Calcitonin salmon

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 women when alternative treatments are not suitable; however, fracture reduction efficacy has not been demonstrated.

Limitations of Use

Due to the possible association between malignancy and calcitonin-salmon use, the need for continued therapy should be re-evaluated on a periodic basis.

Special Population

For the nasal formulation, it is specifically indicated for the treatment of postmenopausal osteoporosis in women greater than 5 years postmenopause when alternative treatments are not suitable, with the same note regarding fracture reduction efficacy.

Dosage and Administration

For the treatment of symptomatic Paget’s disease of bone, the recommended dosage is 100 USP Units (or International Units) administered daily. It is essential to ensure adequate intake of calcium and vitamin D during treatment.

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

For postmenopausal osteoporosis, the recommended dosage is also 100 USP Units (or International Units) daily, with the same requirement for adequate calcium and vitamin D intake.

For intranasal administration, one spray (200 USP Units or International Units) should be administered per day, alternating nostrils daily. Prior to the first use, the bottle should be allowed to reach room temperature and the pump must be primed. Adequate calcium and vitamin D intake should also be ensured during this treatment.

Contraindications

Use of calcitonin salmon is contraindicated in individuals with hypersensitivity to calcitonin salmon or any of its excipients. This includes all formulations, such as injection, solution, and metered spray.

Warnings and Precautions

Serious hypersensitivity reactions, including reports of fatal anaphylaxis, have been reported. It is recommended to consider skin testing prior to treatment in patients with suspected hypersensitivity to calcitonin salmon.

Hypocalcemia

Hypocalcemia has been reported in patients receiving calcitonin salmon. It is essential to ensure adequate intake of calcium and vitamin D to mitigate this risk.

Malignancy Risk

A meta-analysis of 21 clinical trials suggests an increased risk of overall malignancies in patients treated with calcitonin salmon. This potential risk should be carefully considered when prescribing this medication.

Antibody Development

Circulating antibodies to calcitonin salmon may develop during treatment, which could lead to a loss of response to the medication. Monitoring for this development is advised.

Nasal Adverse Reactions

For patients using the nasal spray formulation, nasal adverse reactions, including severe ulceration, can occur. Periodic nasal examinations are recommended to monitor for these potential complications.

Side Effects

Patients receiving calcitonin salmon may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common Adverse Reactions

• Nausea with or without vomiting: Occurs in approximately 10% of patients, particularly evident at the initiation of treatment and may decrease with continued administration.

• Injection site inflammation: Reported in about 10% of patients.

• Flushing of the face or hands: Observed in 2% to 5% of patients.

• Other reactions: Additional adverse reactions may include rhinitis, epistaxis, back pain, arthralgia, headache, nocturia, feverish sensation, pain in the eyes, poor appetite, abdominal pain, pedal edema, and a salty taste.

Serious Adverse Reactions

• Serious hypersensitivity reactions: Including reports of fatal anaphylaxis. Skin testing is recommended prior to treatment in patients with suspected hypersensitivity to calcitonin salmon.

• Hypocalcemia: Patients should ensure adequate intake of calcium and vitamin D, as hypocalcemia has been reported.

• Malignancy: A meta-analysis of 21 clinical trials indicates an increased risk of overall malignancies in patients treated with calcitonin salmon compared to those receiving placebo.

• Circulating antibodies: Development of antibodies to calcitonin salmon may occur, potentially leading to a loss of response to treatment.

• Nasal adverse reactions: In patients using the nasal spray formulation, severe ulceration and other nasal symptoms have been reported, necessitating periodic nasal examinations.

Important Notes

• Patients with hypersensitivity to calcitonin salmon or any of its excipients should not use this medication.

• The pharmacologic actions of calcitonin salmon suggest that hypocalcemic tetany could occur in cases of overdose; therefore, provisions for parenteral administration of calcium should be available.

• A dose of calcitonin salmon 1,000 International Units subcutaneously may produce nausea and vomiting, while doses of 32 International Units per kg per day for 1 to 2 days have shown no other adverse effects. Data on chronic high-dose administration are insufficient to assess toxicity.

Drug Interactions

Concomitant use of calcitonin salmon, available in injection, solution, and metered spray forms, with lithium may lead to a reduction in plasma lithium concentrations. This interaction is attributed to increased urinary clearance of lithium, which may necessitate an adjustment in the lithium dosage to maintain therapeutic levels.

No additional drug or laboratory test interactions have been reported for calcitonin salmon.

Pediatric Use

Safety and effectiveness of Calcitonin Salmon and Miacalcin in pediatric patients have not been established. This includes all formulations, such as injection, solution, and metered spray. Due to the lack of data, caution is advised when considering these medications for use in children and adolescents.

Geriatric Use

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

In general, dose selection for elderly patients should be approached with caution, typically starting at the low end of the dosing range. This recommendation reflects the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies in this population.

Notably, in a multi-centered, double-blind, randomized clinical study of calcitonin salmon nasal spray, the incidence of nasal adverse reactions, such as rhinitis, irritation, erythema, and excoriation, was higher in patients aged 65 and older, particularly among those over 75 years of age. While no definitive differences in overall responses have been established, the potential for greater sensitivity in some older individuals cannot be ruled out. Therefore, careful monitoring and consideration of individual patient factors are advised when treating geriatric patients with calcitonin salmon.

