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Calcitonin

Pronunciation

Class: Parathyroid
VA Class: HS900
CAS Number: 47931-85-1
Brands: Fortical, Miacalcin

Introduction

Polypeptide hormone secreted by parafollicular cells (C cells) of thyroid gland; acts predominantly on bone to lower serum calcium concentration and inhibit bone resorption.125

Uses for Calcitonin

Paget’s Disease of Bone

Treatment of Paget’s disease of bone.125 Consider treatment with calcitonin or a bisphosphonate (e.g., alendronate, etidronate, pamidronate, risedronate) in patients with biochemical markers suggestive of an increase in bone remodeling, those who are symptomatic, and those at risk for future complications from their disease (e.g., those with pagetic lesions in weight-bearing regions or adjacent to joints).143

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Hypercalcemia

Early treatment of hypercalcemic emergencies (with other appropriate agents) when a rapid decrease in serum calcium concentration is required.125

Postmenopausal Osteoporosis

Treatment of postmenopausal osteoporosis in women >5 years postmenopause; use supplemental calcium and/or vitamin D concomitantly if daily dietary intake is considered inadequate.125 127 145

Corticosteroid-induced Osteoporosis

Has been used in the treatment of corticosteroid-induced osteoporosis in patients receiving long-term corticosteroid therapy.126 Considered second-line therapy for patients with low bone mineral density (BMD) during corticosteroid therapy, particularly when bisphosphonate (e.g., alendronate, risedronate) is contraindicated or not tolerated or when such patients refuse bisphosphonate therapy.126

Not recommended for prevention of bone loss in patients just beginning corticosteroid therapy; efficacy not established for this indication.126

Calcitonin Dosage and Administration

General

Paget’s Disease of Bone

  • Monitor by periodic determinations of serum alkaline phosphatase and urinary hydroxyproline excretion as well as evaluation of symptoms.125

  • Investigate possibility of antibody formation in any patient who shows initial response but subsequently relapses.125

Postmenopausal Osteoporosis

Administration

Administer by sub-Q or IM injection (Paget’s disease of bone, hypercalcemia, postmenopausal osteoporosis)125 or intranasally (postmenopausal osteoporosis).127 145

IM Administration

IM injection preferred when injection volume >2 mL.125

Use multiple sites of injection when volume >2 mL.125

Sub-Q Administration

Sub-Q injection preferred for patient self-administration.125

Intranasal Administration

Administer once daily (as a single spray in 1 nostril) using metered-dose spray pump supplied by manufacturer.127 145 Alternate nostrils daily.127 145

Allow solution to reach room temperature before priming pump and administering first dose.127 145

Prime pump before first dose; do not prime before each dose.127 145

Miacalcin: To prime pump, hold bottle upright and depress the 2 white side arms of pump toward the bottle until full spray is produced.127

Fortical: To prime pump, hold bottle upright and depress the 2 white side arms of pump toward the bottle at least 5 times until full spray is produced.145

Administer dose by placing nozzle in nostril with head in upright position and firmly depressing pump toward bottle.127 145

Discard spray pump after 30 actuations, since the correct drug dose per actuation cannot be assured if used for additional doses.127

Dosage

Activity of calcitonin salmon expressed in terms of International Units (units).125 127 145

Intranasal spray pumps deliver 0.09 mL of solution per actuation; each 0.09-mL spray delivers 200-unit dose.127 145

Adults

Paget’s Disease of Bone
Sub-Q or IM

Initial dosage: 100 units (0.5 mL) daily.125

Maintenance: 50 units (0.25 mL) daily or every other day; higher dosage (100 units daily) appropriate in patients with serious deformity or neurologic involvement.125

Dosage >100 units daily usually does not produce an improved response in patients who relapse while receiving calcitonin.101 105 109 110 111 112 125

Hypercalcemia
Sub-Q or IM

Initially, 4 units/kg every 12 hours; may increase dosage after 1 or 2 days (if response not adequate) to 8 units/kg every 12 hours; may further increase dosage after 2 days (if response not adequate) to 8 units/kg every 6 hours.125

Postmenopausal Osteoporosis
Sub-Q or IM

Minimum effective dosage not established; 100 units every other day may be effective in preserving vertebral BMD.125

