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Miacalcin

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Miacalcin




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypersensitivity Reactions

Serious hypersensitivity reactions have been reported in patients receiving Miacalcin injection, e.g., bronchospasm, swelling of the tongue or throat, anaphylactic shock, and death due to anaphylaxis. Appropriate medical support and monitoring measures should be readily available when Miacalcin injection is administered. If anaphylaxis or other severe hypersensitivity/allergic reactions occur, initiate appropriate treatment [see CONTRAINDICATIONS].

For patients with suspected hypersensitivity to calcitonin-salmon, skin testing should be considered prior to treatment utilizing a dilute, sterile solution of Miacalcin injection. Healthcare providers may wish to refer patients who require skin testing to an allergist. A detailed skin testing protocol is available from the Medical Services Department of Novartis Pharmaceuticals Corporation.

Hypocalcemia

Hypocalcemia associated with tetany (i.e., muscle cramps, twitching) and seizure activity has been reported with Miacalcin injection therapy. Hypocalcemia must be corrected before initiating therapy. Other disorders affecting mineral metabolism (such as vitamin D deficiency) should also be effectively treated. In patients at risk for hypocalcemia, provisions for parenteral calcium administration should be available during the first several administrations of calcitoninsalmon and serum calcium and symptoms of hypocalcemia should be monitored. Use of Miacalcin injection for the treatment of Paget's disease or postmenopausal osteoporosis is recommended in conjunction with an adequate intake of calcium and vitamin D [see DOSAGE AND ADMINISTRATION].

Malignancy

In a meta-analysis of 21 randomized, controlled clinical trials with calcitonin-salmon (nasal spray or investigational oral formulations), the overall incidence of malignancies reported was higher among calcitonin-salmon-treated patients (4.1%) compared with placebo-treated patients (2.9%). This suggests an increased risk of malignancies in calcitonin-salmontreated patients compared to placebo-treated patients. It is not possible to exclude an increased risk when calcitoninsalmon is administered long-term subcutaneously, intramuscularly, or intravenously. The benefits for the individual patient should be carefully considered against possible risks [see ADVERSE REACTIONS].

Antibody Formation

Circulating antibodies to calcitonin-salmon have been reported with Miacalcin injection. The possibility of antibody formation should be considered in any patient with an initial response to Miacalcin injection who later stops responding to treatment [see ADVERSE REACTIONS].

Urine Sediment Abnormalities

Coarse granular casts and casts containing renal tubular epithelial cells were reported in young adult volunteers at bed rest who were given injectable calcitonin-salmon to study the effect of immobilization on osteoporosis. There was no other evidence of renal abnormality and the urine sediment normalized after calcitonin-salmon was stopped. Periodic examinations of urine sediment should be considered.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity

The incidence of pituitary adenomas was increased in rats after one and two years of subcutaneous exposure to synthetic calcitonin-salmon. The significance of this finding to humans is unknown because pituitary adenomas are very common in rats as they age, the pituitary adenomas did not transform into metastatic tumors, there were no other clear treatment-related neoplasms, and synthetic calcitonin-salmon related neoplasms were not observed in mice after two years of dosing.

Rat findings

The only clear neoplastic finding in rats dosed subcutaneously with calcitonin-salmon was an increase in the incidence of pituitary adenomas in male Fisher 344 rats and female Sprague Dawley rats after one year of dosing and male Sprague Dawley rats dosed for one and two years. In female Sprague Dawley rats, the incidence of pituitary adenomas after two years was high in all treatment groups (between 80% and 92% including the control groups) such that a treatment-related effect could not be distinguished from natural background incidence. The lowest dose in male Sprague Dawley rats that developed an increased incidence of pituitary adenomas after two years of dosing (1.7 International Units/kg/day) is approximately 1/6thof the maximum recommended subcutaneous dose in humans (100 International Units/day) based on body surface area conversion between rats and humans. The findings suggest that calcitonin-salmon reduced the latency period for development of non-functioning pituitary adenomas.

Mouse findings

No carcinogenicity potential was evident in male or female mice dosed subcutaneously for two years with synthetic calcitonin-salmon at doses up to 800 International Units/kg/day. The 800 International Units/kg/day dose is approximately 39 times the maximum recommended subcutaneous dose in humans (100 International Units/day) based on body surface area conversion between mice and humans.

Mutagenesis

Synthetic calcitonin-salmon tested negative for mutagenicity using Salmonella typhimurium (5 strains) and Escherichia coli (2 strains), with and without rat liver metabolic activation, and was not clastogenic in a chromosome aberration test in Chinese Hamster V79 cells. There was no evidence that calcitonin-salmon was clastogenic in the in vivo mouse micronucleus test.

Fertility

Effects of calcitonin-salmon on fertility have not been assessed in animals.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Risk Summary

There are no adequate and well-controlled studies in pregnant women. Miacalcin injection should be used during pregnancy only if the potential benefit justifies the use as compared with potential risks to the patient and fetus. Based on animal data, Miacalcin is predicted to have low probability of increasing the risk of adverse developmental outcomes above background risk.

Animal Data

Calcitonin-salmon has been shown to cause a decrease in fetal birth weights in rabbits when given by subcutaneous injection in doses 4-18 times the parenteral dose recommended for human use (of 54 International Units/m²).

No embryo/fetal toxicities related to Miacalcin were reported from maternal subcutaneous daily doses in rats up to 80 International Units /kg/day from gestation day 6 to 15.

Nursing Mothers

It is not known whether this drug is excreted in human milk. No studies have been conducted to assess the impact of Miacalcin on milk production in humans, its presence in human breast milk, or its effects on the breastfed child. Because many drugs are excreted in human milk, caution should be exercised when Miacalcin is administered to a nursing woman. Calcitonin has been shown to inhibit lactation in rats.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Miacalcin injection did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 2/23/2015
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions

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