Calcitonin salmon

Description

Calcitonin salmon injection USP, synthetic, is a synthetic polypeptide composed of 32 amino acids arranged in the same linear sequence as calcitonin derived from salmon. It appears as a white to off-white powder and is soluble in water and 1% aqueous acetic acid. The chemical name is L-cysteinyl-L-seryl-L-asparginyl-L-leucyl-L-seryl-L-threonyl-L-cysteinyl-L-valyl-L-leucyl-glycyl-L-lysyl-L-leucyl-L-seryl-L-glutaminyl-L-alpha-glutamyl-L-leucyl-L-histidyl-L-lysyl-L-leucyl-L-glutaminyl-L-threonyl-L-tyrosyl-L-prolyl-L-arginyl-L-threonyl-L-asparginyl-L-threonyl-glycyl-L-seryl-glycyl-L-threonyl-L-prolinamide (1->7)-disulfide, with a molecular formula of C145H240N44O48S2 and a molecular weight of 3432 Daltons.

Calcitonin salmon injection, USP, synthetic, is available in a sterile, clear, colorless solution at a concentration of 400 USP Units per 2 mL (200 USP Units/mL), packaged in individual 2 mL multiple-dose clear glass vials for subcutaneous or intramuscular injection. Each 1 mL of the solution contains 0.03333 mg of calcitonin salmon, equivalent to 200 USP calcitonin salmon units. Inactive ingredients include acetic acid (2.25 mg), phenol (5.00 mg), sodium acetate trihydrate (2.00 mg), sodium chloride (7.50 mg), and water for injection, USP, q.s. to 1.00 mL.

Uses and Indications

This drug is indicated for the treatment of symptomatic Paget’s disease of bone when alternative treatments are not suitable. It is also indicated for the treatment of hypercalcemia. Additionally, this drug is indicated for the treatment of post-menopausal osteoporosis in cases where alternative treatments are not suitable; however, the efficacy for fracture reduction has not been demonstrated.

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

Dosage and Administration

For the treatment of symptomatic Paget’s disease of bone, the recommended dosage is 100 USP Units administered daily. It is essential to ensure that patients receive adequate calcium and vitamin D intake during the course of treatment.

In cases of hypercalcemia, the initial dosage should be 4 USP Units per kilogram of body weight, administered every 12 hours. If there is no improvement observed within 1 to 2 days, the dosage may be increased to 8 USP Units per kilogram every 12 hours. Should there still be no improvement after an additional 2 days, the dosage can be further escalated to 8 USP Units per kilogram every 6 hours.

For the management of post-menopausal osteoporosis, the recommended dosage is also 100 USP Units daily, with an emphasis on ensuring adequate calcium and vitamin D intake.

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 instances of fatal anaphylaxis, have been documented in patients receiving calcitonin salmon. It is advisable to consider conducting skin testing prior to initiating treatment in individuals with a suspected hypersensitivity to this agent.

Patients should be monitored for hypocalcemia, which has been reported in some cases. To mitigate this risk, it is essential to ensure that patients have an adequate intake of calcium and vitamin D.

Additionally, a meta-analysis encompassing 21 clinical trials has indicated a potential increase in the risk of overall malignancies among patients treated with calcitonin salmon. Healthcare professionals should remain vigilant regarding this risk and consider appropriate patient counseling and monitoring.

Furthermore, the development of circulating antibodies to calcitonin salmon may occur, potentially leading to a diminished therapeutic response. Regular assessment of treatment efficacy is recommended to identify any loss of response that may necessitate a reevaluation of the treatment regimen.

Side Effects

Patients receiving calcitonin salmon may experience a range of adverse reactions, which can be categorized into common and serious events.

Common adverse reactions observed in clinical trials include nausea with or without vomiting, which occurred in approximately 10% of patients. Injection site inflammation was also reported in 10% of participants, while flushing of the face or hands was noted in 2% to 5% of cases.

Serious adverse reactions have been documented, including serious hypersensitivity reactions, with reports of fatal anaphylaxis. It is recommended that skin testing be considered 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. A meta-analysis encompassing 21 clinical trials indicated 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 therapeutic response.

Other important considerations include the potential for hypersensitivity to calcitonin salmon or any of its excipients. The pharmacologic actions of calcitonin salmon injection suggest that hypocalcemic tetany could occur in cases of overdose; therefore, provisions for the parenteral administration of calcium should be readily available. Notably, a dose of 1,000 International Units subcutaneously may induce nausea and vomiting, while doses of 32 International Units per kg per day for 1 to 2 days have not demonstrated other adverse effects. However, data on the toxicity of chronic high-dose administration remain insufficient.