Intranasal

200 units (1 spray) daily.127 145

Prescribing Limits

Adults

Hypercalcemia
Sub-Q or IM

Maximum 8 units/kg every 6 hours.125

Cautions for Calcitonin

Contraindications

  • Known hypersensitivity to calcitonin salmon.125 127 145

Warnings/Precautions

Sensitivity Reactions

Serious allergic reactions (bronchospasm, swelling of tongue or throat, anaphylactic shock, at least 1 death due to anaphylaxis) reported in patients receiving calcitonin injection.125 127 145 Differentiate hypersensitivity reactions from generalized flushing and hypotension.125

Allergic-type reactions also reported in patients receiving calcitonin nasal spray.127 145

Appropriate agents for treatment of hypersensitivity reactions should be readily available.125 127 145

For patients with suspected sensitivity to calcitonin, consider skin testing prior to initiating therapy.125 127 145

General Precautions

Hypocalcemic Tetany

Possibility of hypocalcemic tetany following parenteral administration;8 111 125 have calcium injection readily available, particularly during first several doses of parenteral calcitonin.125

Laboratory Monitoring

Coarse granular casts and casts containing renal tubular epithelial cells reported in some young adult volunteers at bedrest who received parenteral calcitonin in a study of its effect on immobilization osteoporosis.34 125 Clcr not altered and proteinuria not reported; urine sediment returned to normal within 4 days following drug discontinuance.34 125 Effect not reported by other investigators.125 127

Periodic examinations of urine sediment are recommended in patients receiving long-term parenteral therapy.34 125 145

Radiographic Monitoring

In patients with Paget’s disease, carefully evaluate radiographic evidence of marked progression of pagetic lesions to rule out osteogenic sarcoma (since frequency is increased in patients with Paget’s disease).125

Nasal Examinations

Periodic nasal examinations with visualization of nasal mucosa, turbinates, septum, and mucosal blood vessel status are recommended for patients receiving calcitonin nasal spray.127 145

Discontinue nasal spray if severe ulceration of nasal mucosa (i.e., ulcers >1.5 mm in diameter or penetrating below the mucosa, ulcers associated with heavy bleeding) occurs.127 145 For smaller ulcers, interrupt therapy until healing occurs.127 145

Specific Populations

Pregnancy

Category C.125 127 145

Lactation

Inhibits lactation in animals.125 127 145 Not known whether calcitonin is distributed into human milk.125 127 145 Use not recommended.125 127 145

Pediatric Use

Experience with calcitonin in children with juvenile Paget’s disease is very limited; the relationship between this disorder and adult Paget’s disease is not established.125

Experience with calcitonin in children with idiopathic juvenile osteoporosis is very limited; the relationship between this disorder and postmenopausal osteoporosis is not established.127 145

Data are inadequate to support use of calcitonin in children.125 127 145

Geriatric Use

Adverse nasal effects (i.e., rhinitis, irritation, congestion) reported more frequently in patients >65 years of age receiving calcitonin nasal spray.127 145 Nasal effects described as mild.127 145

Common Adverse Effects

With parenteral therapy, nausea,125 118 vomiting,118 125 injection site reaction,125 flushing of the face, ears, hands, and feet.24 100 102 104 106 107 117 118 120 125

With intranasal therapy, rhinitis, nasal symptoms, back pain.127 145

Interactions for Calcitonin

Bisphosphonates

Possible reduced antiresorptive response to calcitonin in patients with Paget’s disease previously treated with bisphosphonates.127 145

Calcitonin Pharmacokinetics

Absorption

Bioavailability

Destroyed in GI tract; administer parenterally or intranasally.125 127 145

Rapidly absorbed by nasal mucosa; bioavailability of intranasal dose relative to IM dose is approximately 3%.127 145

Onset

With IM or sub-Q administration, 15 minutes.c

Reduction in serum calcium concentration in patients with hypercalcemia evident within about 2 hours after first injection.125

Clinical and/or biochemical effects in Paget’s disease may not be evident for several months.125

Duration

With IM or sub-Q administration, 8–24 hours.c

Reduction in serum calcium concentration in patients with hypercalcemia persists for about 6–8 hours after single injection.125

Distribution

Extent

Not studied extensively.125 127 145

Apparently does not cross placenta.125 127 145

Elimination

Metabolism

Appears to be rapidly metabolized to smaller inactive fragments in kidney, blood, and peripheral tissues.125

Elimination Route

Excreted in urine as metabolites.125

Half-life

<1 hour.114 127

Stability

Storage

Parenteral

Injection

2–8°C.125

Intranasal

Nasal Solution

Miacalcin and Fortical new unassembled bottles: 2–8°C; protect from freezing.127 145

