis are common with intranasal use; inspect nasal mucosa regularly.
• Malignancy Risk: Long-term use has been associated with a small increased risk of cancer in some studies; use lowest effective dose for the shortest duration.
• Monitoring: Periodically assess serum calcium and nasal mucosa (for nasal formulation).

Common Adverse Effects

• Intranasal:
• Nasal dryness or irritation
• Rhinitis
• Epistaxis
• Back pain
• Arthralgia
• Headache
• Injection:
• Nausea
• Flushing of face or hands
• Injection site reactions
• Abdominal pain

Serious or Rare Adverse Effects

• Hypocalcemia (symptomatic)
• Anaphylaxis or serious hypersensitivity
• Bronchospasm (rare)
• Increased risk of malignancies with long-term use (nasal formulation)
• Visual disturbances

Timing: Side effects usually occur early during therapy and may diminish with continued use.

• Calcium Supplements or Vitamin D: May alter the drug’s hypocalcemic effect; monitor levels.
• Lithium: May reduce serum lithium concentrations due to increased renal clearance.
• Bisphosphonates: May cause additive effects on calcium lowering; concurrent use is usually not recommended.
• Aminoglycosides: Risk of enhanced hypocalcemia when combined.
• Enzyme Pathways: Not metabolized by CYP450 enzymes; minimal risk of metabolic drug interactions.

• Regulatory Warnings: Both EMA and FDA issued warnings related to a small increased risk of malignancies with prolonged use of nasal calcitonin.
• Guideline Revisions: Major guidelines now recommend limiting use to patients intolerant of bisphosphonates or other first-line agents.
• Therapeutic Role: Due to lower anti-fracture efficacy and safety concerns, salmon calcitonin is no longer considered a first-line therapy for osteoporosis.

• Nasal Spray:
• Store unopened bottles at 2°C to 8°C (refrigerator).
• After opening, store at room temperature (20°C to 25°C) for up to 35 days.
• Do not freeze. Keep upright and tightly capped.
• Injection (SC/IM):
• Store in a refrigerator at 2°C to 8°C.
• Do not freeze.
• Once opened, use multi-dose vials within 14 days.