Fortical Information
Fortical (Calcitonin) Description
Calcitonin is a polypeptide hormone secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish.
The active ingredient in Fortical (Calcitonin) calcitonin-salmon (rDNA origin) Nasal Spray is a polypeptide of 32 amino acids manufactured by recombinant DNA technology and is identical to calcitonin-salmon produced by chemical synthesis.
This is shown by the following graphic formula:
It is provided in a 3.7 mL fill glass bottle as a solution for intranasal administration with sufficient medication for at least 30 doses. Each spray delivers 200 International Units calcitonin-salmon in a volume of 0.09 mL.
Fortical (Calcitonin) Clinical Pharmacology
Calcitonin acts primarily on bone, but direct renal effects and actions on the gastrointestinal tract are also recognized. Calcitonin-salmon appears to have actions essentially identical to calcitonins of mammalian origin, but its potency per mg is greater and it has a longer duration of action.
The information below, describing the clinical pharmacology of calcitonin, has been derived from studies with calcitonin. The mean bioavailability of calcitonin-salmon nasal spray is approximately 3% of the injectable calcitonin in normal subjects and, therefore, the conclusions concerning the of this preparation may be different.
The actions of calcitonin on bone and its role in normal human bone physiology are still not completely elucidated, although calcitonin receptors have been discovered in osteoclasts and osteoblasts.
Single injections of calcitonin cause a marked transient inhibition of the ongoing bone resorptive process. With prolonged use, there is a persistent, smaller decrease in the rate of bone resorption. Histologically, this is associated with a decreased number of osteoclasts and an apparent decrease in their resorptive activity. studies have shown that calcitonin-salmon causes inhibition of osteoclast function with loss of the ruffled osteoclast border responsible for resorption of bone. This activity resumes following removal of calcitonin-salmon from the test system. There is some evidence from studies that bone formation may be augmented by calcitonin through increased osteoblastic activity.
Animal studies indicate that endogenous calcitonin, primarily through its action on bone, participates with parathyroid hormone in the homeostatic regulation of blood calcium. Thus, high blood calcium levels cause increased secretion of calcitonin which, in turn, inhibits bone resorption. This reduces the transfer of calcium from bone to blood and tends to return blood calcium towards the normal level. The importance of this process in humans has not been determined. In normal adults, who have a relatively low rate of bone resorption, the administration of exogenous calcitonin results in only a slight decrease in serum calcium in the limits of the normal range. In normal children and in patients with Paget's disease in whom bone resorption is more rapid, decreases in serum calcium are more pronounced in response to calcitonin.
Bone biopsy and radial bone mass studies at baseline and after 26 months of daily injectable calcitonin indicate that calcitonin therapy results in the formation of normal bone.
Fortical (Calcitonin) Contraindications
Clinical allergy to calcitonin-salmon.
Fortical (Calcitonin) Precautions
Formal studies designed to evaluate drug interactions with calcitonin-salmon have not been done.
Concomitant use of calcitonin and lithium may lead to a reduction in plasma lithium concentrations due to increased urinary clearance of lithium. The dose of lithium may need to be adjusted.
The effects of prior use of diphosphonates in postmenopausal osteoporosis patients have not been assessed; however, in patients with Paget's disease prior diphosphonate use appears to reduce the anti-resorptive response to calcitonin-salmon nasal spray.
Periodic nasal examinations with visualization of the nasal mucosa, turbinates, septum and mucosal blood vessel status are recommended.
The development of mucosal alterations or transient nasal conditions have been reported in up to 9% of patients who received a calcitonin-salmon nasal spray and in up to 12% of patients who received placebo nasal spray in studies in postmenopausal women. The majority of patients (approximately 90%) in whom nasal abnormalities were noted also reported nasally related complaints/symptoms as adverse events. Therefore, a nasal examination should be performed prior to start of treatment with nasal calcitonin and at any time nasal complaints occur.
In all postmenopausal patients treated with a calcitonin-salmon nasal spray, the most commonly reported nasal adverse events included rhinitis (12%), epistaxis (3.5%), and sinusitis (2.3%). Smoking was shown not to have any contributory effect on the occurrence of nasal adverse events. One patient (0.3%) treated with a calcitonin-salmon nasal spray who was receiving 400 International Units daily developed a small nasal wound. In clinical trials in another disorder (Paget's disease), 2.8% of patients developed nasal ulcerations.
If severe ulceration of the nasal mucosa occurs, as indicated by ulcers greater than 1.5 mm in diameter or penetrating below the mucosa, or those associated with heavy bleeding, calcitonin-salmon nasal spray should be discontinued. Although smaller ulcers often heal without withdrawal of calcitonin-salmon nasal spray, medication should be discontinued temporarily until healing occurs.
