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 Injection, USP, Synthetic is a synthetic polypeptide consisting of 32 amino acids arranged in the same linear sequence as calcitonin derived from salmon. This product is available as a sterile solution intended for subcutaneous or intramuscular injection. Each milliliter contains 200 International Units of calcitonin salmon. The inactive ingredients per milliliter include 2.25 mg of acetic acid, 5.0 mg of phenol, 2.0 mg of sodium acetate trihydrate, 7.5 mg of sodium chloride, and water for injection.

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 postmenopausal 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 International 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 International Units per kilogram of body weight, administered every 12 hours. If there is no observed improvement within 1 to 2 days, the dosage may be increased to 8 International 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 International Units per kilogram every 6 hours.

For the management of postmenopausal osteoporosis, the recommended dosage is also 100 International Units daily, with a strong 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 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, and injection site inflammation, also reported in about 10% of participants. Flushing of the face or hands was noted in 2% to 5% of subjects.

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; therefore, it is essential to ensure adequate intake of calcium and vitamin D during treatment. A meta-analysis of 21 clinical trials has 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 response to treatment.

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, necessitating the availability of parenteral calcium for treatment. Notably, a dose of 1000 International Units subcutaneously may induce nausea and vomiting, while doses of 32 International Units per kg per day for 1 to 2 days have shown no other adverse effects. However, data on chronic high-dose administration are insufficient to adequately assess toxicity.

Drug Interactions

Concomitant administration 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 used together. Therefore, it may be necessary to adjust the dosage of lithium to maintain therapeutic levels and ensure efficacy.

No information regarding other drug or laboratory test interactions has been provided.

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 a sufficient number of subjects aged 65 years and older to determine whether these elderly patients respond differently from younger subjects. However, other reported clinical experience has not identified any significant differences in responses between geriatric patients and their younger counterparts.

In general, dose selection for elderly 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 4 to 18 times the recommended parenteral human dose resulted in a decrease in fetal birth weights. However, 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 2% to 4% and 15% to 20%, respectively. Given the findings in animal studies, healthcare professionals should consider the potential risks when prescribing calcitonin salmon to pregnant patients. It is recommended that women of childbearing potential discuss the use of this medication with their healthcare provider to weigh the benefits and risks.

Lactation

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, calcitonin has been shown to inhibit lactation in animal studies involving rats.

When considering the use of calcitonin salmon injection in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication. Additionally, potential adverse effects on the breastfed infant from calcitonin salmon injection or from the underlying maternal condition should be taken into account.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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 overdose with calcitonin salmon injection, the pharmacologic actions indicate that hypocalcemic tetany may occur. This condition is characterized by muscle spasms and cramps due to low calcium levels in the blood.

To manage an overdose effectively, it is essential that provisions for parenteral administration of calcium are readily available. This intervention is critical in addressing potential hypocalcemia resulting from excessive dosing.

Administration of a dose of calcitonin salmon at 1000 International Units subcutaneously has been associated with the onset of nausea and vomiting. Healthcare professionals should monitor patients for these symptoms and provide appropriate supportive care.

Clinical observations indicate that doses of 32 International Units per kg per day for a duration of 1 to 2 days do not demonstrate any other adverse effects. However, caution should still be exercised, and patients should be closely monitored for any signs of overdose-related complications.

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, neoplasms associated with synthetic calcitonin salmon were not observed in mice after two years of dosing.

In male Fisher 344 rats and female Sprague Dawley rats, an increase in the incidence of pituitary adenomas was noted 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 significantly 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 resulted in an increased incidence of pituitary adenomas after two years of dosing (1.7 International Units/kg/day) is approximately one-sixth of the maximum recommended subcutaneous dose in humans (100 International Units/day), based on body surface area conversion between rats and humans. These findings suggest that calcitonin salmon may reduce the latency period for the development of non-functioning pituitary adenomas.

No evidence of carcinogenicity 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, which is approximately 39 times the maximum recommended subcutaneous dose in humans (100 International Units/day) based on body surface area conversion.

Synthetic calcitonin salmon was tested for mutagenicity and was 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 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 calcitonin salmon. It is essential to emphasize the importance of disposing of needles safely to prevent injury or contamination.

Patients should be informed about the potential increase in the risk of malignancy associated with the use of calcitonin salmon. This information is crucial for patients to make informed decisions regarding their treatment.

For patients diagnosed with postmenopausal 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 1000 mg of elemental calcium and 400 International Units of vitamin D per day to support their bone health.

Additionally, patients must be instructed to seek emergency medical assistance or visit the nearest hospital emergency room 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 imperative to avoid freezing the product to maintain its integrity and efficacy. Proper storage conditions are essential for ensuring the product remains effective throughout its shelf life.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)