Calcitonin (Nasal-Systemic)
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VA CLASSIFICATION
Primary: HS900
Commonly used brand name(s): Miacalcin.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Bone resorption inhibitor—
osteoporosis therapy—
Indications
Accepted
Osteoporosis, postmenopausal (treatment adjunct)—Intranasal calcitonin-salmon is indicated for the treatment of osteoporosis in women who are more than 5 years postmenopause and have low bone mass relative to healthy premenopausal women {01}. It is used in conjunction with an adequate intake of calcium (1000 mg of elemental calcium a day) and vitamin D (400 IU a day) {01}. Calcitonin should be reserved for patients who refuse or cannot tolerate estrogens or those in whom estrogens are contraindicated {01}.
—Intranasal calcitonin has been shown to increase spinal bone mass in postmenopausal women with established osteoporosis, but not in early postmenopausal women {01}.
Pharmacology/Pharmacokinetics
Mechanism of action/Effect:
Osteoporosis—Studies using injectable calcitonin have found that it inhibits bone resorption by reducing the number and/or function of osteoclasts {01}. With prolonged injectable calcitonin use, there is a persistent, smaller decrease in the rate of bone resorption {01}. In vitro studies using injectable calcitonin-salmon have found an inhibition of osteoclast function with loss of the ruffled osteoclast border that is responsible for resorption of bone {01}. In vitro studies indicate that calcitonin may augment bone formation by increasing osteoblastic activity {01}. Long-term studies indicate that injectable calcitonin therapy results in the formation of bone that is of normal quality {01}.
Other actions/effects:
There is a slight decrease in serum calcium concentrations associated with intranasal calcitonin-salmon use; however, serum calcium remains within normal limits {01}.
Injectable calcitonin increases the excretion of filtered phosphate, calcium, and sodium by inhibiting their tubular reabsorption {01}.
Short-term administration of injectable calcitonin decreases the volume and acidity of gastric juice, the content of trypsin and amylase, and the volume of pancreatic juice {01}. However, studies have not been conducted with intranasal calcitonin {01}.
Absorption:
Rapidly absorbed by the nasal mucosa {01}.
Half-life:
Elimination—43 minutes after intranasal administration {01}.
Time to peak concentration:
Approximately 31 to 39 minutes after intranasal administration {01}.
Precautions to Consider
Cross-sensitivity and/or related problems
Although not specifically reported for intranasal calcitonin-salmon, patients who are allergic to proteins may be allergic to calcitonin, because calcitonin is a protein {01}. Its use in not recommended in patients with suspected sensitivity to calcitonin who show a positive response to skin testing prior to initiating therapy {01}.
Carcinogenicity
A 1-year toxicity study in Sprague-Dawley and Fischer 344 rats given subcutaneous calcitonin-salmon at doses of 80 IU per kg of body weight a day (16 to 19 times the recommended human parenteral dose and approximately 130 to 160 times the recommended human intranasal dose based on body surface area) found an increased incidence of nonfunctioning pituitary adenomas {01}. It was suggested that calcitonin-salmon reduced the latency period for development of pituitary adenomas that do not produce hormones, probably through the perturbation of physiologic processes involved in the evolution of this commonly occurring endocrine lesion in the rat {01}. Although calcitonin-salmon reduced the latency period, it did not induce the hyperplastic or neoplastic process {01}.
Mutagenicity
Calcitonin-salmon was found nonmutagenic in studies using Salmonella typhimurium (five strains) and Escherichia coli (two strains), both with and without rat liver metabolic activation {01}. Calcitonin-salmon also was found nonmutagenic in an in vitro chromosome aberration test in mammalian V79 cells of the Chinese hamster {01}.
Pregnancy/Reproduction
Pregnancy—
Adequate and well-controlled studies in humans have not been done {01}. Intranasal calcitonin-salmon is not indicated for use in pregnancy {01}.
Reproduction studies in rabbits given injectable calcitonin-salmon in doses ranging from 8 to 33 times the recommended human parenteral dose and 70 to 278 times the recommended human intranasal dose based on body surface area showed a decrease in fetal birth weights {01}. Since calcitonin does not cross the placenta, these effects may have been due to metabolic effects on the pregnant animal {01}.
FDA Pregnancy Category C {01}.
Breast-feeding
It is not known whether intranasal calcitonin-salmon is distributed into human breast milk {01}. Calcitonin has been shown to inhibit lactation in animals {01}.
Pediatrics
There are no data to support the use of intranasal calcitonin-salmon in children {01}.
