Pronunciation

(kal si TOE nin)

Index Terms

• Calcitonin (Salmon)
• Salcatonin

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)

Brand Names: U.S.

• Fortical [DSC]
• Miacalcin

Pharmacologic Category

• Antidote
• Hormone

Pharmacology

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

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

Injection:

Hypercalcemia: Adjunctive therapy for hypercalcemia

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

Postmenopausal osteoporosis: Treatment of osteoporosis in women more than 5 years postmenopause

Intranasal:

Postmenopausal osteoporosis: Treatment of postmenopausal osteoporosis in women more than 5 years postmenopause

Contraindications

Hypersensitivity to calcitonin salmon or any component of the formulation

Dosing: Adult

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

Hypercalcemia: Initial: IM, SubQ: 4 units/kg every 12 hours; may increase up to 8 units/kg every 6 to 12 hours; hypocalcemic effect of calcitonin diminishes after 24 to 48 hours (Bilezikian 1993; Nilsson 1978; Stevenson 1988)

Postmenopausal osteoporosis:

IM, SubQ: 100 units daily

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

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. Women and men should consume:

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

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

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.

• 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: Definitive efficacy of calcitonin-salmon in decreasing fractures is lacking compared to other agents approved for osteoporosis treatment. Consider potential benefits of therapy against risks, including the potential risk for malignancy with long-term use.

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:

• Appropriate use: Fracture reduction efficacy has not been demonstrated; use has not been shown to increase spinal bone mineral density in early postmenopausal women. Use should be reserved for patients 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).

Monitoring Parameters

Osteoporosis: Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 2 years thereafter (NOF [Cosman, 2014]); annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; consider measuring biochemical markers of bone turnover

Paget disease: Alkaline phosphatase; pain; serum calcium and 25(OH)D

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 Risk Factor

C

Pregnancy Considerations

Miacalcin is not indicated for use in women of reproductive potential. Adverse events have been observed in animal reproduction studies. Calcitonin does not cross the placenta.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinorrhea, headache, back pain, muscle pain, flushing, nausea, or vomiting. Have patient report immediately to prescriber signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures), severe rhinitis, nasal sores, nosebleed, or severe injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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