Calcitonin salmon

Description

Calcitonin is a polypeptide hormone secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish. Calcitonin Salmon (synthetic origin) Nasal Spray is a synthetic polypeptide consisting of 32 amino acids arranged in the same linear sequence as calcitonin derived from salmon. This formulation is available in a 2 mL or 3.7 mL fill glass bottle as a solution intended for nasal administration. The active ingredient is calcitonin salmon at a concentration of 2200 USP Calcitonin Salmon Units per mL, which corresponds to 200 USP Calcitonin Salmon Units per 0.09 mL actuation. Inactive ingredients include benzalkonium chloride, hydrochloric acid (added as necessary to adjust pH), purified water, and sodium chloride.

Uses and Indications

Calcitonin Salmon (synthetic origin) Nasal Spray is indicated for the treatment of postmenopausal osteoporosis in women who are more than 5 years postmenopause when alternative treatments are not suitable.

Limitations of Use: The efficacy of Calcitonin Salmon Nasal Spray in reducing fractures has not been demonstrated.

There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

For intranasal administration, the recommended dosage is one spray, delivering 200 USP Calcitonin Salmon Units, once daily. Patients should alternate nostrils with each administration to optimize absorption and minimize irritation.

Before the initial use, it is essential to allow the bottle to reach room temperature and to prime the pump to ensure proper delivery of the medication. Additionally, healthcare professionals should advise patients to maintain adequate intake of calcium and vitamin D to support overall treatment efficacy.

Contraindications

Use of this product is contraindicated in patients with hypersensitivity to calcitonin salmon or any of the excipients. Due to the potential for severe allergic reactions, administration in these individuals may pose significant health risks.

Warnings and Precautions

Serious hypersensitivity reactions, including anaphylactic shock, have been reported in patients receiving calcitonin salmon. It is advisable to consider skin testing prior to initiating treatment in individuals with a suspected hypersensitivity to this medication.

Patients should be monitored for hypocalcemia, which has been documented in some cases. To mitigate this risk, it is essential to ensure adequate intake of calcium and vitamin D throughout the course of treatment.

Nasal adverse reactions, such as severe ulceration, may occur. Therefore, periodic nasal examinations are recommended to assess the integrity of the nasal mucosa and to identify any potential complications early.

There is an observed association between calcitonin salmon treatment and an increased risk of overall malignancies, as indicated by a meta-analysis of 21 clinical trials. Healthcare professionals should remain vigilant regarding this potential risk when prescribing calcitonin salmon.

Additionally, the development of circulating antibodies to calcitonin salmon may occur, which could lead to a diminished therapeutic response. Regular monitoring of treatment efficacy is recommended to identify any loss of response that may necessitate a reassessment of the treatment plan.

Side Effects

Adverse reactions associated with calcitonin salmon include both common and serious events.

The most frequently reported adverse reactions in patients include rhinitis, epistaxis and other nasal symptoms, back pain, arthralgia, and headache. These reactions were observed in clinical trials and are considered common among participants.

Serious adverse reactions have also been documented. Notably, serious hypersensitivity reactions, including anaphylactic shock, have been reported. It is advisable to consider skin testing prior to treatment in patients with suspected hypersensitivity to calcitonin salmon. Additionally, hypocalcemia has been reported, necessitating adequate intake of calcium and vitamin D to mitigate this risk. Nasal adverse reactions, including severe ulceration, can occur; therefore, periodic nasal examinations are recommended for monitoring.

A meta-analysis of 21 clinical trials indicates an increased risk of overall malignancies in patients treated with calcitonin salmon. Furthermore, circulating antibodies to calcitonin salmon may develop, potentially leading to a loss of response to treatment.

Patients with hypersensitivity to calcitonin salmon or any of its excipients should not use this medication. The pharmacologic actions of calcitonin salmon nasal spray suggest that hypocalcemic tetany could occur in cases of overdose; thus, provisions for parenteral administration of calcium should be readily available.

In a multi-centered, double-blind, randomized clinical study, the incidence of nasal adverse reactions, including rhinitis, irritation, erythema, and excoriation, was found to be higher in patients over the age of 65, particularly among those over the age of 75.

Drug Interactions

Concomitant use of calcitonin salmon and lithium may result in a reduction of plasma lithium concentrations. This interaction is attributed to the increased urinary clearance of lithium when both agents are administered together. Therefore, it may be necessary to adjust the dosage of lithium to maintain therapeutic levels.