Geriatrics
Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of intranasal calcitonin-salmon in the elderly {01}.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Bisphosphonates, such as alendronate, etidronate, and pamidronate (prior bisphosphonate use has been reported to reduce the antiresorptive response to intranasal calcitonin-salmon in patients with Paget's disease; however, this effect has not been assessed in postmenopausal women)
{01}
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
» Allergy to proteins (or history of) or
» Sensitivity to calcitonin (although not reported specifically for intranasal calcitonin-salmon, serious systemic allergic reactions [e.g., bronchospasm, swelling of the tongue or throat, anaphylactic shock, death due to anaphylaxis] have been reported with use of injectable calcitonin-salmon; skin testing should be considered prior to treatment of patients with suspected sensitivity to calcitonin-salmon)
{01}
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Alkaline phosphatase, serum and
Hydroxyproline, urinary (effects of intranasal calcitonin-salmon on these markers of bone turnover have not been consistently demonstrated in studies of women with postmenopausal osteoporosis; therefore, these parameters alone should not be used to determine clinical response to calcitonin-salmon; values should decrease with treatment)
{01}
Bone mass (periodic measurements of vertebral bone mass are recommended during treatment to document stabilization of bone loss or increases in bone density; bone mass values should increase with treatment)
{01}
Nasal examinations (nasal examinations should be performed before treatment begins, and at any time that nasal complaints occur; mucosal alterations or transient nasal conditions have been reported in up to 9% of patients receiving intranasal calcitonin-salmon; the examination should consist of visualization of the nasal mucosa, turbinates, and septum and assessment of mucosal blood vessel status; therapy should be discontinued temporarily to allow healing if small ulcers occur, and discontinued permanently if severe ulceration [e.g., ulcers greater than 1.5 mm in diameter, ulcers that penetrate below the mucosa, or ulcers associated with heavy bleeding] occurs)
{01}
Urinalysis (periodic examinations of urine sediment should be considered, since coarse granular casts containing renal tubular epithelial cells were found in the urine of individuals receiving injectable calcitonin-salmon while at bedrest; no urine sediment abnormalities were found in ambulatory patients receiving injectable calcitonin-salmon)
{01}
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
{01} (3 to 12%)
Nasal symptoms, specifically development of crusts
dryness
epistaxis (nose bleeds), inflammation
irritation
itching
redness
rhinitis (runny nose), sores or wounds on nasal mucosa
or tenderness
Note: Patients who develop these nasal symptoms should be examined by their physicians. Development of ulcers on the nasal mucosa may require temporary or permanent discontinuation of intranasal calcitonin-salmon {01}.
Incidence less frequent
{01} (1 to 3%)
Angina (chest pain)
bronchospasm (wheezing or troubled breathing, severe)
cystitis (bloody or cloudy urine; difficult, burning, or painful urination; frequent urge to urinate)
hypertension (dizziness; headaches, severe or continuing)
lymphadenopathy (swollen glands)
respiratory tract infection, upper (chest pain; chills; cough; ear congestion or pain; fever; head congestion; hoarseness or other voice changes; nasal congestion; runny nose; sneezing; sore throat)
Incidence rare
{01} (< 1%)
Allergic reactions, specifically hives, itching, or skin rash
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
{01} (3 to 12%)
Arthralgia (joint pain)
back pain
headache
Incidence less frequent
{01} (1 to 3%) or rare (< 1%)
Abdominal pain
conjunctivitis (burning, dry, or itching eyes)
constipation
diarrhea
dizziness
dyspepsia (upset stomach)
fatigue (unusual tiredness or weakness)
flu-like symptoms
flushing
lacrimation, unusual (unusual tearing of eyes)
mental depression
myalgia (muscle pain)
nausea
skin rash
Overdose
For specific information on the agents used in the management of intranasal calcitonin-salmon overdose, see the Calcium Supplements (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing).
Treatment of overdose
Specific treatment—Administering parenteral calcium if hypocalcemic tetany develops {01}.
Supportive care—Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Calcitonin (Nasal-Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Allergies (history of) or sensitivity to calcitonin or other proteins
Pregnancy—Not indicated for use during pregnancy
Breast-feeding—Lactation inhibited in animal studies
Use in children—No data to support use
Proper use of this medication
» Reading patient instructions carefully
» Importance of not using more medication than the amount prescribed
» Importance of not reactivating pump before daily dose
Assembling the unit (Note: If unit has been assembled by health care professional, this step is not necessary)
» Removing bottle from refrigerator and allowing it to reach room temperature
» Lifting up blue plastic tab and pulling metal safety seal off bottle
» Keeping bottle upright while removing rubber stopper from bottle
» Holding pump unit while removing opaque plastic protective cap from bottom of unit
» Holding bottle upright while inserting nasal spray pump unit into bottle
» Turning pump unit clockwise and tightening until securely fastened
Priming the unit (for first-time use of unit only)
» Holding bottle upright while removing clear protective cap from nozzle
» Depressing the two white side arms several times until a faint spray is emitted
Proper administration
» Blowing nose gently before using spray
» Keeping head in upright position and placing nozzle firmly into one nostril
» Depressing pump toward bottle one time
» Not inhaling while spraying
» Replacing plastic cap
» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose
» Proper storage
Side/adverse effects
Signs of potential side effects, especially nasal symptoms; angina; bronchospasm; cystitis; hypertension; lymphadenopathy; respiratory tract infection, upper; and allergic reaction
General Dosing Information
Skin testing should be considered prior to treatment of patients with suspected sensitivity to calcitonin-salmon {01}. The manufacturer's recommendation for preparing the solution for skin testing is as follows:
• Prepare a dilution of 10 IU per mL by withdrawing 0.05 mL of calcitonin-salmon into a tuberculin syringe {01}.
• Fill syringe to 1 mL with 0.9% sodium chloride injection. Mix well {01}.
• Discard 0.9 mL and inject 0.1 mL intracutaneously on the inner forearm {01}.
• Observe injection site 15 minutes after injection {01}.
• A positive response is considered to be the appearance of erythema or a wheal that is more than mild {01}.
Nasal Dosage Form
CALCITONIN-SALMON NASAL SOLUTION
Usual adult and adolescent dose
Postmenopausal osteoporosis
Intranasal, 200 IU (one metered spray in one nostril) a day, alternating nostrils daily {01}.
Strength(s) usually available
U.S.—
200 IU per metered spray (Rx) [Miacalcin]{01}
Packaging and storage:
The unopened container should be stored between 2 and 8 °C (36 and 46 °F). Protect from freezing {01}.
Stability:
Once the pump has been activated, the bottle may be kept at room temperature until the medication is finished (2 weeks) {01}. Opened or unopened bottles left at room temperature for more than 30 days must be discarded {01}.
Developed: 03/23/1998
References
- Miacalcin product information (Sandoz—US), Rev 9/95, Rec 12/96.
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