Fortical

The following serious adverse reactions are discussed in greater detail in other sections of the label:

• Hypersensitivity Reactions, including anaphylaxis [see WARNINGS AND PRECAUTIONS]
• Hypocalcemia [see WARNINGS AND PRECAUTIONS]
• Nasal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Malignancy [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of calcitonin-salmon nasal spray in the treatment of postmenopausal osteoporosis was assessed in 5 randomized, double-blind, placebo controlled trials that enrolled postmenopausal women, aged 45-75 years. The duration of the trials ranged from 1 to 2 years. 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 treated patients are presented in the following table. 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.

Table 1: Adverse Reactions Occurring in at Least 3% of Postmenopausal Patients Treated Chronically

Nasal Adverse Reactions: In all postmenopausal patients treated with calcitonin-salmon nasal spray, the most commonly reported nasal adverse reactions included rhinitis (12%), epistaxis (4%), and sinusitis (2%). Smoking did not have a contributory effect on the occurrence of nasal adverse reactions.

Adverse reactions reported in 1-3% of patients treated with calcitonin-salmon nasal spray include: influenza-like symptoms, erythematous rash, arthrosis, myalgia, sinusitis, upper respiratory tract infection, bronchospasm, abdominal pain, nausea, dizziness, paresthesia, abnormal lacrimation, conjunctivitis, lymphadenopathy, infection, and depression.

A meta-analysis of 21 randomized, controlled clinical trials with calcitonin-salmon (nasal spray or investigational oral formulations) was conducted to assess the risk of malignancies in calcitonin-salmon-treated patients compared to placebo-treated patients. The trials in the metaanalysis ranged in duration from 6 months to 5 years and included a total of 10883 patients (6151 treated with calcitonin-salmon and 4732 treated with placebo). The overall incidence of malignancies reported in these 21 trials was higher among calcitonin-salmon-treated patients (254/6151 or 4.1%) compared with placebo-treated patients (137/4732 or 2.9%). Findings were similar when analyses were restricted to the 18 nasal spray only trials [calcitonin-salmon 122/2712 (4.5%); placebo 30/1309 (2.3%)].

The meta-analysis results suggest an increased risk of overall malignancies in calcitonin-salmontreated patients compared to placebo-treated patients when all 21 trials are included and when the analysis is restricted to the 18 nasal spray only trials (see Table 2). It is not possible to exclude an increased risk when calcitonin-salmon is administered by the subcutaneous, intramuscular, or intravenous route because these routes of administration were not investigated in the meta analysis. The increased malignancy risk seen with the meta-analysis was heavily influenced by a single large 5-year trial, which had an observed risk difference of 3.4% [95% CI (0.4%, 6.5%)]. Imbalances in risks were still observed when analyses excluded basal cell carcinoma (see Table 2); the data were not sufficient for further analyses by type of malignancy. A mechanism for these observations has not been identified. Although a definitive causal relationship between calcitonin-salmon use and malignancies cannot be established from this meta-analysis, the benefits for the individual patient should be carefully evaluated against all possible risks [see WARNINGS AND PRECAUTIONS].

Table 2: Risk Difference for Malignancies in Calcitonin-Salmon-Treated Patients Compared with Placebo-Treated Patients

Postmarketing Experience

Because postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported during post-approval use of calcitoninsalmon nasal spray.

Allergic / Hypersensitivity Reactions: Serious allergic reactions have been reported in patients receiving calcitonin-salmon nasal spray, including anaphylaxis and anaphylactic shock.

Hypocalcemia: Hypocalcemia with paresthesia has been reported.

Body as a whole: facial or peripheral edema

Cardiovascular: hypertension, vasodilatation, syncope, chest pain

Nervous system: dizziness, seizure, visual or hearing impairment, tinnitus

Respiratory/ Special Senses: cough, bronchospasm, dyspnea, loss of taste/smell

Skin: rash/dermatitis, pruritus, alopecia, increased sweating

Gastrointestinal: diarrhea

Nervous system disorders: tremor

Immunogenicity

Consistent with the potentially immunogenic properties of medicinal products containing peptides, administration of Fortical may trigger the development of anti-calcitonin antibodies. In a two-year calcitonin-salmon nasal spray clinical study that evaluated immunogenicity, a measurable antibody titer was found in 69% of patients treated with calcitonin-salmon and 3% of placebo-treated patients. Antibody formation may be associated with a loss of response to treatment [see WARNINGS AND PRECAUTIONS].

