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 Nasal Solution is a synthetic polypeptide consisting of 32 amino acids arranged in the same linear sequence as calcitonin derived from salmon. This formulation is supplied in a 3.7 mL glass bottle, designed for nasal administration, providing sufficient medication for 30 doses.

The active ingredient in this solution is calcitonin-salmon, with a concentration of 2200 International Units per mL, which corresponds to 200 International Units per 0.09 mL actuation. Inactive ingredients include sodium chloride, chlorobutanol, hydrochloric acid (added as necessary to adjust pH), purified water, and nitrogen. The potency of Calcitonin Salmon Nasal Solution is expressed in International Units, determined through bioassay in comparison with the International Reference Preparation of calcitonin-salmon, as distributed by the National Institute of Biological Standards and Control, Holly Hill, London.

Uses and Indications

Calcitonin Salmon Nasal Solution is indicated for the treatment of postmenopausal osteoporosis in women who are more than 5 years postmenopause when alternative treatments are not suitable.

Limitations of Use: The efficacy of Calcitonin Salmon Nasal Solution in reducing fractures has not been demonstrated.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

For intranasal administration, the recommended dosage is one spray, delivering 200 International Units, once daily. Patients should alternate nostrils with each administration to ensure even distribution and effectiveness.

Before the initial use, it is essential to allow the bottle to reach room temperature and to prime the pump to ensure proper functioning. Additionally, healthcare professionals should advise patients to maintain adequate intake of calcium and vitamin D to support overall treatment efficacy.

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 anaphylactic shock, have been reported in patients receiving calcitonin-salmon. It is advisable to consider skin testing prior to initiating treatment in individuals with suspected hypersensitivity to this agent (5.1).

Patients should be monitored for hypocalcemia, which has been documented in some cases. It is essential to ensure that patients have an adequate intake of calcium and vitamin D to mitigate this risk (5.2).

Nasal adverse reactions, including severe ulceration, may occur with the use of calcitonin-salmon. To monitor for these potential complications, periodic nasal examinations are recommended (5.3).

There is an observed association between calcitonin-salmon treatment and an increased risk of overall malignancies, as indicated by a meta-analysis of 21 clinical trials. Healthcare professionals should remain vigilant regarding this potential risk in treated patients (5.4, 6.1).

Additionally, circulating antibodies to calcitonin-salmon may develop in some patients, which could lead to a diminished response to treatment. Monitoring for this development is advised to ensure continued efficacy of therapy (5.5).

Side Effects

Patients receiving calcitonin-salmon may experience a range of adverse reactions, which can be categorized into common and serious events.

The most common adverse reactions reported include rhinitis, epistaxis and other nasal symptoms, back pain, arthralgia, and headache. These reactions are generally mild and may not require medical intervention.

Serious adverse reactions have also been observed. Notably, serious hypersensitivity reactions, including anaphylactic shock, have been reported. It is advisable to consider skin testing prior to treatment in patients with a suspected hypersensitivity to calcitonin-salmon. Additionally, hypocalcemia has been documented; therefore, ensuring adequate intake of calcium and vitamin D is recommended for patients undergoing treatment.

Nasal adverse reactions, including severe ulceration, can occur, necessitating periodic nasal examinations to monitor for potential complications. Furthermore, a meta-analysis of 21 clinical trials indicates an increased risk of overall malignancies in patients treated with calcitonin-salmon. Patients may also develop circulating antibodies to calcitonin-salmon, which could lead to a loss of therapeutic response.

Patients should be monitored for hypersensitivity to calcitonin-salmon or any of its excipients, as this may also contribute to adverse reactions.

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 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

In a multi-centered, double-blind, randomized clinical study of calcitonin-salmon nasal solution, a total of 467 patients aged 65 to 74 years and 196 patients aged 75 years and older were evaluated alongside 279 patients younger than 65 years. The findings indicated that elderly patients, particularly those aged 75 years and older, experienced a higher incidence of nasal adverse reactions, including rhinitis, irritation, erythema, and excoriation, compared to their younger counterparts.

While other clinical experiences have not demonstrated significant differences in responses between elderly and younger patients, it is important to consider that some older individuals may exhibit greater sensitivity to treatment. Therefore, healthcare providers should exercise caution when prescribing this medication to geriatric patients, particularly those aged 75 years and older. Monitoring for adverse reactions is recommended, and dose adjustments may be necessary based on individual patient response and tolerance.

Pregnancy

Calcitonin Salmon Nasal Solution is not indicated for use in females of reproductive potential. There are no available data regarding the use of Calcitonin Salmon Nasal Solution in pregnant women. Animal reproduction studies have demonstrated that 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 administered subcutaneous calcitonin-salmon at doses up to 9 times the recommended human parenteral dose based on body surface area.

It is important to note that calcitonin-salmon has been associated with decreased fetal birth weights in rabbits when administered via subcutaneous injection at doses 4 to 18 times the parenteral dose (54 International Units/m²) and 70 to 278 times the intranasal dose recommended for human use based on body surface area. However, no embryo/fetal toxicities related to Calcitonin Salmon Nasal Solution were reported from maternal subcutaneous daily doses in rats 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 exercise caution when considering the use of Calcitonin Salmon Nasal Solution in pregnant patients.

Lactation

Calcitonin Salmon Nasal Solution is not indicated for use in females of reproductive potential. 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, it is noted that calcitonin has been shown to inhibit lactation in animal studies involving rats. Therefore, caution is advised when considering the use of this medication in lactating mothers.

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 Nasal Solution, the pharmacologic actions of the medication indicate that hypocalcemic tetany may occur. It is essential for healthcare professionals to ensure that provisions for the parenteral administration of calcium are readily available for the treatment of such an overdose.