Miacalcinbottle in use: 15–30°C, in upright position for up to 35 days.127

Fortical bottle in use: 20–25°C, in upright position for up to 30 days.145

Actions and Spectrum

  • Commercially available as calcitonin salmon.125 127 145 Prepared synthetically or using recombinant DNA technology; contains the 32 amino acids in the same linear sequence as occurs in natural calcitonin of salmon origin.125 127 145 Calcitonin salmon prepared by recombinant DNA technology is structurally identical to calcitonin salmon produced by chemical synthesis.145

  • Calcitonin salmon has same pharmacologic activity as calcitonin human, but calcitonin salmon is more potent and has longer duration of action.100 101 102 103 104 109 112 114 125 127 145

  • Acts predominantly on bone to lower serum calcium concentration;125 127 145 also has direct effects on kidneys and GI tract.125

  • Directly inhibits osteoclastic bone resorption, altering the function and/or number of osteoclasts.125 127 145

  • In most patients with Paget’s disease, causes a decrease in the rate of bone turnover with a resultant decrease in elevated serum alkaline phosphatase concentrations and urinary hydroxyproline excretion.125 These changes appear to correspond to changes toward more normal bone formation.125

Advice to Patients

  • If patient or caregiver is to administer parenteral calcitonin, provide careful instructions on proper administration methods, including aseptic technique.125

  • For patients using calcitonin nasal spray, provide careful instruction on storage, pump assembly, priming of pump, and administration.127 145 Advise patients to record number of doses used and to discard the bottle after 30 doses.127

  • Advise patients using calcitonin nasal spray to notify their clinician if nasal irritation develops.127 145

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.125 127 145

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.125 127 145

  • Importance of informing patients of other important precautionary information.125 127 145 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcitonin (Salmon)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Nasal

Solution

200 units/metered spray

Miacalcin (synthetic)

Novartis

Fortical (recombinant DNA origin)

Upsher-Smith

Parenteral

Injection

200 units/mL*

Miacalcin (synthetic; with phenol 5 mg/mL)

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Calcitonin (Salmon) 200UNIT/ACT Solution (PAR): 4/$112.97 or 11/$308.07

Calcitonin (Salmon) 200UNIT/ACT Solution (SANDOZ): 4/$109.99 or 11/$299.97

Miacalcin 200UNIT/ACT Solution (NOVARTIS): 4/$145.99 or 7/$279.96

Miacalcin 200UNIT/ML Solution (NOVARTIS): 2/$70.99 or 6/$194.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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20. Crosbie WA, Woodhouse NJY. Effect of salmon calcitonin treatment on bone turnover, cardiac output and oxygen transport in patients with Paget’s disease. Clin Sci Mol Med. 1974; 48:5-6P.

21. Hamilton CR Jr. Effects of synthetic salmon calcitonin in patients with Paget’s disease of bone. Am J Med. 1974; 56:315-22. [IDIS 46922] [PubMed 4855941]

22. DeRose J, Singer FR, Avramides A et al. Response of Paget’s disease to porcine and salmon calcitonins—effects on long-term treatment. Am J Med. 1974; 56:858-66. [IDIS 44624] [PubMed 4857531]

24. Kanis JA, Horn DB, Scott RDM et al. Treatment of Paget’s disease of bone with synthetic salmon calcitonin. Br Med J. 1974; 3:727-31. [IDIS 49113] [PubMed 4472416]

33. Singer FR, Aldred JP, Neer RM et al. An evaluation of antibodies and clinical resistance to salmon calcitonin. J Clin Invest. 1972; 51:2331-8. [IDIS 28595] [PubMed 4674133]

34. Hantman DA, Donaldson CL, Hulley SB. Abnormal urinary sediment during therapy with synthetic salmon calcitonin. J Clin Endocrinol Metab. 1971; 33:564-6. [IDIS 21062] [PubMed 5106277]

98. Ciba Pharmaceutical Company. Cibacalcin (calcitonin human for injection) prescribing information. Summit, NJ; 1988 Feb.

99. Rorer. Calcimar (calcitonin salmon injection) prescribing information. Fort Washington, PA; 1989 Jun.

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c. AHFS drug information 2003. McEvoy GK, ed. Calcitonin. Bethesda, MD: American Society of Health-System Pharmacists; 2003: page 3039-42.

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