Calcitonin salmon

Description

Calcitonin is a polypeptide hormone produced by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland in 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 formulation is supplied as a sterile solution intended for subcutaneous or intramuscular injection, with each milliliter containing 200 International Units of calcitonin-salmon.

The inactive ingredients per milliliter include acetic acid (2.25 mg), phenol (5.0 mg), sodium acetate trihydrate (2.0 mg), sodium chloride (7.5 mg), and water for injection. The potency of Calcitonin Salmon Injection is expressed in International Units, determined through bioassay in comparison with the International Reference Preparation of calcitonin-salmon for Bioassay, as distributed by the National Institute for Biological Standards and Control, Holly Hill, London.

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 and for the treatment of postmenopausal osteoporosis in cases where alternative treatments are not appropriate. It is important to note that the efficacy of this drug in reducing fractures in postmenopausal osteoporosis has not been demonstrated.

Limitations of use include the need for periodic re-evaluation of the necessity for continued therapy, particularly due to a possible association between malignancy and the use of calcitonin-salmon.

No specific teratogenic or nonteratogenic effects have been identified.

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 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 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 and warrant careful consideration. Notably, serious hypersensitivity reactions, including reports of fatal anaphylaxis, 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; therefore, ensuring adequate intake of calcium and vitamin D is essential for patients undergoing treatment. 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.

Other important notes include the possibility of 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; thus, provisions for parenteral administration of calcium should be readily available for the treatment of such events. A dose of calcitonin-salmon at 1000 International Units subcutaneously may lead to nausea and vomiting, while doses of 32 International Units per kg per day for 1 to 2 days have demonstrated no other adverse effects. However, data on chronic high-dose administration are insufficient to assess toxicity comprehensively.

Drug Interactions

Concomitant administration of calcitonin-salmon and lithium may result in a pharmacokinetic interaction characterized by a reduction in plasma lithium concentrations. This effect is attributed to an increase in the urinary clearance of lithium when both agents are used together. Consequently, it may be necessary to adjust the dosage of lithium to maintain therapeutic levels and ensure effective management of the patient's condition. Monitoring of lithium plasma levels is recommended to guide any necessary dosage modifications.

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 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 recommended 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 advised 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 2-4% and 15-20%, respectively. While calcitonin-salmon has been associated with decreased fetal birth weights in rabbits, no embryo/fetal toxicities related to calcitonin-salmon were reported in rats at maternal subcutaneous daily doses of up to 80 International Units/kg/day from gestation days 6 to 15.

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

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 in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for calcitonin-salmon injection. 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 this patient population.

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 injection, healthcare professionals should be aware of the potential pharmacologic actions that may lead to hypocalcemic tetany. It is essential to have provisions for the parenteral administration of calcium readily available to manage this condition effectively.

Administration of a dose of 1000 International Units of calcitonin-salmon subcutaneously may result in gastrointestinal symptoms, specifically nausea and vomiting. However, clinical data indicate that doses of 32 International Units per kg per day for a duration of 1 to 2 days do not demonstrate any other significant adverse effects. It is important to note that there is insufficient data regarding the toxicity associated with chronic high-dose administration of calcitonin-salmon, which necessitates caution and further investigation in such scenarios.

In summary, appropriate measures should be taken to monitor and manage symptoms of overdosage, particularly the availability of calcium for hypocalcemic tetany, while being vigilant about the potential for nausea and vomiting at higher doses.

Nonclinical Toxicology

The evaluation of synthetic calcitonin-salmon in nonclinical studies has provided insights into its potential effects on carcinogenicity, mutagenicity, and fertility.

Carcinogenesis, Mutagenesis, Impairment of Fertility In long-term studies, an increased incidence of pituitary adenomas was observed in rats following one and two years of subcutaneous administration of synthetic calcitonin-salmon. This finding was particularly noted 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 attribute a treatment-related effect distinct from the natural background incidence. The lowest dose associated with an increased incidence of pituitary adenomas in male Sprague Dawley rats after two years was approximately 1.7 International Units/kg/day, which is about one-sixth of the maximum recommended subcutaneous dose in humans (100 International Units/day) based on body surface area conversion. These findings suggest that synthetic calcitonin-salmon may reduce the latency period for the development of non-functioning pituitary adenomas. Conversely, no carcinogenic 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, a dose approximately 39 times higher than the maximum recommended subcutaneous dose in humans.

Synthetic calcitonin-salmon has been 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 injection. 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 this medication. It is crucial for healthcare providers to discuss this risk openly, allowing 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, healthcare providers must instruct patients 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 container that is not made with natural rubber latex. It should be stored in a refrigerator at a temperature range of 2° to 8°C (36° to 46°F). Care should be taken to avoid freezing the product, as this may compromise its integrity.

Additional Clinical Information

Periodic examinations of urine sediment should be considered for patients undergoing treatment. There is no additional information available regarding abuse potential, 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 Fresenius Kabi USA, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)