Calcitonin is a polypeptide hormone produced in the parafollicular (C) cells of the thyroid gland in humans; the hormone binds directly to receptors on the osteoclast surface, inhibiting bone resorption and decreases serum calcium. Commercial preparations of salmon calcitonin are prepared synthetically or using recombinant DNA methods. Salmon calcitonin is 40 to 50 times more potent and has a longer duration than human calcitonin; its structure differs from human calcitonin by 13 amino acid residues. Calcitonin has been used in the treatment of Paget's disease of the bone, either alone or with other agents for the management of hypercalcemia, and for postmenopausal osteoporosis. Injectable calcitonin is used clinically in treatment protocols hypercalcemic emergencies to help produce a rapid decrease in serum calcium until more specific treatment of the underlying disease is instituted. Injectable and intranasal calcitonin therapy prevents bone loss and increases bone density in the vertebral spine in postmenopausal women with osteoporosis; some studies have shown a reduction in future vertebral fracture with use. Guidelines generally recommend against calcitonin for the treatment of osteoporosis; the efficacy of calcitonin in preventing non-vertebral fractures is not established, and the increase in bone mineral density is less than that reported for other agents (e.g., bisphosphonates). Calcitonin may be considered for women who can not or will not take more effective agents; use within 5 years of menopause onset is not recommended as benefit/efficacy has not been observed in early menopause. Calcitonin may reduce the pain of acute osteoporotic vertebral fractures and is sometimes used short-term for this purpose off-label, but there is no sufficient data that calcitonin is effective for chronic pain due to prior osteoporotic vertebral fractures. The potential analgesic effect of calcitonin continues to be investigated for other types of bone fracture and for patients with bone metastases due to cancer. For Paget's disease, the use of injectable calcitonin leads to partial radiographic healing of lytic lesions, but most patients do not achieve normalization of bone turnover, and thus calcitonin has limited use versus newer, more effective agents (i.e., bisphosphonates). Oral calcitonin dosage forms have been investigated, but trials have been discontinued due to lack of efficacy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Calcitonin-salmon injection is administered intramuscularly or subcutaneously. If the volume of the injection exceeds 2 mL, intramuscular injection is preferable and multiple injection sites should be used.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-With chronic use, ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.
Skin Testing prior to treatment:
-In patients with a suspected sensitivity to salmon calcitonin, a skin test using a diluted injection concentration should be performed.
-A detailed skin testing protocol is available from the manufacturer's product safety department. Healthcare providers may wish to refer patients who require skin testing to an allergist.
-Prepare testing solution in a tuberculin syringe by diluting 10 International Units (0.05 mL) of the calcitonin salmon injection to 1 mL with 0.9% Sodium Chloride injection. Mix thoroughly.
-Discard 0.9 mL of the diluted test injection and administer the remaining 0.1 mL intracutaneously on the flexor surface of the forearm.
-Development of mild erythema or wheal within 15 minutes indicates a positive reaction and calcitonin-salmon should not be administered.
Intramuscular Administration
-Inject into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel. If the volume of the injection exceeds 2 mL, the IM route is preferred and multiple injection sites should be used.
-Rotate sites of injection.
-Dispose of the used syringe and needle in an FDA-cleared sharps disposal container after use.
Subcutaneous Administration
-Subcutaneous administration is preferred for outpatient self-administration.
-If calcitonin is to be self-administered, instruct the patient and/or caregiver on aseptic technique and the proper subcutaneous injection technique.
-Inject subcutaneously taking care not to inject intradermally.
-Rotate injection sites.
-Dispose of the used syringe and needle in an FDA-cleared sharps disposal container after use.
Inhalation Administration
Intranasal Inhalation Administration
Calcitonin-salmon Nasal Spray:
-Before the first dose, the nasal spray should be at room temperature. Remove the unopened bottle from the refrigerator and allow the spray to reach room temperature.
-Remove the protective cap.
-To prime the pump bottle, the bottle should be held upright and the 2 side arms of the pump depressed toward the bottle until a full spray is produced. The pump is primed once the first full spray is emitted.
