Calcitonin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Miacalcin: 200 units/mL (2 mL) [contains phenol]

Solution, Nasal:

Fortical: 200 units/actuation (3.7 mL [DSC])

Miacalcin: 200 units/actuation (3.7 mL [DSC])

Generic: 200 units/actuation (3.7 mL)

Pharmacology

Mechanism of Action

Peptide sequence similar to human calcitonin; functionally antagonizes the effects of parathyroid hormone. Directly inhibits osteoclastic bone resorption; promotes the renal excretion of calcium, phosphate, sodium, magnesium, and potassium by decreasing tubular reabsorption; increases the jejunal secretion of water, sodium, potassium, and chloride

Pharmacokinetics/Pharmacodynamics

Absorption

Intranasal: Rapidly but highly variable and lower than IM administration

Distribution

V_d: 0.15 to 0.3 L/kg

Metabolism

Metabolized in kidneys, blood and peripheral tissue

Excretion

Urine (as inactive metabolites); Clearance: Salmon calcitonin: 3.1 mL/kg/minute

Onset of Action

Hypercalcemia: IM, SubQ: ~2 hours

Paget's disease: Within a few months; may take up to 1 year for neurologic symptom improvement

Time to Peak

Plasma: SubQ ~23 minutes; Nasal: ~10 to 13 minutes

Duration of Action

Hypercalcemia: IM, SubQ: 6 to 8 hours; following multiple doses, hypercalcemic effect diminishes within 24 to 48 hours (Nilsson 1978; Stevenson 1988)

Half-Life Elimination

Terminal: IM 58 minutes; SubQ 59 to 64 minutes; Nasal: ~18 to 23 minutes

Use: Labeled Indications

Hypercalcemia (injection): Adjunctive therapy for hypercalcemia. May be used in hypercalcemic emergencies when a rapid decrease in serum calcium is required or until more specific treatment of underlying disease is accomplished.

Osteoporosis (intranasal or injection): Treatment of osteoporosis in females more than 5 years postmenopause.

Paget disease (injection): Treatment of symptomatic Paget disease of bone (osteitis deformans) in patients who are nonresponsive or intolerant to alternative therapy.

Contraindications

Hypersensitivity to calcitonin salmon or any component of the formulation

Dosage and Administration

Dosing: Adult

Note: Patients treated for osteoporosis or Paget disease should receive supplemental calcium and vitamin D if dietary intake is inadequate.

Hypercalcemia: Initial: IM, SubQ: 4 units/kg every 12 hours; if response is unsatisfactory after 24 to 48 hours, may increase to 8 units/kg every 12 hours; if response remains unsatisfactory after an additional 48 hours, may increase to a maximum dose of 8 units/kg every 6 hours. Hypocalcemic effect of calcitonin diminishes after 24 to 48 hours (Bilezikian 1993; Nilsson 1978; Stevenson 1988).

Osteoporosis, treatment (postmenopausal females) (alternative agent): Note: Due to limited comparative efficacy with other therapies, as well as concerns related to increased malignancy with long-term use, calcitonin is rarely used and should only be considered if no other therapies are appropriate (AACE/ACE [Camacho 2016]; ES [Eastell 2019]). Short-term treatment may provide analgesic effect in patients with acute painful vertebral fractures (AACE/ACE [Camacho 2016]).

IM, SubQ: 100 units daily.

Intranasal: 200 units (1 spray) in one nostril once daily.

Paget disease (alternative agent): IM, SubQ: 100 units daily. Lower maintenance dosages (eg, 50 units 3 times/week) may be sufficient (DeRose 1974).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Osteogenesis imperfecta: Infants >6 months, Children, and Adolescents: IM, SubQ: 2 units/kg/dose 3 times/week (Castells, 1979)

Reconstitution

Injection: NS has been recommended for the dilution to prepare a skin test in patients with suspected sensitivity.

Administration

Injection: May be administered IM or SubQ. IM route is preferred if the injection volume is >2 mL (use multiple injection sites if dose volume is >2 mL). SubQ route is preferred for outpatient self-administration unless the injection volume is >2 mL.

Nasal spray: Before first use, allow bottle to reach room temperature, then prime pump by releasing until a full spray is produced. To administer, place nozzle into nostril with head in upright position. Alternate nostrils daily. Do not prime pump before each daily use. Discard after 30 doses.