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of a positive antibody test result may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of antibodies to calcitonin-salmon nasal spray with the incidence of antibodies to other calcitonin-containing products may be misleading.

Fortical
[for-ti-kal]
(calcitonin-salmon [rDNA origin]) Nasal Spray

Read this Patient Information before you start using Fortical Nasal Spray and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is Fortical Nasal Spray?

Fortical Nasal Spray is a prescription medicine used to treat osteoporosis in women more than 5 years after menopause. Fortical Nasal Spray should be used for women who cannot use other treatments or who choose not to use other treatments for osteoporosis.

It is not known if Fortical Nasal Spray lowers the chance of having bone fractures.

Calcitonin-salmon the active ingredient in Fortical Nasal Spray has not been shown to be effective in women less than 5 years after menopause.

It is not known if Fortical Nasal Spray is safe and effective in children under 18 years of age.

Who should not use Fortical Nasal Spray?

Do not use Fortical Nasal Spray if you:

• are allergic to calcitonin-salmon or any of the ingredients in Fortical Nasal Spray. See the end of this leaflet for a complete list of ingredients in Fortical Nasal Spray.

What should I tell my healthcare provider before using Fortical Nasal Spray?

Before you use Fortical Nasal Spray, tell your healthcare provider if you:

• have any other medical conditions
• have low calcium levels in your blood
• are pregnant or plan to become pregnant. It is not known if Fortical Nasal Spray can harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if Fortical Nasal Spray passes into your breast milk. You and your healthcare provider should decide if you will use Fortical Nasal Spray or breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Especially tell your healthcare provider if you take:

• lithium. Your healthcare provider may need to change your dose of lithium while you use Fortical Nasal Spray.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I use Fortical Nasal Spray?

• For detailed instructions, see the Instructions for Use at the end of this Patient Information leaflet.
• Use Fortical Nasal Spray exactly as your healthcare provider tells you to use it.
• Do not use Fortical Nasal Spray until your healthcare provider shows you and you understand how to use it correctly.
• Use 1 spray of Fortical Nasal Spray, 1 time each day, in 1 nostril (inside your nose).
  • Start with 1 spray in your left nostril on your first day, followed by 1 spray in your right nostril on the second day.
  • Continue to switch nostrils for your dose each day.
• Your healthcare provider should check your nose before you start using Fortical Nasal Spray and often while you are using it.
• Tell your healthcare provider if you start to have discomfort  (irritation) in your nose that bothers you while you use Fortical Nasal Spray.
• Your healthcare provider should prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you use Fortical Nasal Spray.
• Take your calcium and vitamin D as your healthcare provider tells you to.
• There are 30 doses (sprays) of Fortical Nasal Spray in each bottle. After 30 doses, each spray may not give you the right amount of medicine, even if the bottle is not completely empty. Keep track of the number of doses of medicine used from your bottle.
• If you use too much Fortical Nasal Spray, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of Fortical Nasal Spray?

Fortical Nasal Spray may cause serious side effects, including:

• allergic reactions. Some people have had an allergic reaction when using Fortical Nasal Spray. Some reactions may be serious and can be life threatening. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of these symptoms of an allergic reaction.
  • trouble breathing
  • swelling of your face, throat or tongue
  • fast heartbeat
  • chest pain
  • feel dizzy or faint
    If you might be allergic to calcitonin-salmon, your healthcare provider should do a skin test before you use Fortical Nasal Spray.
• low calcium levels in your blood (hypocalcemia). Fortical Nasal Spray may lower the calcium in your blood. If you have low blood calcium before you start using Fortical Nasal Spray, it may get worse during treatment. Your low blood calcium must be treated before you use Fortical Nasal Spray. Most people with low blood calcium levels do not have symptoms, but some people may have symptoms. Call your healthcare provider right away if you have any of these symptoms of low blood calcium:
  • numbness or tingling in your fingers, toes, or around your mouth

Your healthcare provider should:

• do blood tests while you use Fortical Nasal Spray
• prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you use Fortical Nasal Spray.