Careful instructions on pump assembly, priming of the pump and nasal introduction of Fortical (Calcitonin) calcitonin-salmon (rDNA origin) Nasal Spray should be given to the patient. Although instructions for patients are supplied with the individual bottle, procedures for use should be demonstrated to each patient. Patients should notify their physician if they develop significant nasal irritation.
Get emergency medical help right away if you have any of the following symptoms of a serious allergic reaction:
Patients should be advised of the following:
An increased incidence of non-functioning pituitary adenomas has been observed in 1-year toxicity studies in Sprague-Dawley and Fischer 344 Rats administered (subcutaneously) calcitonin-salmon at dosages of 80 International Units per kilogram per day (16-19 times the recommended human parenteral dose and about 130-160 times the human intranasal dose based on body surface area).
The findings suggest that calcitonin-salmon reduced the latency period for development of the 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. Although administration of calcitonin-salmon reduces the latency period of the development of nonfunctional proliferative lesions in rats, it did not induce the hyperplastic/neoplastic process.
Calcitonin-salmon was tested for mutagenicity using four strains of and two strains of , with and without rat liver metabolic activation, and found to be non-mutagenic. The drug was also not mutagenic in a chromosome aberration test in Chinese Hamster ovary cells .
Fortical (Calcitonin) Adverse Reactions
The incidence of adverse reactions reported in studies involving postmenopausal osteoporotic patients chronically exposed to calcitonin-salmon nasal spray (N=341) and to placebo nasal spray (N=131), and reported in greater than 3% of calcitonin-salmon nasal spray treated patients are presented in the following table. Most adverse reactions were mild to moderate in severity. Nasal adverse events were most common with 70% mild, 25% moderate, and 5% severe in nature (placebo rates were 71% mild, 27% moderate, and 2% severe).
In addition, the following adverse events were reported in fewer than 3% of patients during chronic therapy with calcitonin-salmon nasal spray. Adverse events reported in 1%-3% of patients are identified with an asterisk(*). The remainder occurred in less than 1% of patients. Other than flushing, nausea, possible allergic reactions, and possible local irritative effects in the respiratory tract, a relationship to calcitonin-salmon nasal spray has not been established.
Common adverse reactions associated with the use of injectable calcitonin-salmon occurred less frequently in patients treated with calcitonin-salmon nasal spray than in those patients treated with injectable calcitonin. Nausea, with or without vomiting, which occurred in 1.8% of patients treated with the nasal spray (and 1.5% of those receiving placebo nasal spray) occurs in about 10% of patients who take injectable calcitonin-salmon. Flushing, which occurred in less than 1% of patients treated with the nasal spray, occurs in 2-5% of patients treated with injectable calcitonin-salmon. Although the administered dosages of injectable and nasal spray calcitonin-salmon are comparable (50-100 units daily of injectable versus 200 units daily of nasal spray), the nasal dosage form has a mean bioavailability of about 3% (range 0.3%-30.6%) and therefore provides less drug to the systemic circulation, possibly accounting for the decrease in frequency of adverse reactions.
The collective foreign marketing experience with calcitonin-salmon nasal spray does not show evidence of any notable difference in the incidence profile of reported adverse reactions when compared with that seen in the clinical trials.
Fortical (Calcitonin) Overdosage
No instances of overdose with calcitonin-salmon nasal spray have been reported and no serious adverse reactions have been associated with high doses. There is no known potential for drug abuse for calcitonin-salmon.
Single doses of calcitonin-salmon nasal spray up to 1600 International Units, doses up to 800 International Units per day for 3 days and chronic administration of doses up to 600 International Units per day have been studied without serious adverse effects. A 1000 International Units dose of calcitonin-salmon injectable product given subcutaneously may produce nausea and vomiting. A 32 International Units per kg per day dose of calcitonin-salmon injectable product for 1or 2 days demonstrated no additional adverse effects.
There have been no reports of hypocalcemic tetany. However, the pharmacologic actions of Fortical (Calcitonin) calcitonin-salmon (rDNA origin) Nasal Spray suggest that this could occur in overdose. Therefore, provisions for parenteral administration of calcium should be available for the treatment of overdose.
Fortical (Calcitonin) Dosage And Administration
The recommended dose of Fortical (Calcitonin) calcitonin-salmon (rDNA origin) Nasal Spray in postmenopausal osteoporotic patients is 1 spray (200 International Units) per day administered intranasally, alternating nostrils daily. Each bottle, filled with 3.7 mL of solution, contains enough medication for 30 doses. Drug effect may be monitored by periodic measurements of lumbar vertebral bone mass to document stabilization of bone loss or increases in bone density. Effects of calcitonin-salmon nasal spray on biochemical markers of bone turnover have not been consistently demonstrated in studies in postmenopausal osteoporosis. Therefore, these parameters should not be solely utilized to determine clinical response to calcitonin-salmon nasal spray therapy in these patients.