-The nasal spray pump only requires priming before the first dose.
-To administer, carefully place the nozzle into the nostril with the patient's head in the upright position. Depress the pump firmly toward the bottle.
-Alternate the nostril used for administration each day.
-To avoid the spread of infection, do not use the sprayer for more than 1 person.
-Fortical Nasal Spray Storage: After opening, store bottle in use in an upright position at 20 to 25 degrees C (68 to 77 degrees F). Discard the bottle after 30 doses.
-Miacalcin Nasal Spray Storage (or generic equivalent): After opening, store bottle in use at room temperature between 20 and 25 degrees C (68 and 77 degrees F) in an upright position, for up to 35 days. Each bottle contains at least 30 doses. Discard the bottle after 30 doses.
-Ensure adequate intake of calcium and vitamin D during osteoporosis treatment and prevention.
Because salmon calcitonin is a foreign protein, allergic reactions may occur. Serious allergic symptoms have developed in susceptible individuals, including anaphylactic shock, angioedema, such as swelling of the tongue or throat, laryngeal edema, bronchospasm, and very rarely, death due to anaphylaxis. Anaphylaxis and anaphylactic shock are rare, reported in < 1% of patients during clinical trials of calcitonin nasal spray, while bronchospasm occurred in up to 3% of patients. A local inflammatory injection site reaction (10%) has been reported at the site of subcutaneous or intramuscular injection. In susceptible individuals, skin testing should be performed prior to salmon-calcitonin treatment. Evidence of anaphylactoid reactions to the hormone, including skin rash (unspecified) (1-3%), urticaria, pruritus, or the above-mentioned symptoms, requires medical attention and, possibly, emergency measures. Erythematous rash has been noted in 1-3% of patients, and pruritus in < 1%. Other adverse dermatologic or hypersensitivity effects associated with calcitonin therapy include flushing or hypotension. Allergic reactions should be differentiated from generalized flushing of face or hands or hypotension. Flushing occurred in 2-5% of patients treated with calcitonin injection compared to < 1% in patients treated with intranasal calcitonin. The nasal dosage form has a mean bioavailability of 3%; therefore, less systemic drug circulation may account for the lower frequency of flushing with the nasal spray. Other rare dermatologic reactions to calcitonin reported in < 1% of patients include skin ulcer, eczema, and alopecia.
Lymphadenopathy and infection (types unspecified) were associated with calcitonin use in clinical trials, occurring in up to 3% of patients. Anemia was noted in < 1% of patients.
Postmenopausal osteoporotic patients using intranasal calcitonin during clinical studies experienced various nasal symptoms. These symptoms occurred in 10.6% of patients (n = 341), and included nasal dryness or crusts, redness or erythema, nasal sores, nasal irritation, itching, thick feelings or blocked nasal passages, soreness, pallor, infection, stenosis, small or bleeding wounds, tenderness, sores across the bridge of the nose, or other uncomfortable feelings. Nasal symptoms were mild in 70% of patients, moderate in 25%, and severe in 5%. Rhinitis was reported in 12% of patients, and allergic rhinitis or ulcerative rhinitis were observed in < 1%. Epistaxis was observed in 3.5% of patients, and sinusitis and upper respiratory tract infections were reported in up to 3%. Rare reports (< 1%) of parosmia, nasal congestion, sneezing, allergic rhinitis, nasal odor, and mucosal excoriation, pharyngitis, bronchitis, pneumonia, cough, and dyspnea were noted. Nasal symptoms were often only reported once and usually improved with continued use or discontinuation. Furthermore, the reported incidence of nasal adverse events (rhinitis, irritation, erythema, and excoriation) is higher in patients over the age of 65, particularly those over the age of 75 in one study of 942 patients, of which approximately 50% were 65-74 years of age and approximately 20% were >= 75 years of age. Nasal examinations should be performed prior to and during treatment with calcitonin nasal spray. If nasal mucosa ulceration occurs, the drug may be discontinued to promote healing.
