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 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 USP 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 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 observed improvement 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 postmenopausal osteoporosis, the recommended dosage is also 100 USP 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 adequate intake of calcium and vitamin D throughout the course of treatment.

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.

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 reactions.

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 reported and warrant careful consideration. Serious hypersensitivity reactions, including fatal anaphylaxis, have been documented. 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. In clinical observations, a dose of 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 fully assess toxicity.

Drug Interactions

Concomitant administration of calcitonin salmon and lithium has been associated with a reduction in plasma lithium concentrations. This interaction is attributed to the increased urinary clearance of lithium induced by calcitonin salmon. Therefore, it is advisable to monitor lithium levels closely and consider adjusting the lithium dosage as necessary to maintain therapeutic efficacy.

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 from younger patients. However, other reported clinical experience has 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 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 administered 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 shown to decrease fetal birth weights in rabbits, no embryo or fetal toxicities related to calcitonin salmon were reported in rats receiving 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 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 the use of 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 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 calcitonin salmon at a dose of 1000 International Units subcutaneously may result in 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 other significant adverse effects. It is important to note that data regarding the toxicity associated with chronic high-dose administration of calcitonin salmon are currently insufficient, and further investigation is warranted to fully understand the implications of prolonged exposure to elevated doses.

In the event of an overdose, monitoring for symptoms and providing supportive care, including the administration of calcium if hypocalcemia is suspected, is recommended.

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 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. These findings suggest that synthetic 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, a dose approximately 39 times higher than 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. This information has been reported voluntarily by patients and healthcare professionals, as well as through surveillance programs. It is important for healthcare providers to inform patients of this potential risk when considering treatment options.

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 responsibly 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 patients with postmenopausal osteoporosis or Paget’s disease of bone to maintain an adequate intake of calcium and vitamin D, specifically advising them to consume at least 1000 mg of elemental calcium and 400 International Units of vitamin D daily.

Additionally, healthcare providers should advise patients to seek emergency medical assistance or go to the nearest hospital emergency room immediately if they experience any signs or symptoms indicative of a serious allergic reaction.

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

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)