Fortical (Calcitonin) How Supplied
Fortical (Calcitonin) calcitonin-salmon (rDNA origin) Nasal Spray is presented as a metered dose solution in a 3.7 mL fill amber glass bottle. It is available in a dosage strength of 200 International Units per activation (0.09 mL). A screw-on pump is provided. Following priming, the pump will deliver solution containing 200 International Units of calcitonin-salmon per activation. Fortical (Calcitonin) calcitonin-salmon (rDNA origin) Nasal Spray contains 2200 International Units/mL calcitonin-salmon and is provided in individual boxes containing one glass bottle with screw cap and one screw-on pump (NDC# 0245-0008-35).
Fortical (Calcitonin)
Fortical (Calcitonin) Forticalcalcitonin-salmon (rdna Origin)nasal Spray
Read the Patient Information that comes with Fortical (Calcitonin) Nasal Spray before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.
Fortical (Calcitonin) Nasal Spray is a prescription medicine used to treat osteoporosis in women, who went through menopause (postmenopausal women) at least 5 years ago.
Fortical (Calcitonin) Nasal Spray contains calcitonin salmon, a man-made protein that is similar to a protein occurring in the human body. When you spray Fortical (Calcitonin) Nasal Spray into your nostril, it is rapidly absorbed by the blood vessels lining your nasal passages. It then travels into your bloodstream and on to your bones where it has been shown to slow down bone loss at the spine. Slowing down bone loss, while new bone building continues, helps to increase bone mass at the spine.
Fortical (Calcitonin) Nasal Spray is taken with calcium and vitamin D supplements recommended by your doctor, to help slow down further bone loss. If you are not getting enough calcium and vitamin D in your daily diet, your doctor may recommend a calcium or vitamin D supplement. The amount of calcium and vitamin D needed each day can vary from person to person. Most people generally require at least 1000 mg of calcium and 400 International Units of vitamin D each day. Vitamin D is necessary for your body to use calcium to build bone material. That is why your doctor may have recommended that you add a vitamin D supplement to your diet. It is important to take all the calcium and vitamin D supplements your doctor directs each day.
Do not use Fortical (Calcitonin) Nasal Spray if you are allergic to the calcitonin salmon protein.
Tell your doctor about all your health conditions, including if you:
Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.
Serious allergic reactions can happen with Fortical (Calcitonin) Nasal Spray. See .
Get emergency medical help right away if you have any of the following symptoms of a serious allergic reaction:
The most common side effects of Fortical (Calcitonin) Nasal Spray include:
Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Fortical (Calcitonin) Nasal Spray. For more information, ask your doctor or pharmacist.
Active Ingredient: Calcitonin-salmon
Inactive Ingredients: Sodium Chloride USP, Citric Acid USP, Phenethyl Alcohol USP, Benzyl Alcohol NF, Polysorbate 80 NF, Hydrochloric Acid NF or Sodium Hydroxide NF and Purified Water USP.
This medication was prescribed for you by your doctor for a particular condition. Do not use Fortical (Calcitonin) Nasal Spray to treat a condition for which it was not prescribed. Do not give Fortical (Calcitonin) Nasal Spray to other people, even if they have the same symptoms you have. It may harm them.
This patient information leaflet summarizes the most important information about Fortical (Calcitonin) Nasal Spray. If you would like more information about Fortical (Calcitonin) Nasal Spray talk with your doctor. You can ask your doctor or pharmacist for information about Fortical (Calcitonin) Nasal Spray that is written for health professionals. For more information, go to or call 1-800-654-2299.
The amount of estrogen produced by a woman's body is greatly reduced after menopause. Estrogen helps to balance bone growth and keep bones strong. When estrogen is reduced, your body may remove old bone cells faster than it replaces them with new bones cells. Bones can become weak and brittle, and more likely to break (fracture). This condition is known as postmenopausal osteoporosis. Fortical (Calcitonin) Nasal Spray may increase bone density, but there is no information to show that it decreases the risk of fracture.
Assembly Instructions
Store Fortical (Calcitonin) Nasal Spray in an upright position. Tighten the pump securely to the bottle (see and in the Patient Instructions for Use). This will help to ensure a good seal between the pump and the bottle.
Toll Free 1-800-654-2299
103001-01Revised 0609
Fortical (Calcitonin) Principal Display Panel - Iu/ml Carton
NDC 0245-0008-35
30 dosesEach carton contains:1 × 3.7 mL fill bottle and1 spray applicator