Nausea and vomiting occurred in about 10% of patients receiving salmon-calcitonin injection and only 1.8% of patients receiving intranasal calcitonin during clinical studies. The nasal dosage form has a mean bioavailability of 3%; therefore, less systemic drug circulation may account for the lower frequency of nausea and vomiting with the nasal spray. These effects are more evident during the initial treatment with the hormone and may subside with continued treatment. Adverse gastrointestinal symptoms that occurred in 1-3% of patients include abdominal pain, constipation, diarrhea, and dyspepsia. Flatulence, appetite stimulation, gastritis, thirst, weight gain, xerostomia, and dysgeusia (or salty taste) were reported in < 1% of patients.
Headache was the most frequently occurring neurologic reaction associated with calcitonin during clinical trials, occurring in 3.2% of patients who received the nasal spray formulation. Dizziness and paresthesias were noted in up to 3% of patients, while vertigo, migraine, neuralgia, tremor, and agitation were reported rarely (< 1%). Psychiatric reactions to calcitonin include depression (1-3%), insomnia (< 1%), anxiety (< 1%), and anorexia (< 1%).
Hypocalcemia can occur during treatment with calcitonin. Severe hypocalcemia associated with tetany (i.e., muscle cramps, twitching) and seizures has been reported. Patients should be monitored for hypocalcemia and symptoms of hypocalcemia, regardless of the indication for calcitonin.
Antibody formation to calcitonin-salmon has been reported with calcitonin-salmon nasal spray and the injection, and appears to be common. Consider the possibility of antibody formation in any patient with an initial response to the drug that later stops responding to treatment. Circulating antibodies to calcitonin-salmon have been reported after 2 to 18 months of treatment in about 50% of patients with Paget's disease in whom antibody studies were performed; calcitonin remained effective in many cases. In a 2-year calcitonin-salmon nasal spray clinical study that evaluated immunogenicity, a measurable antibody titer was found in 69% of patients treated with calcitonin-salmon nasal spray vs. 3% of placebo-treated patients. Occasionally, patients with antibodies may have a decreased response or loss of response to calcitonin for their condition. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of a positive antibody test result may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of antibodies among different calcitonin-salmon products may be misleading.
Cardiovascular adverse reactions to calcitonin reported in up to 3% of patients (n = 341) during clinical trials with the nasal spray formulation include hypertension and angina. Sinus tachycardia, palpitations, bundle-branch block, myocardial infarction, stroke, and thrombo-phlebitis were observed rarely, in < 1% of patients.
Back pain and arthralgia occurred in 5% and 3.8% of patients, respectively, who received calcitonin nasal spray during clinical trials. Arthrosis and myalgia occurred in 1-3% of patients, while arthritis, polymyalgia rheumatica, and body stiffness occurred rarely (< 1%). Most of the reactions were mild to moderate in severity. Musculoskeletal pain has also been observed with the injectable formulation.
Metabolic related adverse reactions to calcitonin are rare. Cholelithiasis, hepatitis, goiter, and hyperthyroidism were reported in < 1% of patients (n = 341) during clinical trials with calcitonin nasal spray.
Cystitis was reported in up to 3% of patients during clinical trials with calcitonin nasal spray, while pyelonephritis, hematuria, and nephrolithiasis were reported in less than 1%. Nocturia and polyuria have also been associated with calcitonin use. Coarse granular casts and casts containing renal tubular epithelial cells were reported in young adult volunteers at bed rest who were given injectable salmon calcitonin. There was no evidence of renal abnormality and the urine sediment became normal after calcitonin was stopped. Periodic examinations of urine sediment are recommended in treated patients.
Influenza-like symptoms have been associated with calcitonin use. These symptoms, along with fatigue, occurred in 1-3% of patients given calcitonin during clinical trials. Fever, diaphoresis, generalized edema, and peripheral edema were noted in < 1% of patients.
Conjunctivitis and abnormal ocular lacrimation were the most frequently reported ocular adverse reactions to calcitonin during clinical trials, with incidence rates of 1-3%. Blurred vision, vitreous floater, and other unspecified visual disturbances occurred in < 1% of patients. Ocular pain has also been reported. Hearing and vestibular adverse reactions are rare, with tinnitus, hearing loss, and otalgia (earache) reported in < 1% of patients.