Dietary Considerations

Patients with Paget's disease and hypercalcemia should follow a low calcium diet as prescribed. Recommended amounts of vitamin D and calcium intake is essential for preventing/treating osteoporosis. If dietary intake is inadequate, dietary supplementation is recommended. Females and males should consume:

Calcium: 1,000 mg/day (males: 50 to 70 years) or 1,200 mg/day (females ≥51 years and males ≥71 years) (IOM 2011; NOF [Cosman 2014]).

Vitamin D: 800 to 1,000 units/day (males and females ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 units/day (males and females ≤70 years) or 800 units/day (males and females ≥71 years) (IOM 2011).

Storage

Injection: Store under refrigeration at 2°C to 8°C (36°F to 46°F); protect from freezing. The following stability information has also been reported: May be stored at room temperature for up to 14 days (Cohen, 2007).

Nasal: Store unopened bottle under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze.

Fortical: After opening, store for up to 30 days at 20˚C to 25˚C (68˚F to 77˚F); excursions permitted to 15°C to 30°C (59°F to 86°F). Store in upright position.

Miacalcin: After opening, store for up to 35 days at room temperature of 15°C to 30°C (59°F to 86°F). Store in upright position.

Drug Interactions

Lithium: Calcitonin may decrease the serum concentration of Lithium. Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Zoledronic Acid: Calcitonin may enhance the hypocalcemic effect of Zoledronic Acid. Monitor therapy

Adverse Reactions

Unless otherwise noted, frequencies reported are with nasal spray.

>10%: Respiratory: Rhinitis (<12%, including ulcerative)

1% to 10%:

Cardiovascular: Flushing (injection: 2% to 5%, hands or face; nasal spray: <1%)

Central nervous system: Depression (1% to 3%), dizziness (1% to 3%), paresthesia (1% to 3%)

Dermatologic: Erythematous rash (1% to 3%)

Gastrointestinal: Nausea (injection: 10%; nasal spray: 1% to 3%), abdominal pain (1% to 3%)

Hematologic & oncologic: Malignant neoplasm (5%), lymphadenopathy (1% to 3%)

Infection: Infection (1% to 3%)

Local: Injection site reaction (injection: 10%)

Neuromuscular & skeletal: Back pain (5%), myalgia (1% to 3%), osteoarthritis (1% to 3%)

Ophthalmic: Abnormal lacrimation (1% to 3%), conjunctivitis (1% to 3%)

Respiratory: Bronchospasm (1% to 3%), flu-like symptoms (1% to 3%), sinusitis (1% to 3%), upper respiratory tract infection (1% to 3%)

<1%, postmarketing, and/or case reports (all routes): Alopecia, altered sense of smell, anaphylactic shock, anaphylactoid reaction, anaphylaxis, anorexia, antibody development (drug efficacy can be affected), arthralgia, casts in urine, cough, decreased appetite (injection), diaphoresis, diarrhea, dysgeusia, dyspnea, earlobe pruritus (injection), edema, excoriation (nasal mucosa), eye pain, facial edema, fever, headache, hearing loss, hypersensitivity reaction, hypertension, hypocalcemia, musculoskeletal pain, nasal mucosa ulcer, nocturia, pedal edema, peripheral edema, polyuria, pruritus, salty taste (injection), skin rash, sneezing, tachycardia, tinnitus, tremor, urine abnormality, urticaria (injection), visual disturbance, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Salmon-derived products: Anaphylactic shock, anaphylaxis, bronchospasm, and swelling of the tongue or throat have been reported; have epinephrine immediately available for a possible hypersensitivity reaction. A skin test should be performed prior to initiating therapy of calcitonin salmon in patients with suspected sensitivity; a detailed skin testing protocol is available from the manufacturer.
• Hypocalcemia: Hypocalcemia with tetany and seizure activity has been reported. Hypocalcemia and other disorders affecting mineral metabolism (eg, vitamin D deficiency) should be corrected before initiating therapy; monitor serum calcium and symptoms of hypocalcemia during therapy. Administer in conjunction with calcium and vitamin D when treating Paget disease or postmenopausal osteoporosis.
• Malignancy: Analyses of randomized controlled trials (in osteoporosis and osteoarthritis) using the nasal spray and oral formulations have demonstrated a statistically significant increase in the risk of the development of cancer in calcitonin-treated patients (compared to placebo). The risk for malignancies is associated with long-term use of calcitonin (trials ranged from 6 months to 5 years in duration). Periodically reassess continued use of calcitonin therapy, carefully considering the risks versus benefits. Similar risk for other routes (subcutaneous, IM, IV) cannot be ruled out.
• Urinary sediment abnormalities: Coarse granular casts and casts containing renal tubular epithelial cells were observed following use in young adults on bed rest during a study to examine the effect of immobilization on osteoporosis; no other renal abnormalities were reported and sediment normalized after discontinuation; consider monitoring urine sediment periodically; however, the clinical significance of this finding is unknown.