Clinical studies have demonstrated that single doses of Calcitonin Salmon Nasal Solution up to 1600 International Units, as well as daily doses of up to 800 International Units for three consecutive days, and chronic administration of doses up to 600 International Units per day, have been evaluated without resulting in serious adverse effects. However, vigilance is warranted, and appropriate management strategies should be in place to address any potential symptoms arising from an overdose.

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 subcutaneous dosing with synthetic calcitonin-salmon. 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 was 1.7 International Units/kg/day, which is approximately twice the maximum recommended intranasal dose in humans (200 International Units/day) when adjusted for body surface area and accounting for a 20-fold conversion factor to reflect decreased clinical exposure via the intranasal route. These findings suggest that synthetic 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. This dose is approximately 390 times the maximum recommended intranasal dose in humans (200 International Units), based on body surface area scaling and a 20-fold conversion factor for low clinical exposure via the intranasal route.

Synthetic calcitonin-salmon was tested for mutagenicity and 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 identified several adverse events associated with the use of Calcitonin Salmon Nasal Solution, reported voluntarily or through surveillance programs.

Allergic reactions have been documented, with some cases being serious and potentially life-threatening. Symptoms of an allergic reaction may include difficulty breathing, facial or throat swelling, rapid heartbeat, chest pain, and dizziness or faintness. Immediate medical attention is advised if these symptoms occur.

Additionally, Calcitonin Salmon Nasal Solution may lead to decreased calcium levels in the blood. Patients with pre-existing low blood calcium may experience exacerbation of this condition during treatment. While many individuals with low blood calcium do not exhibit symptoms, some may experience numbness or tingling in the extremities or around the mouth, necessitating prompt consultation with a healthcare provider.

Nasal irritation has also been reported, particularly in individuals over 65 years of age. Symptoms may include crusting, dryness, redness, swelling, nasal sores, or nosebleeds. Healthcare providers may consider pausing treatment until these symptoms resolve.

Furthermore, there is an observed increased risk of cancer among individuals using calcitonin-salmon, the active ingredient in Calcitonin Salmon Nasal Solution. Regular urine testing by healthcare providers is recommended during the course of treatment to monitor for potential complications.

Patient Counseling

Healthcare providers should instruct patients on the proper assembly and priming of the pump for Calcitonin Salmon Nasal Solution, as well as the correct method for nasal administration. Although written instructions accompany each bottle, it is essential that healthcare providers demonstrate these procedures to ensure patient understanding.

Patients should be advised to notify their healthcare provider if they experience significant nasal irritation during use. It is important to inform patients about the potential increase in the risk of malignancy associated with this medication. Additionally, healthcare providers should emphasize the necessity of maintaining adequate intake of calcium (at least 1000 mg of elemental calcium per day) and vitamin D (at least 400 International Units per day) to support overall health while using this treatment.

Patients must be instructed to seek emergency medical assistance or visit the nearest hospital emergency room immediately if they exhibit any signs or symptoms of a serious allergic reaction. Proper storage instructions for both unopened and opened products should be communicated clearly to patients. They should also be informed that the bottle should be discarded after 30 doses, as the accuracy of each spray may be compromised beyond this point, even if the bottle is not completely empty.

It is crucial for patients to use Calcitonin Salmon Nasal Solution exactly as directed by their healthcare provider and to refrain from using the solution until they have received proper instruction and demonstrated understanding of its use. Patients should be encouraged to report any discomfort or irritation in the nose that occurs during treatment.

Healthcare providers should prescribe calcium and vitamin D supplements to help prevent low calcium levels in the blood while patients are using Calcitonin Salmon Nasal Solution, and patients should take these supplements as directed. Patients should also keep track of the number of doses used from their bottle.

In the event of an overdose, patients must be advised to contact their healthcare provider or seek emergency medical help immediately. Symptoms of low blood calcium, such as numbness or tingling in the fingers, toes, or around the mouth, should prompt patients to call their healthcare provider right away. Similarly, any symptoms of nasal irritation, including crusting, dryness, redness or swelling, nose sores (ulcers), or nosebleeds, should be reported immediately. Healthcare providers may need to pause treatment with Calcitonin Salmon Nasal Solution until nasal irritation symptoms resolve.

Finally, patients should be encouraged to contact their healthcare provider promptly if they experience any bothersome side effects or if any side effects persist.

Storage and Handling

The product is supplied in an unopened bottle that must be stored in a refrigerator at a temperature range of 2°C to 8°C (36°F to 46°F). It is essential to avoid freezing the product to maintain its integrity.

Once the bottle is in use, it should be kept at room temperature, specifically between 20°C to 25°C (68°F to 77°F), and stored in an upright position. The product can be used for up to 35 days under these conditions.

It is important to discard the bottle after administering 30 doses to ensure safety and efficacy.

Additional Clinical Information

Periodic nasal examinations are recommended for patients prior to the initiation of treatment with Calcitonin Salmon Nasal Solution, as well as during therapy and whenever nasal symptoms arise. These examinations should include visualization of the nasal mucosa, turbinates, septum, and mucosal blood vessels. Additionally, periodic assessments of urine sediment may be considered.

For patients with suspected hypersensitivity to calcitonin-salmon, skin testing using a dilute, sterile solution of an injectable product should be contemplated before treatment. Healthcare providers may refer patients to an allergist for this testing, with a detailed protocol available from the Medical Services Department of Endo. It is crucial to correct hypocalcemia prior to starting therapy, and to address any other disorders affecting mineral metabolism, such as vitamin D deficiency. During treatment, serum calcium levels and symptoms of hypocalcemia should be monitored, and adequate intake of calcium and vitamin D is recommended.

FDA Insert (PDF)

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

View full prescribing information (PDF)