Calcitonin salmon

Description

Calcitonin, USP 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 that found in salmon-derived calcitonin. 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, USP (2.25 mg), phenol, USP (5.0 mg), sodium acetate trihydrate, USP (2.0 mg), sodium chloride, USP (7.5 mg), and water for injection, USP. 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 provided 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. 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 specific 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, therapy should commence with a dosage of 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 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 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 agent.

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

Most common adverse reactions observed in clinical trials include nausea with or without vomiting (10%) and injection site inflammation (10%). Flushing of the face or hands was reported in 2% to 5% of participants.

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. Hypocalcemia has also been reported; therefore, ensuring adequate intake of calcium and vitamin D is advised. A meta-analysis encompassing 21 clinical trials indicates an increased risk of overall malignancies in patients treated with calcitonin-salmon. Additionally, 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, necessitating the availability of parenteral calcium for treatment. 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 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 pharmacokinetic interaction characterized by a reduction in plasma lithium concentrations. This effect is attributed to an increase in the urinary clearance of lithium when these two agents are used together. Consequently, it may be necessary to adjust the dosage of lithium to maintain therapeutic levels and ensure efficacy. Monitoring of lithium plasma levels is recommended to guide appropriate dosage adjustments.

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 this population responds differently compared to younger subjects. However, other reported clinical experiences have not identified significant differences in responses between elderly patients and their younger counterparts.

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 2 to 4% and 15 to 20%, respectively. Given the findings in animal studies, healthcare professionals should weigh the potential risks and benefits of calcitonin-salmon use in pregnant patients. Caution is advised when prescribing this medication to women of childbearing potential.

Lactation

There are no studies available regarding the use of calcitonin-salmon injection in nursing mothers, which limits the ability to assess the associated risk of infant exposure through 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 lactating mother.

Renal Impairment

There is no specific information 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, the pharmacologic actions indicate a potential risk for 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 1000 International Units subcutaneously may lead to gastrointestinal symptoms, specifically nausea and vomiting. However, doses of 32 International Units per kg per day for a duration of 1 to 2 days have not demonstrated any significant adverse effects. It is important to note that data regarding the toxicity of chronic high-dose administration remain insufficient, necessitating caution and further investigation in such scenarios.

Healthcare professionals should monitor patients closely for symptoms of overdose and be prepared to initiate appropriate management strategies, including the administration of calcium as needed.

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 the only significant neoplastic finding after one year of subcutaneous dosing. In male Sprague Dawley rats dosed for one and two years, a similar increase was noted. 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 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. These findings suggest that calcitonin-salmon may reduce the latency period for the development of non-functioning pituitary adenomas.

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, 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 found to be negative 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 administering calcitonin-salmon injection. It is essential to emphasize the importance of proper disposal of needles to ensure safety and prevent injury.

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 with patients, allowing them 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 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°C to 8°C (36°F to 46°F). It is essential to maintain these temperature conditions to ensure the integrity and efficacy of the product. Proper handling and storage in a refrigerator are crucial for preserving the quality of the product.

Additional Clinical Information

Periodic examinations of urine sediment should be considered for patients undergoing treatment. For those with suspected hypersensitivity to calcitonin-salmon, clinicians are advised to consider skin testing prior to treatment. This testing should utilize a dilute, sterile solution of calcitonin-salmon injection, and healthcare providers may refer patients to an allergist for this procedure. A detailed skin testing protocol is available from the Dr. Reddy’s Laboratories Inc. Medical Service team.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Calcitonin Salmon as submitted by Dr. Reddy's Laboratories, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)