Consider the potential benefits of therapy against risks and periodically re-evaluate the continued need for therapy due to the possible association of calcitonin-salmon therapy and new primary malignancy. An increased incidence of malignancy among calcitonin-salmon-treated patients (4.1%) compared with placebo-treated patients (2.9%) was found in a meta-analysis of 21 randomized, controlled clinical trials with calcitonin-salmon (nasal spray or investigational oral formulations). An increased risk of malignancy cannot be excluded when calcitonin-salmon is administered long-term by other routes (subcutaneously, intramuscularly, or intravenously).
Calcitonin-salmon is a synthetic polypeptide of amino acids comparable to the natural calcitonin of salmon origin and is contraindicated for use in patients with a salmon calcitonin or fish hypersensitivity. Serious hypersensitivity reactions have been reported in patients receiving calcitonin-salmon nasal spray (e.g., bronchospasm, swelling of the tongue or throat, anaphylaxis and anaphylactic shock). Reports of serious hypersensitivity reactions with injectable calcitonin-salmon have also been reported, including reports of death attributed to anaphylaxis. The usual provisions should be made for emergency treatment if such a reaction occurs. Hypersensitivity reactions should be differentiated from generalized flushing and hypotension. For patients with a suspected hypersensitivity to calcitonin-salmon, skin testing should be considered prior to treatment. Healthcare providers may wish to refer patients who require skin testing to an allergist. A detailed skin testing protocol is available from the manufacturers; consult the specific prescribing information for contact information for the skin testing protocol.
Hypocalcemia associated with tetany and seizure activity has been reported with calcitonin therapy. Correct hypocalcemia and any other disorders affecting mineral metabolism (e.g., vitamin D deficiency) before administration of calcitonin. Monitor serum calcium and symptoms of hypocalcemia in patients with a history of hypocalcemia or a mineral metabolism disorder. Ensure adequate intake of calcium (at least 1,000 mg elemental calcium per day) and vitamin D (at least 10 mcg or 400 International Units per day) during calcitonin therapy.
Periodic nasal examinations with visualization of the nasal mucosa, turbinates, septum, and mucosal blood vessels for any sign of nasal trauma are recommended for patients receiving intranasal calcitonin-salmon. The majority of patients in whom nasal abnormalities were noted also reported nasal complaints/symptoms as adverse events. Therefore, a nasal examination should be performed prior to the start of treatment with nasal calcitonin and at anytime nasal complaints occur. If severe ulceration of the nasal mucosa occurs, calcitonin nasal spray should be discontinued. Although smaller ulcers often heal without withdrawal of calcitonin nasal spray, the medication should be discontinued temporarily until healing occurs.
The reported overall incidence of new primary malignancy was higher among calcitonin-salmon-treated patients (4.1%) compared with placebo-treated patients (2.9%) in a meta-analysis of 21 randomized, controlled clinical trials with calcitonin-salmon (nasal spray or investigational oral formulations). The data suggest an increased risk of malignancies in calcitonin-salmon-treated patients compared to placebo-treated patients. It is not possible to exclude an increased risk when calcitonin-salmon is administered long-term subcutaneously or intramuscularly. Carefully consider the benefits for the individual patient against the possible risks.
Calcitonin-salmon should be used during pregnancy only if the potential benefit justifies the use versus potential risks to the patient or fetus. There are no adequate studies of calcitonin-salmon injection during pregnancy to inform a drug associated risk for birth defects or miscarriage. Based on animal data, calcitonin-salmon nasal spray is predicted to have a low probability of increasing the risk of adverse developmental outcomes above background risk. When studied in rabbits, salmon calcitonin-salmon decreased fetal birth weights when given by subcutaneous injection in doses 4 to 18 times the recommended human parenteral dose and 70 to 278 times the recommended human intranasal dose (based on body surface area). No embryo/fetal toxicities related to calcitonin-salmon were reported from maternal subcutaneous daily calcitonin-salmon doses in rats up to 80 International Units/kg/day from gestation day 6 to 15.