Take your calcium and vitamin D as your healthcare provider tells you to.

• nose irritation
  Irritation of your nose can happen while you are using Fortical Nasal Spray, especially if you are over 65 years of age. Call your healthcare provider right away if you have any of these symptoms of nose irritation:
  • crusting
  • dryness
  • redness or swelling
  • nose sores (ulcers)
  • nose bleeds

Your healthcare provider may stop your treatment with Fortical Nasal Spray until your nose irritation symptoms go away.

• risk of cancer
  People who use calcitonin-salmon, the medicine in Fortical Nasal Spray, may have an increased risk of cancer. Your healthcare provider should check while you are using Fortical to see if it is still right for you.
• increase of certain cells (sediment) in your urine
  Your healthcare provider should test your urine often while you are using Fortical Nasal Spray.

The most common side effects of Fortical® Nasal Spray include:

• runny nose
• nose bleeds
• nasal problems
• back pain
• muscle pain
• headache

These are not all the possible side effects of Fortical Nasal Spray. For more information, ask your healthcare provider or pharmacist.

Tell your healthcare provider right away if you have any side effect that bothers you or does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store Fortical Nasal Spray?

• Store open bottles of Fortical Nasal Spray at room temperature, 68°F to 77°F (20°C to 25°C).
• Store unopened bottles of Fortical Nasal Spray in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze.
• Store Fortical Nasal Spray bottles in an upright position.
• Safely throw away Fortical Nasal Spray in the trash after you have used 30 doses (sprays).

Keep Fortical Nasal Spray and all other medicines out of the reach of children.

General Information about the safe and effective use of Fortical Nasal Spray.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Fortical Nasal Spray for a condition for which it was not prescribed. Do not give Fortical 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 importantinformation about Fortical Nasal Spray. If you would like moreinformation about Fortical Nasal Spray talk with your healthcareprovider. You can ask your pharmacist or healthcare provider forinformation about Fortical Nasal Spray that is written for healthprofessionals.

For more information, go to www.upsher-smith.com or call 1-888650-3789.

What are the ingredients in Fortical Nasal Spray?

Active Ingredient: calcitonin-salmon

Inactive Ingredients: sodium chloride, citric acid, phenylethyl alcohol, benzyl alcohol, polysorbate 80, hydrochloric acid or sodium hydroxide and purified water.

Instructions for Use

Fortical
[for-ti-kal]
(calcitonin-salmon [rDNA origin]) Nasal Spray

For Nasal Use

Only Important information about your Fortical Nasal Spray:

• A single spray of Fortical Nasal Spray contains 1 daily dose ofmedicine.
• Each Fortical Nasal Spray bottle contains the right amount of medicine. The bottle may not be completely filled to the top. This is normal.
• This package contains 1 bottle of Fortical Nasal Spray and 1 screw-on pump.

• Store unopened bottles of Fortical Nasal Spray in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze.
• After you open your bottle of Fortical Nasal Spray, store it at room temperature between 68°F to 77°F (20°C to 25°C) in an upright position. Do not shake the bottle.

Preparing your Fortical Nasal Spray

Remove the bottle from your refrigerator and let it reach room temperature.

Step 1.Opening the Bottle. Set bottle on a flat surface like a table or counter top. Hold the bottle firmly while unscrewing the cap to avoid spilling any Fortical Nasal Spray.

Important: If your pharmacist attached the pump for you, skip to Step 4.

Step 2. Unwrapping the Pump. Carefully cut the wrapper with scissors or knife, and tear away from the pump. Be careful not to cut, bend, or touch the feed tube at the bottom.

Step 3. Attaching the Pump. Hold the bottle on a flat surface (like a table), and screw the pump onto bottle by gripping the grooves of the pump and twisting clockwise until the pump is tightly sealed to the bottle.