Drug Interactions

Concomitant use of calcitonin salmon and lithium may result in a pharmacokinetic interaction characterized by a reduction in plasma lithium concentrations. This effect is attributed to 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 and ensure efficacy.

No additional drug or laboratory test interactions have been reported.

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

Clinical studies of calcitonin salmon injection did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger patients.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Careful monitoring of these patients is recommended to ensure safety and efficacy.

Pregnancy

There are no studies with calcitonin salmon injection in pregnant women to inform a drug-associated risk for birth defects or miscarriage. In an animal reproduction study, subcutaneous administration of calcitonin salmon to pregnant rabbits during organogenesis at doses ranging from 4 to 18 times the recommended parenteral human dose resulted in a decrease in fetal birth weights. Conversely, no adverse developmental outcomes were observed in rats receiving subcutaneous calcitonin salmon at doses up to 9 times the recommended human parenteral dose based on body surface area.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is between 2% to 4% and 15% to 20%, respectively. While calcitonin salmon has been associated with decreased fetal birth weights in rabbits, no embryo/fetal toxicities related to the drug were reported in rats administered daily subcutaneous doses of up to 80 International Units/kg/day from gestation days 6 to 15.

Given the lack of human data and the findings from animal studies, healthcare professionals should weigh the potential risks and benefits when considering the use of calcitonin salmon in pregnant patients.

Lactation

There are no studies available regarding the use of calcitonin salmon injection in nursing mothers to inform a drug-associated risk for excretion in breast milk. The potential for excretion of calcitonin salmon in breast milk has not been established. Therefore, caution should be exercised when administering calcitonin salmon to a nursing mother.

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, healthcare professionals should be vigilant for the potential occurrence of hypocalcemic tetany. It is essential that provisions for the parenteral administration of calcium are readily available to manage this condition effectively.

Administration of calcitonin salmon at a dose of 1,000 International Units via subcutaneous injection may lead to gastrointestinal disturbances, specifically nausea and vomiting. Therefore, monitoring for these symptoms is advised following administration.

Clinical observations indicate that doses of 32 International Units per kg per day for a duration of 1 to 2 days have not been associated with any significant adverse effects. However, continuous assessment of the patient’s condition is recommended to ensure safety and prompt intervention if necessary.

Nonclinical Toxicology

Carcinogenicity studies indicated an increased incidence of pituitary adenomas 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, no neoplasms associated with synthetic calcitonin salmon were observed in mice after two years of dosing.

In rats, the primary neoplastic finding was an elevated incidence of pituitary adenomas in male Fisher 344 rats and female Sprague Dawley rats after one year of dosing, 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 associated with an increased incidence of pituitary adenomas in male Sprague Dawley rats after two years of dosing was 1.7 International Units/kg/day, which is approximately one-sixth of the maximum recommended subcutaneous dose in humans (100 International Units/day) when adjusted for body surface area.

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, a dose approximately 39 times higher than the maximum recommended subcutaneous dose in humans.

Mutagenicity testing revealed that synthetic calcitonin salmon was negative for mutagenic effects in assays using Salmonella typhimurium (five strains) and Escherichia coli (two strains), both with and without rat liver metabolic activation. Additionally, it was not found to be 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 indicated a potential increase in the risk of malignancy associated with the use of the product. Healthcare professionals are advised to inform patients of this risk, as detailed in the Warnings and Precautions section (5.3).

Patient Counseling

Healthcare providers should instruct patients and caregivers on the proper sterile injection technique for administering calcitonin salmon injection. It is essential to emphasize the importance of disposing of needles safely and in accordance with local regulations to prevent any potential harm.

Patients should be informed about the potential increase in the risk of malignancy associated with the use of this medication. It is crucial for healthcare providers to discuss this risk openly, ensuring that patients understand the implications.

For patients diagnosed with post-menopausal osteoporosis or Paget’s disease of bone, healthcare providers should advise them to maintain an adequate intake of calcium and vitamin D. Specifically, patients should aim for at least 1,000 mg of elemental calcium and 400 International Units of vitamin D per day to support their bone health.

Additionally, healthcare providers must instruct patients to seek emergency medical assistance immediately if they experience any signs or symptoms indicative of a serious allergic reaction. Prompt action in such cases is vital for patient safety.

Storage and Handling

The product is supplied in a refrigerated state and must be stored at temperatures between 2° to 8°C (36° to 46°F). It is essential to protect the product from freezing to maintain its integrity and efficacy. Proper handling and storage conditions are critical to ensure the product remains within the specified temperature range.

Additional Clinical Information

Periodic examinations of urine sediment should be considered for patients undergoing treatment. There is no additional information available regarding abuse, route, method, frequency of administration, patient counseling, or postmarketing experience.

FDA Insert (PDF)

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

View full prescribing information (PDF)