Use calcitonin with caution during breast-feeding. There is no information on the presence of calcitonin in human milk, the effects on the breast-fed infant, or the effects on milk production. Calcitonin-salmon has been shown to inhibit lactation in rats. Due to species-specific differences in lactation physiology, animal data may not reliably predict human response. Human milk naturally contains some calcitonin and its precursor, procalcitonin. Because it is a large peptide, any systemic absorption by the infant is unlikely because it is probably destroyed in the infant's gastrointestinal tract. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for calcitonin and any potential adverse effects on the breast-fed infant from calcitonin or the underlying maternal condition.
In a large multi-centered, double-blind, randomized clinical study of 942 patients using calcitonin-salmon nasal spray, geriatric patients age 65 to 74 years old accounted for 49.5% of patients and those aged 75 years or more accounted for 21%. Compared to younger adults, the incidence of nasal adverse events (rhinitis, irritation, erythema, and excoriation) was higher in patients over 65 years of age, particularly those over the age of 75 years. Most events were mild in intensity. Other reported clinical experience with calcitonin-salmon injection or nasal sprays has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Recommendations for calcium and vitamin D intake:-To promote general bone health, guidelines for the prevention and treatment of osteoporosis recommend a target daily intake of 1,200 mg of elemental calcium for females older than 50 years and males older than 70 years. Target daily elemental calcium intake for males 70 years or younger is 1,000 mg. Daily vitamin D intake of 20 to 25 mcg (800 to 1,000 international units) is recommended for patients 50 years of age and older.
For the treatment of hypercalcemia:
Intramuscular and Subcutaneous dosage:
Adults: Initially, 4 International Units/kg given IM or subcutaneously every 12 hours. If the response is not satisfactory after 1 to 2 days, increase the dose to 8 International Units/kg IM or subcutaneously every 12 hours. May further titrate. Max: 8 International Units/kg IM or subcutaneously every 6 hours. Decreases in serum calcium are usually noted within 2 hours of a single dose; however, the hypocalcemic response to calcitonin therapy usually only lasts 4 to 7 days despite continued therapy.
For the treatment of moderate to severe symptomatic Paget's disease:
Intramuscular or Subcutaneous dosage (calcitonin-salmon injection):
Adults: 100 International Units given IM or subcutaneously once daily is the recommended dose. Per treatment guidelines for Paget's disease, the use of injectable calcitonin-salmon leads to partial radiographic healing of lytic lesions, but most patients do not achieve normalization of bone turnover, and thus calcitonin has limited use versus newer, more effective agents (i.e., bisphosphonates). Calcitonin should be used only in patients who do not respond to alternative treatments or for whom such treatments are not suitable (e.g., patients for whom other therapies are contraindicated or for patients who are intolerant or unwilling to use other therapies).
For the treatment of osteoporosis in postmenopausal women who are more than 5 years past menopause:
Intramuscular or Subcutaneous dosage (calcitonin-salmon injection):
Adult Postmenopausal Females: 100 International Units IM or subcutaneously once daily. Give with supplemental calcium and vitamin D if dietary intake is inadequate. Reserve use for patients that are more than 5 years postmenopause in whom alternative treatments are not suitable (e.g., patients for whom other therapies are contraindicated or for patients who are intolerant or unwilling to use other therapies). A controlled study, which was prematurely discontinued, failed to demonstrate any benefit of calcitonin-salmon on fracture rate. Guidelines recommend against calcitonin-salmon for the treatment of osteoporosis; the efficacy of calcitonin in preventing vertebral and non-vertebral fractures is not established, and the increase in bone mineral density observed is less than that reported for other agents (e.g., bisphosphonates). Calcitonin may be considered for women who can not or will not take more effective agents; do not prescribe in early menopause as benefit/efficacy has not been observed within the first 5 years of menopause onset.