Step 4. Removing Cap. To remove the cap from the pump, twist slightly while pulling up. Save the cap to replace after each use.

Step 5. Removing the Lock Tab. Grasp the lock tab between the thumb and forefinger, while holding the bottle on a flat surface. Pull sideways to remove the tab and unlock the pump.

Step 6. Prime New Pump Before First Use. Before you use a new bottle of Fortical Nasal Spray for the first time, you will need to prime it. This will make sure you get the right dose of medicine each time you use it. After you attach the pump to the bottle, and the pump and bottle have reached room temperature, you should:

• Hold the bottle upright.
• With your index and middle fingers on each side of the top of the pump, and with your thumb under the bottle, push the pump down.
• Push the pump down at least 5 times, until you see a full spray.
• If the pump is not delivering a full spray during or after priming, contact Upsher-Smith at 1888-650-3789. Do not place anything into the opening of the pump.

You only need to prime a new bottle. Do not re-prime it before each use.

Step 7. Using Fortical Nasal Spray

• Change (alternate) between using the right nostril 1 day and the left nostril the next day.
• Hold your head and the bottle in an upright, vertical position. Put the spray tip into your nostril at the same angle as your nasal passage.
• Press the pump all the way down 1 time. You do not need to inhale.
• If you do not hold the bottle upright during use, the pump may not be able to give you the right dose of medicine.
• Do not waste medication by testing the sprayer. It is all right if some of the spray drips out of your nostril. 1 spray will give you the correct daily dose of Fortical Nasal Spray.

Step 8. Replace The Lock Tab After Use Then Clean the Spray Tip.

• Replace the lock tab to prevent wasting medicine by accidently depressing the pump. Simply slide the lock tab on by pushing it sideways against the grooves in the pump.
• Clean the spray tip by gently wiping it with a clean, damp cloth or tissue. Dry the tip with a cloth or tissue before replacing the cap. Do not place the tip or bottle in water.

Step 9. Replace The Cap.

Hold the top of the pump as shown and slide the cap back over the tip carefully.

Do not put the Fortical Nasal Spray back in the refrigerator

Step 10. Storing your Fortical Nasal Spray. Store Fortical Nasal Spray in an upright position. Tighten the pump securely to the bottle (see Step 3 and 4 in the Patient Instructions for Use). This will help to make sure there is a good seal between the pump and the bottle.

When should I throw away Fortical Nasal Spray?

• Unopened, refrigerated bottles can be used until the expiration date stamped on the bottle and box.
• Throw away Fortical Nasal Spray after you use 30 doses (sprays).

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

• Upsher-Smith Laboratories, Inc.

Calcitonin has not been studied in pregnant women and may not be safe for use during pregnancy. This medication is not approved for women who are premenopausal, including pregnant women. Tell your healthcare provider if you are pregnant or plan to become pregnant.

Nasal Spray

A single spray contains one daily dose, which is 200 I.U. of calcitonin-salmon. The fine mist is actually 0.09 mL (milliliter) of solution. Your bottle of calcitonin nasal spray contains at least 30 doses. Priming the pump does not alter the total number of doses available in a bottle of calcitonin nasal spray. The bottle need only be primed once after assembly. Do not re-prime or “test spray” your bottle before you use your daily dose of calcitonin nasal spray. This will waste your medication.

Calcitonin is a man-made form of a hormone that occurs naturally in the thyroid gland.

Calcitonin nasal is used to treat osteoporosis in women who have been in menopause for at least 5 years.

Calcitonin nasal may also be used for purposes not listed in this medication guide.

• If you have an allergy to calcitonin or any other part of Fortical (calcitonin-salmon nasal spray).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have low calcium levels.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Fortical with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Very bad and sometimes deadly allergic side effects have rarely happened. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Follow the diet and workout plan that your doctor told you about.
• Take calcium and vitamin D as you were told by your doctor.
• This medicine may add to the chance of getting some types of cancer. Talk with the doctor.
• If you are taking lithium, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with Fortical.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Fortical while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nose irritation.
• Runny nose.
• Back pain.
• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Allergic Reactions

Because calcitonin is a polypeptide, the possibility of a systemic allergic reaction exists. A few cases of serious allergic-type reactions have been reported in patients receiving calcitonin-salmon nasal spray, including cases of anaphylaxis and anaphylactic shock. With injectable calcitonin-salmon there have been a few reports of serious allergic-type reactions (e.g. bronchospasm, swelling of the tongue or throat, anaphylactic shock), including very rare reports of death attributed to anaphylaxis. The usual provisions should be made for emergency treatment if such a reaction should occur. Allergic reactions should be differentiated from generalized flushing and hypotension.