Disease-related concerns:

• Osteoporosis: Risk vs benefit: Fracture reduction efficacy has not been demonstrated; use has not been shown to increase spinal bone mineral density in early postmenopausal females. Use should be reserved for postmenopausal females for whom alternative treatments are not suitable (eg, patients for whom other therapies are contraindicated or for patients who are intolerant or unwilling to use other therapies). Consider potential benefits of therapy against risks, including the potential risk for malignancy with long-term use. Short-term treatment may provide analgesic effect in patients with acute painful vertebral fractures (AACE/ACE [Camacho 2016]).

Dosage form specific issues:

• Nasal spray: Rhinitis and epistaxis have been reported; mucosal alterations may occur. Perform nasal examinations with visualization of the nasal mucosa, turbinates, septum and mucosal blood vessels prior to initiation of therapy, periodically during therapy, and at any time nasal symptoms occur. Temporarily withdraw use if ulceration of nasal mucosa occurs. Discontinue for severe ulcerations >1.5 mm, those that penetrate below the mucosa, or those associated with heavy bleeding. Patients >65 years of age may experience a higher incidence of nasal adverse events with calcitonin nasal spray.

Other warnings/precautions:

• Antibody formation: Antibody formation to calcitonin-salmon has been reported with the injection and nasal spray. Consider the possibility of antibody formation in patients who initially respond to therapy but later do not respond to treatment.

Monitoring Parameters

Osteoporosis: Serial bone mineral density (BMD) should be evaluated at baseline and every 1 to 3 years (usually at ~2 years following initiation of therapy, then more or less frequently depending on patient-specific factors and stability of BMD) (AACE/ACE [Camacho 2016]; ES [Eastell 2019]; NOF [Cosman 2014]); serum calcium and 25(OH)D; may consider monitoring biochemical markers of bone turnover (eg, fasting serum CTX or urinary NTX) at baseline, 3 months, and 6 months, to assess treatment response and/or adherence to therapy (ES [Eastell 2019]).

Paget disease: Serum total alkaline phosphatase at 6 to 12 weeks for initial response to treatment (when bone turnover will have shown a substantial decline) and potentially at 6 months (maximal suppression of high bone turnover) and then at ~6 to 12-month intervals (Endocrine Society [Singer 2014]); monitoring more specific biochemical markers of bone turnover (eg, serum P1NP, NTX, serum beta-CTx) is generally only warranted in patients with Paget disease who have abnormal liver or biliary tract function or when early assessment of response to treatment is needed (eg, spinal compression, very active disease) (Endocrine Society [Singer 2014]); serum calcium and 25(OH)D; pain (posttreatment pain may not strictly correlate with increased biochemical markers [Ralston 2019]).

Nasal formulation: Visualization of nasal mucosa, turbinate, septum, and mucosal blood vessels (at baseline and with nasal complaints).

Consider periodic examinations of urine sediment.

Pregnancy

Pregnancy Considerations

Endogenous calcitonin does not cross the placenta (Dochez 2015). Information related to the use of calcitonin in pregnancy is limited (Koren 2018; Krysiak 2011; Richa 2018; Turek 2012).

Patient Education

What is this drug used for?

• It is used to treat Paget disease.
• It is used to treat high calcium levels.
• It is used to treat soft, brittle bones (osteoporosis) in women after change of life.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Runny nose
• Headache
• Back pain
• Muscle pain
• Flushing
• Nausea
• Vomiting

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low calcium like muscle cramps or spasms, numbness and tingling, or seizures.
• Severe stuffy nose
• Nasal sores
• Nosebleed
• Severe injection site irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.