Intranasal dosage (calcitonin-salmon nasal spray 200 International Units/spray):
Adult Postmenopausal Females: 200 International Units (1 spray) intranasally in 1 nostril once daily. Give supplemental calcium and vitamin D if dietary intake is inadequate. Alternate the nostril used daily. Fracture reduction efficacy has not been demonstrated. Reserve use for patients that are more than 5 years postmenopause in whom alternative treatments are not suitable (e.g., patients for whom other therapies are contraindicated or for patients who are intolerant or unwilling to use other therapies). The PROOF study indicates a potential reduction in new vertebral fractures with use. Guidelines recommend against calcitonin-salmon for the treatment of osteoporosis; the efficacy of calcitonin in preventing non-vertebral fractures is not established, and the increase in bone mineral density observed is less than that reported for other agents (e.g., bisphosphonates). Calcitonin may be considered for women who can not or will not take more effective agents; do not prescribe in early menopause as benefit/efficacy has not been observed within the first 5 years of menopause onset.
For the acute management of bone pain* due to an acute osteoporotic vertebral fracture:
Intranasal, Subcutaneous, or Intramuscular dosage:
Adults: Safety and efficacy not established; off-label use reported. 100 International Units calcitonin-salmon injection given IM or subcutaneously once daily or 200 International Units (1 spray of nasal spray) intranasally in 1 nostril once daily, given for up to 30 days post event, have provided symptomatic relief and facilitated mobility in small studies. For short-term use only. Although calcitonin may help relieve acute back pain associated with a recent osteoporotic vertebral compression fracture, one metanalysis found that there is no sufficient data for effectiveness against chronic pain associated with older vertebral fracture.
For the treatment of complex regional pain syndrome*:
Intranasal dosage:
Adults: 100 to 300 units/day intranasally.
Maximum Dosage Limits:
-Adults
200 International Units/day intranasally for osteoporosis; 100 International Units IM or subcutaneously for most indications; for acute hypercalcemia, up to 32 international units/kg/day IM or subcutaneously.
-Geriatric
200 International Units/day intranasally for osteoporosis; 100 International Units IM or subcutaneously for most indications; for acute hypercalcemia, up to 32 international units/kg/day IM or subcutaneously.
-Adolescents
Safety and efficacy have not been established; off-label use reported for selected conditions.
-Children
Safety and efficacy have not been established; off-label use reported for selected conditions.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Calcifediol: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, vitamin D preparations should be avoided. Vitamin D analogs can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of vitamin D is necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcitriol: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, vitamin D preparations should be avoided. Vitamin D analogs can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of vitamin D is necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Acetate: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Carbonate: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Carbonate; Simethicone: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Chloride: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium Gluconate: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcium; Vitamin D: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Chromium: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Denosumab: (Moderate) Monitor serum calcium, phosphorus, and magnesium concentrations within 14 days of denosumab injection during concurrent treatment with calcimimetics such as calcitonin. The risk for hypocalcemia and other disturbances of mineral metabolism may increase during coadministration. Monitor serum calcium concentrations closely in patients with severe renal impairment (CrCl less than 30 mL/minute) or renal failure (and/or on dialysis) receiving calcimimetics. An increased risk of hypocalcemia was seen in clinical trials involving patients with renal dysfunction. Instruct patients to seek medical care if symptoms of hypocalcemia develop.
Doxercalciferol: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, vitamin D preparations should be avoided. Vitamin D analogs can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of vitamin D is necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Lithium: (Moderate) Reduced serum lithium concentrations have been observed in previously stabilized patients who initiated daily calcitonin salmon subcutaneous injections for osteoporosis. The mechanism is not clear, but serum lithium concentrations were reduced to 30% of the baseline value in all patients studied, and fell below normal therapeutic ranges. Increased urinary lithium clearance is a proposed mechanism for the interaction.