No information regarding other drug and laboratory test interactions is available.

Packaging & NDC

The table below lists all NDC Code configurations of Calcitonin Salmon, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Therefore, the use of this medication in children, infants, and adolescents should be approached with caution until further data is available.

Geriatric Use

In a multi-centered, double-blind, randomized clinical study of calcitonin salmon nasal spray, a total of 467 patients aged 65 to 74 years and 196 patients aged 75 years and older were evaluated alongside 279 patients younger than 65 years. The findings indicated that elderly patients, particularly those aged 75 years and older, experienced a higher incidence of nasal adverse reactions, including rhinitis, irritation, erythema, and excoriation, compared to their younger counterparts.

While other clinical experiences have not identified significant differences in responses between geriatric patients and younger individuals, it is important to consider that some older patients may exhibit greater sensitivity to treatment. Therefore, healthcare providers should exercise caution when prescribing calcitonin salmon nasal spray to elderly patients, particularly those aged 75 years and older. Monitoring for adverse reactions is recommended, and dose adjustments may be necessary based on individual patient tolerance and response.

Pregnancy

Calcitonin salmon nasal spray is not indicated for use in females of reproductive potential. There are no available data regarding the use of calcitonin salmon nasal spray in pregnant women.

Animal reproduction studies have demonstrated that subcutaneous administration of calcitonin salmon to pregnant rabbits during organogenesis, at doses 418 times the recommended parenteral human dose, resulted in decreased fetal birth weights. In contrast, no adverse developmental outcomes were observed in rats when calcitonin salmon was administered subcutaneously at doses up to 9 times the recommended human parenteral dose based on body surface area.

Further studies in rabbits indicated that calcitonin salmon caused a decrease in fetal birth weights when administered via subcutaneous injection at doses ranging from 4 to 18 times the parenteral dose (54 International Units/m²) and 70 to 278 times the intranasal dose recommended for human use based on body surface area. However, no embryo/fetal toxicities related to calcitonin salmon nasal spray were reported from maternal subcutaneous daily doses in rats up to 80 International Units/kg/day from gestation days 6 to 15.

Given the lack of data in pregnant women and the observed effects in animal studies, healthcare professionals should exercise caution when considering the use of calcitonin salmon nasal spray in women who are pregnant or may become pregnant.

Lactation

Calcitonin salmon nasal spray is not indicated for use in females of reproductive potential. There is no information available regarding the presence of calcitonin-salmon in human milk, nor are there data on its effects on breastfed infants or on milk production in lactating mothers. However, it is important to note that calcitonin has been shown to inhibit lactation in animal studies involving rats. Therefore, caution is advised when considering the use of this medication in lactating mothers.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of overdosage with calcitonin salmon nasal spray, the pharmacologic actions indicate that hypocalcemic tetany may occur. It is essential that provisions for the parenteral administration of calcium are readily available to manage this potential complication effectively.

Clinical studies have demonstrated that single doses of calcitonin salmon nasal spray up to 1600 International Units and daily doses of up to 800 International Units for 3 consecutive days have been administered without serious adverse effects. Additionally, chronic administration of doses up to 600 International Units per day has also been evaluated without significant adverse outcomes.

Healthcare professionals should remain vigilant for symptoms of hypocalcemia and be prepared to initiate appropriate management strategies, including the administration of calcium, in the event of an overdose.

Nonclinical Toxicology

The incidence of pituitary adenomas was increased in rats following one and two years of subcutaneous exposure to synthetic calcitonin salmon. The relevance of this finding to humans remains uncertain, as pituitary adenomas are commonly observed in aging rats. Notably, these adenomas did not progress to metastatic tumors, and no other treatment-related neoplasms were identified. Furthermore, synthetic calcitonin salmon-related neoplasms were not observed in mice after two years of dosing.

In rat studies, the only significant neoplastic finding associated with subcutaneous administration of synthetic calcitonin salmon was an increased incidence of pituitary adenomas in male Fisher 344 rats and female Sprague Dawley rats after one year of treatment, as well as in male Sprague Dawley rats dosed for one and two years. In female Sprague Dawley rats, the incidence of pituitary adenomas after two years was notably high across all treatment groups (ranging from 80% to 92%, including control groups), making it difficult to distinguish a treatment-related effect from the natural background incidence. The lowest dose in male Sprague Dawley rats that exhibited an increased incidence of pituitary adenomas after two years of dosing (1.7 International Units/kg/day) is approximately twice the maximum recommended intranasal dose in humans (200 International Units/day), based on body surface area conversion and a 20-fold adjustment for reduced clinical exposure via the intranasal route. These findings suggest that calcitonin salmon may have reduced the latency period for the development of non-functioning pituitary adenomas.