For patients with suspected sensitivity to calcitonin, skin testing should be considered prior to treatment utilizing a dilute, sterile solution of a calcitonin-salmon injectable product. Physicians may wish to refer patients who require skin testing to an allergist. A detailed skin testing protocol is available from Upsher-Smith Laboratories, Inc. by calling toll-free at 1-800-654-2299.

1. Drug Interactions

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.

2. Periodic Nasal Examinations

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.

3. Information for Patients

Careful instructions on pump assembly, priming of the pump and nasal introduction of Fortical® 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:

• trouble breathing
• swelling of your face, throat or tongue
• rapid heartbeat
• chest pain
• feel faint or dizzy

Patients should be advised of the following:

• Store new, unassembled bottles in the refrigerator between 36-46°F (2-8°C).
• Protect the product from freezing.
• Keep the bottle of Fortical® Nasal Spray away from light.
• Before priming the pump and using a new bottle, allow it to reach room temperature.
• After opening a new bottle of Fortical® Nasal Spray, store bottle in use with pump attached at room temperature, 68°F to 77°F (20°C to 25°C), in an upright position. Each bottle contains enough medicine for 30 doses.
• Throw away the empty bottle of Fortical® Nasal Spray after you have used 30 doses.
• See DOSAGE AND ADMINISTRATION, Priming (Activation) of Pump for complete instructions on priming the pump and administering Fortical® calcitonin-salmon (rDNA origin) Nasal Spray.

4. Carcinogenicity, Mutagenicity, Impairment of Fertility

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 Salmonella typhimurium and two strains of Escherichia coli, 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 in vitro.

5. Laboratory Tests

Urine sediment abnormalities have not been reported in ambulatory volunteers treated with calcitonin-salmon nasal spray. Coarse granular casts containing renal tubular epithelial cells were reported in young adult volunteers at bed rest who were given injectable calcitonin-salmon to study the effect of immobilization on osteoporosis. There was no evidence of renal abnormality and the urine sediment became normal after calcitonin was stopped. Periodic examinations of urine sediment should be considered.

6. Pregnancy

Category C

Calcitonin-salmon has been shown to cause a decrease in fetal birth weights in rabbits when given by injection in doses 8-33 times the parenteral dose and 70-278 times the intranasal dose recommended for human use based on body surface area.

Since calcitonin does not cross the placental barrier, this finding may be due to metabolic effects on the pregnant animal. There are no adequate and well-controlled studies in pregnant women with calcitonin-salmon. Fortical® calcitonin-salmon (rDNA origin) Nasal Spray is not indicated for use in pregnancy.

7. Nursing Mothers

It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on this drug since many drugs are excreted in human milk. Calcitonin has been shown to inhibit lactation in animals.

8. Pediatric Use

There are no data to support the use of Fortical® calcitonin-salmon (rDNA origin) Nasal Spray in children. Disorders of bone in children referred to as idiopathic juvenile osteoporosis have been reported rarely. The relationship of these disorders to postmenopausal osteoporosis has not been established and experience with the use of calcitonin in these disorders is limited.

9. Geriatric Use

In a large multi-centered, double-blind, randomized clinical study of calcitonin-salmon nasal spray, 279 patients were less than 65 years old, while 467 patients were 65 to 74 years old and 196 patients were 75 and over. Compared to subjects less than 65 years old, the incidence of nasal adverse events (rhinitis, irritation, erythema, and excoriation) was higher in patients over the age of 65, particularly those over the age of 75. Most events were mild in intensity. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Other drugs may interact with calcitonin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.