Pregnancy

There are no studies with calcitonin salmon injection or Miacalcin in pregnant patients to inform a drug-associated risk for birth defects or miscarriage. In animal reproduction studies, subcutaneous administration of calcitonin salmon to pregnant rabbits during organogenesis at doses 4 to 18 times the recommended parenteral human dose resulted in decreased fetal birth weights. However, no adverse developmental outcomes were observed in rats administered subcutaneous calcitonin salmon at 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. While calcitonin salmon has been shown to decrease fetal birth weights in rabbits, no embryo/fetal toxicities related to calcitonin salmon were reported from maternal subcutaneous daily doses in rats up to 80 International Units/kg/day from gestation days 6 to 15.

Calcitonin salmon nasal solution is not indicated for use in females of reproductive potential, and there are no data regarding its use in pregnant women. Similar findings regarding decreased fetal birth weights were noted in rabbits when administered calcitonin salmon at doses significantly higher than those recommended for human use. No embryo/fetal toxicities were reported in rats for the nasal formulation as well.

Given the lack of human studies and the observed effects in animal models, healthcare providers should exercise caution when considering the use of calcitonin salmon or Miacalcin in pregnant patients.

Lactation

There are no studies available regarding the excretion of calcitonin salmon in breast milk or its effects on breastfed infants. The potential for calcitonin salmon to be present in human milk has not been established, and there is no information on its impact on milk production.

It is important to note that calcitonin has been shown to inhibit lactation in animal studies (specifically in rats). Therefore, caution should be exercised when administering calcitonin salmon to lactating mothers. The developmental and health benefits of breastfeeding should be carefully weighed against the mother's clinical need for calcitonin salmon and any potential adverse effects on the breastfed infant stemming from the medication or the underlying maternal condition.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available labeling for Calcitonin Salmon and Miacalcin. The provided information does not include any recommendations regarding dosage adjustments, special monitoring, or safety considerations for individuals with reduced kidney function. Consequently, healthcare professionals should exercise caution when considering the use of these medications in patients with renal impairment, as the lack of specific guidance necessitates careful clinical judgment. Regular monitoring of renal function may be prudent in these cases, although no explicit thresholds or recommendations are outlined in the current labeling.

Hepatic Impairment

Patients with hepatic impairment have no specific dosage adjustments, special monitoring requirements, or precautions outlined for the use of Calcitonin Salmon or Miacalcin in any of its forms, including injection, solution, and metered spray. The available data does not provide guidance on the management of these patients, indicating that further clinical judgment may be necessary when considering treatment options.

Overdosage

In cases of overdose with calcitonin salmon, hypocalcemic tetany may occur, necessitating the availability of parenteral calcium for treatment. Symptoms of overdose may include nausea and vomiting, particularly following a subcutaneous dose of 1,000 International Units.

Doses of 32 International Units per kg per day for 1 to 2 days have been shown to produce no significant adverse effects. However, data regarding the toxicity of chronic high-dose administration remain insufficient.

For patients receiving calcitonin salmon nasal spray, single doses up to 1,600 International Units and daily doses of up to 800 International Units for 3 days have been studied without serious adverse effects. Chronic administration of doses up to 600 International Units per day has also been evaluated without significant toxicity.

Monitoring for symptoms of hypocalcemia and ensuring the availability of calcium for parenteral administration are critical components of managing an overdose situation.

Nonclinical Toxicology

Teratogenic Effects

No information regarding teratogenic effects is available.

Non-Teratogenic Effects

The incidence of pituitary adenomas was increased in rats following one and two years of subcutaneous exposure to synthetic calcitonin salmon. The significance of this finding to humans remains uncertain, as pituitary adenomas are common in aging rats. These adenomas did not progress to metastatic tumors, and no other clear treatment-related neoplasms were observed. Additionally, synthetic calcitonin salmon-related neoplasms were not detected in mice after two years of dosing.

The only notable neoplastic finding in rats treated with calcitonin salmon was an increase in the 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 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 exhibited 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity 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, 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 tested negative for mutagenicity in assays using Salmonella typhimurium (five strains) and Escherichia coli (two strains), both with and without rat liver metabolic activation. It was also not clastogenic in a chromosome aberration test in Chinese Hamster V79 cells, and no evidence of clastogenicity was found in the in vivo mouse micronucleus test.

Effects of calcitonin salmon on fertility have not been assessed in animals.

Storage and Handling

Calcitonin Salmon is supplied in various forms, including Injection, Solution, and Metered Spray.

Storage Conditions:

• All formulations should be stored in a refrigerator between 2°C to 8°C (36°F to 46°F).

• It is essential to protect the product from freezing.

• For the Metered Spray, the unopened bottle should be kept in the refrigerator, while the bottle in use can be stored at room temperature between 20°C to 25°C (68°F to 77°F) in an upright position. The in-use bottle should be discarded after 30 doses (for 3.7 mL fill) or 14 doses (for 2 mL fill).

Handling Requirements:

• The container closure is not made with natural rubber latex, ensuring compatibility for individuals with latex sensitivities.

• All products are sterile and nonpyrogenic, maintaining safety and efficacy during use.