WARNINGS
ALLERGIC REACTIONS
Because calcitonin is a polypeptide, the possibility of a systemic allergic reaction exists. A few cases of allergic-type reactions have been reported in patients receiving Miacalcin® (calcitonin-salmon) Nasal Spray, including one case of anaphylactic shock, which appears to have been due to the preservative because the patient could tolerate injectable calcitonin-salmon without incident. With injectable calcitonin-salmon there have been a few reports of serious allergic-type reactions (e.g., bronchospasm, swelling of the tongue or throat, anaphylactic shock, and in one case death attributed to anaphylaxis). The usual provisions should be made for the emergency treatment of such a reaction should it occur. Allergic reactions should be differentiated from generalized flushing and hypotension.
For patients with suspected sensitivity to calcitonin, skin testing should be considered prior to treatment utilizing a dilute, sterile solution of Miacalcin® Injection, Synthetic. Physicians 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.
PRECAUTIONS
1. DRUG INTERACTIONS
Formal studies designed to evaluate drug interactions with calcitonin-salmon have not been done. No drug interaction studies have been performed with Miacalcin® (calcitonin-salmon) Nasal Spray ingredients.
Currently, no drug interactions with calcitonin-salmon have been observed. The effects of prior use of diphosphonates in postmenopausal osteoporosis patients have not been assessed; however, in patients with Paget's Disease prior diphosphonate use appears to reduce the anti-resorptive response to Miacalcin® Nasal Spray.
2. PERIODIC NASAL EXAMINATIONS
Periodic nasal examinations with visualization of the nasal mucosa, turbinates, septum and mucosal blood vessel status are recommended.
The development of mucosal alterations or transient nasal conditions occurred in up to 9% of patients who received Miacalcin® Nasal Spray and in up to 12% of patients who received placebo nasal spray in studies in postmenopausal females. The majority of patients (approximately 90%) in whom nasal abnormalities were noted also reported nasally related complaints/symptoms as adverse events. Therefore, a nasal examination should be performed prior to start of treatment with nasal calcitonin and at any time nasal complaints occur.
In all postmenopausal patients treated with Miacalcin® Nasal Spray, the most commonly reported nasal adverse events included rhinitis (12%), epistaxis (3.5%), and sinusitis (2.3%). Smoking was shown not to have any contributory effect on the occurrence of nasal adverse events. One patient (0.3%) treated with Miacalcin® Nasal Spray who was receiving 400 I.U. daily developed a small nasal wound. In clinical trials in another disorder (Paget's Disease), 2.8% of patients developed nasal ulcerations.
If severe ulceration of the nasal mucosa occurs, as indicated by ulcers greater than 1.5 mm in diameter or penetrating below the mucosa, or those associated with heavy bleeding, Miacalcin® Nasal Spray should be discontinued. Although smaller ulcers often heal without withdrawal of Miacalcin® Nasal Spray, medication should be discontinued temporarily until healing occurs.
3. INFORMATION FOR PATIENTS
Careful instructions on pump assembly, priming of the pump and nasal introduction of Miacalcin® Nasal Spray should be given to the patient. Although instructions for patients are supplied with individual bottles, procedures for use should be demonstrated to each patient. Patients should notify their physician if they develop significant nasal irritation.
Patients should be advised of the following:
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Store new, unassembled bottles in the refrigerator between 2°C-8°C (36°F-46°F).
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Protect the product from freezing.
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Before priming the pump and using a new bottle, allow it to reach room temperature.
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Store bottle in use at room temperature between 15°C-30°C (59°F-86°F) in an upright position, for up to 35 days. Each bottle contains at least 30 doses.
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See DOSAGE AND ADMINISTRATION, Priming (Activation) of Pump for complete instructions on priming the pump and administering Miacalcin® Nasal Spray.
You should keep track of the number of doses used from the bottle.
After 30 doses, each spray may not deliver the correct amount of medication, even if the bottle is not completely empty.
4. CARCINOGENICITY, MUTAGENICITY, AND IMPAIRMENT OF FERTILITY
An increased incidence of non-functioning pituitary adenomas has been observed in one-year toxicity studies in Sprague-Dawley and Fischer 344 Rats administered (subcutaneously) calcitonin-salmon at dosages of 80 I.U. per kilogram per day (16-19 times the recommended human parenteral dose and about 130-160 times the human intranasal dose based on body surface area). The findings suggest that calcitonin-salmon reduced the latency period for development of pituitary adenomas that do not produce hormones, probably through the perturbation of physiologic processes involved in the evolution of this commonly occurring endocrine lesion in the rat. Although administration of calcitonin-salmon reduces the latency period of the development of nonfunctional proliferative lesions in rats, it did not induce the hyperplastic/neoplastic process.
Calcitonin-salmon was tested for mutagenicity using Salmonella typhimurium (5 strains) and Escherichia coli (2 strains), with and without rat liver metabolic activation, and found to be non-mutagenic. The drug was also not mutagenic in a chromosome aberration test in mammalian V79 cells of the Chinese Hamster in vitro.
5. LABORATORY TESTS
Urine sediment abnormalities have not been reported in ambulatory volunteers treated with Miacalcin® Nasal Spray. Coarse granular 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 evidence of renal abnormality and the urine sediment became normal after calcitonin was stopped. Periodic examinations of urine sediment should be considered.
6. PREGNANCY
TERATOGENIC EFFECTS
Category C
Calcitonin-salmon has been shown to cause a decrease in fetal birth weights in rabbits when given by injection in doses 8-33 times the parenteral dose and 70-278 times the intranasal dose recommended for human use based on body surface area.
Since calcitonin does not cross the placental barrier, this finding may be due to metabolic effects on the pregnant animal. There are no adequate and well controlled studies in pregnant women with calcitonin-salmon. Miacalcin® Nasal Spray is not indicated for use in pregnancy.
7. NURSING MOTHERS
It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on this drug since many drugs are excreted in human milk. Calcitonin has been shown to inhibit lactation in animals.
8. GERIATRIC USE
Clinical trials using Miacalcin® Nasal Spray have included postmenopausal patients up to 77 years of age. No unusual adverse events or increased incidence of common adverse events have been noted in patients over 65 years of age.
9. PEDIATRIC USE
There are no data to support the use of Miacalcin® Nasal Spray in children. Disorders of bone in children referred to as idiopathic juvenile osteoporosis have been reported rarely. The relationship of these disorders to postmenopausal osteoporosis has not been established and experience with the use of calcitonin in these disorders is very limited.
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