FDA label 495988fd-328f-485b-9dc8-cfc1a47baa05

WARNINGS 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 the emergency treatment of such a reaction should it 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 calcitonin-salmon injection. Physicians may wish to refer patients who require skin testing to an allergist. A detailed skin testing protocol is available from the Drug Safety Department of Par Pharmaceutical Companies Inc. at 1-800-828-9393.

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 below 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). Adverse Reactions Occurring in at Least 3%Of Postmenopausal Patients Treated Chronically † Symptom of nose includes: nasal crusts, dryness, redness or erythema, nasal sores, irritation, itching, thick feeling, soreness, pallor, infection, stenosis, runny/blocked, small wound, bleeding wound, tenderness, uncomfortable feeling and sore across bridge of nose. Calcitonin-Salmon Nasal Spray N = 341 Placebo N = 131 Adverse Reaction % of Patients % of Patients Rhinitis 12.0 6.9 Symptom of Nose† 10.6 16.0 Back Pain 5.0 2.3 Arthralgia 3.8 5.3 Epistaxis 3.5 4.6 Headache 3.2 4.6 Body as a whole – General Disorders: influenza-like symptoms*, fatigue*, edema (facial, peripheral and generalized), fever Integumentary: erythematous rash*, skin ulceration, eczema, alopecia, pruritus, increased sweating Musculoskeletal/Collagen: arthrosis*, myalgia*, arthritis, polymyalgia rheumatica, stiffness Respiratory/Special Senses : sinusitis*, upper respiratory tract infection*, bronchospasm*, pharyngitis, bronchitis, pneumonia, coughing, dyspnea, taste perversion, parosmia, nasal congestion, sneezing, allergic rhinitis, nasal odor, mucosal excoriation, rhinitis ulcerative Cardiovascular: hypertension*, angina pectoris*, tachycardia, palpitation, bundle branch block, myocardial infarction Gastrointestinal: dyspepsia*, constipation*, abdominal pain*, nausea*, diarrhea*, vomiting, flatulence, increased appetite, gastritis, dry mouth Liver/Metabolic: cholelithiasis, hepatitis, thirst, weight increase Endocrine: goiter, hyperthyroidism Urinary System: cystitis*, pyelonephritis, hematuria, renal calculus Central and Peripheral Nervous System: dizziness*, paresthesia*, vertigo, migraine, neuralgia, agitation Hearing/Vestibular: tinnitus, hearing loss, earache Vision: abnormal lacrimation*, conjunctivitis*, blurred vision, vitreous floater, visual disturbance Vascular: flushing, cerebrovascular accident, thrombophlebitis Hematologic/Resistance Mechanisms: lymphadenopathy*, infection*, anemia Psychiatric: depression*, insomnia, anxiety, anorexia Immune system disorders: Hypersensitivity, anaphylaxis and anaphylactic shock 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.

<table ID="inv-59095087-1510-469b-85ef-5e70f7049437" frame="border" border="1"> <caption ID="inv-c22bd266-dd02-4b74-8971-6bc70fc9cb5c">Adverse Reactions Occurring in at Least 3%Of Postmenopausal Patients Treated Chronically</caption> <col width="196px"/> <col width="196px"/> <col width="196px"/> <tfoot> <tr> <td colspan="3"> <paragraph styleCode="footnote">&#x2020; Symptom of nose includes: nasal crusts, dryness, redness or erythema, nasal sores, irritation, itching, thick feeling, soreness, pallor, infection, stenosis, runny/blocked, small wound, bleeding wound, tenderness, uncomfortable feeling and sore across bridge of nose.</paragraph> </td> </tr> </tfoot> <tbody> <tr> <td align="center" colspan="3" styleCode="Botrule Lrule Rrule"> <content styleCode="bold">Calcitonin-Salmon</content> </td> </tr> <tr> <td align="center" styleCode="Botrule Lrule Rrule"> <content styleCode="bold"> </content> </td> <td align="center" styleCode="Botrule Rrule"> <content styleCode="bold">Nasal Spray</content> <content styleCode="bold">N = 341</content> </td> <td align="center" styleCode="Botrule Rrule"> <content styleCode="bold">Placebo</content> <content styleCode="bold">N = 131</content> </td> </tr> <tr> <td align="center" styleCode="Botrule Lrule Rrule"> <content styleCode="bold">Adverse Reaction</content> </td> <td align="center" styleCode="Botrule Rrule"> <content styleCode="bold">% of Patients</content> </td> <td align="center" styleCode="Botrule Rrule"> <content styleCode="bold">% of Patients</content> </td> </tr> <tr> <td styleCode="Botrule Lrule Rrule">Rhinitis</td> <td align="center" styleCode="Botrule Rrule">12.0</td> <td align="center" styleCode="Botrule Rrule">6.9</td> </tr> <tr> <td styleCode="Botrule Lrule Rrule">Symptom of Nose&#x2020;</td> <td align="center" styleCode="Botrule Rrule">10.6</td> <td align="center" styleCode="Botrule Rrule">16.0</td> </tr> <tr> <td styleCode="Botrule Lrule Rrule">Back Pain</td> <td align="center" styleCode="Botrule Rrule">5.0</td> <td align="center" styleCode="Botrule Rrule">2.3</td> </tr> <tr> <td styleCode="Botrule Lrule Rrule">Arthralgia</td> <td align="center" styleCode="Botrule Rrule">3.8</td> <td align="center" styleCode="Botrule Rrule">5.3</td> </tr> <tr> <td styleCode="Botrule Lrule Rrule">Epistaxis</td> <td align="center" styleCode="Botrule Rrule">3.5</td> <td align="center" styleCode="Botrule Rrule">4.6</td> </tr> <tr> <td styleCode="Botrule Lrule Rrule">Headache</td> <td align="center" styleCode="Botrule Rrule">3.2</td> <td align="center" styleCode="Botrule Rrule">4.6</td> </tr> </tbody> </table>