Paricalcitol: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, vitamin D preparations should be avoided. Vitamin D analogs can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of vitamin D is necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Pyridoxine, Vitamin B6: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Vitamin D analogs: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, vitamin D preparations should be avoided. Vitamin D analogs can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of vitamin D is necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Vitamin D: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcitonin is a is a peptide hormone secreted by the C-cells of the thyroid gland endogenously; calcitonin-salmon is a calcitonin receptor agonist. Calcitonin acts primarily on bone, but direct renal effects and actions on the gastrointestinal tract are also recognized. Calcitonin-salmon appears to have actions essentially identical to endogenous calcitonin of mammalian origin, but its potency per mg is greater than endogenous calcitonin, and it has a longer duration of action. The actions of calcitonin on bone and its role in normal human bone physiology are still not completely elucidated, although calcitonin receptors have been discovered in osteoclasts and osteoblasts.
Calcitonin is a hypocalcemic hormone whose effects are generally opposite those of parathyroid hormone (PTH). Calcitonin helps maintain calcium homeostasis. Secretion of calcitonin is regulated by serum calcium; high serum calcium increases the release of calcitonin. Catecholamines, glucagon, gastrin, or cholecystokinin may stimulate calcitonin secretion. Calcitonin directly inhibits osteoclasts, binding to plasma membrane receptors and increasing intracellular cyclic adenosine monophosphate (cAMP), as well as interfering with the membrane transport mechanisms of phosphate and calcium. Calcitonin lowers serum calcium concentrations by inhibiting bone resorption with subsequent decreases in elevated serum alkaline phosphatase concentrations and urinary hydroxyproline levels. The release of calcium and phosphate from bone is reduced, and the extent of collagen breakdown is decreased. Calcitonin antagonizes the actions of PTH, but concentrations of PTH do not increase significantly in response to calcitonin therapy. Calcitonin also has activity outside the bone. In the kidney, calcitonin increases the excretion of filtered phosphate, calcium, and sodium by decreasing their tubular reabsorption. In some patients, the inhibition of bone resorption is of such a magnitude that the consequent of reduction of filtered calcium load more than compensates for the decrease in tubular reabsorption of calcium. The result is a decrease in urinary calcium. Short-term administration results in a marked transient decrease in the volume and acidity of gastric secretions and the volume and the trypsin and amylase content of pancreatic secretions.
Calcitonin has an antinociceptive activity that is independent of its action on bone resorption; the mechanism is not explicitly known. The analgesic effect appears to be evident for acute vertebral fractures due to osteoporosis; there is no sufficient evidence that the drug has effectiveness for pain due to prior fracture.
Calcitonin is given parenterally (preferably by subcutaneous or intramuscular injection) or intranasally since calcitonin is destroyed in the GI tract.
It is not known whether calcitonin crosses the blood-brain barrier or if it distributes into breast milk. Calcitonin does not appear to cross the placenta. The metabolic fate of calcitonin has not been clearly established, but it is believed to be rapidly degraded by the kidneys, blood, and peripheral tissues into smaller inactive fragments. The half-life of salmon calcitonin is about 1 hour. Elimination half-life of intranasal salmon calcitonin is approximately 43 minutes. Calcitonin is excreted primarily in the urine as inactive metabolites.
-Route-Specific Pharmacokinetics
Intravenous Route
Onset of action of calcitonin is immediate following IV administration. Peak effects are observed within 4 hours after parenteral administration. The duration of effect is 0.5-12 hours after IV administration.
Intramuscular Route
Following IM administration, calcitonin is absorbed directly into the systemic circulation and the onset of action begins within 15 minutes. Peak effects are observed within 4 hours after parenteral administration. The duration of effect is 8-24 hours after intramuscular administration.
Subcutaneous Route
Following subcutaneous administration, calcitonin is absorbed directly into the systemic circulation and the onset of action begins within 15 minutes. Peak effects are observed within 4 hours after parenteral administration. The duration of effect is 8-24 hours after subcutaneous administration.
Other Route(s)
Intranasal Route
Absorption through the nasal mucosa is rapid, with peak plasma concentrations achieved in 31-39 minutes. The bioavailability of intranasal calcitonin-salmon appears to be variable. In normal volunteers, bioavailability of the intranasal formulation compared to the parenteral product is 3%, with a range of 0.3-30.6%.
-Special Populations
Gender Differences
The pharmacokinetic parameters of intranasal salmon calcitonin administration have not been studied in postmenopausal women.