In contrast, no evidence of carcinogenic potential was observed in male or female mice dosed subcutaneously for two years with synthetic calcitonin salmon at doses up to 800 International Units/kg/day. This dose is approximately 390 times the maximum recommended intranasal dose in humans (200 International Units), adjusted for body surface area and accounting for low clinical exposure via the intranasal route.

Synthetic calcitonin salmon was tested for mutagenicity and found to be negative in assays using Salmonella typhimurium (five strains) and Escherichia coli (two strains), both with and without rat liver metabolic activation. Additionally, it was not clastogenic in a chromosome aberration test conducted in Chinese Hamster V79 cells, nor was there evidence of clastogenicity in the in vivo mouse micronucleus test.

The effects of calcitonin salmon on fertility have not been evaluated in animal studies.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of Calcitonin Salmon (synthetic origin) Nasal Spray, reported voluntarily or through surveillance programs.

Allergic reactions have been noted, with some cases being serious and potentially life-threatening. Patients are advised to seek immediate medical attention if they experience symptoms indicative of an allergic reaction.

Additionally, it has been observed that Calcitonin Salmon Nasal Spray may lead to decreased calcium levels in the blood, particularly in individuals with pre-existing low blood calcium levels, which may worsen during treatment.

Nasal irritation has also been reported, especially in patients over 65 years of age. Symptoms such as crusting, dryness, redness, swelling, nose sores (ulcers), and nosebleeds should prompt patients to contact their healthcare provider promptly.

Furthermore, there is an indication that individuals using Calcitonin Salmon may have an increased risk of cancer. Regular urine testing by healthcare providers is recommended for patients undergoing treatment with Calcitonin Salmon Nasal Spray to monitor for potential complications.

Patient Counseling

Healthcare providers should instruct patients on the proper assembly of the pump, the priming process, and the correct nasal introduction of Calcitonin Salmon (synthetic origin) Nasal Spray. Although written instructions accompany each individual bottle, it is essential that healthcare providers demonstrate these procedures to ensure patient understanding and compliance.

Patients should be advised to notify their healthcare provider if they experience significant nasal irritation while using the nasal spray. It is also important to inform patients about the potential increase in the risk of malignancy associated with the use of this medication.

Healthcare providers should counsel patients on the necessity of maintaining an adequate intake of calcium and vitamin D, recommending at least 1000 mg of elemental calcium and 400 International Units of vitamin D per day.

Patients must be instructed to seek emergency medical assistance or go to the nearest hospital emergency room immediately if they develop any signs or symptoms indicative of a serious allergic reaction.

Additionally, healthcare providers should guide patients on the correct storage methods for both unopened and opened products. It is crucial to inform patients that the bottle should be discarded after 14 doses (2 mL fill) or 30 doses (3.7 mL fill), as the medication may not be delivered in the correct dosage after these limits, even if the bottle appears to contain remaining medication.

Storage and Handling

The product is supplied in bottles that must be stored unopened in a refrigerator at temperatures ranging from 2°C to 8°C (36°F to 46°F). It is essential to protect the product from freezing during storage. Once the bottle is in use, it should be kept at room temperature between 20°C to 25°C (68°F to 77°F) in an upright position. The 2 mL fill can be stored at room temperature for up to 30 days, while the 3.7 mL fill can be stored for up to 35 days. After administering 14 doses from the 2 mL fill or 30 doses from the 3.7 mL fill, the bottle should be discarded.

Additional Clinical Information

Periodic nasal examinations are recommended for patients prior to initiating treatment with calcitonin salmon nasal spray, as well as during therapy and whenever nasal symptoms arise. These examinations should include visualization of the nasal mucosa, turbinates, septum, and mucosal blood vessels. Additionally, clinicians may consider periodic assessments of urine sediment.

For patients with suspected hypersensitivity to calcitonin salmon, it is advisable to conduct skin testing prior to treatment using a dilute, sterile solution of a calcitonin salmon injectable product. Healthcare providers may refer patients requiring skin testing to an allergist, and a detailed skin testing protocol is available from the Customer Service department of Apotex Corp. at 1-800-706-5575.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Calcitonin Salmon as submitted by Apotex Corp.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)