Stimate

5 WARNINGS AND PRECAUTIONS Hyponatremia : Excessive fluid intake when urine output is limited by the antidiuretic effect of desmopressin may lead to water intoxication with hyponatremia. ( 5.1 ) Hypotension and Hypertension : May cause hypotension with compensatory increase in heart rate or hypertension. Monitor blood pressure during STIMATE administration, especially in patients with heart disease. ( 5.2 ) Altered Absorption in Patients with Nasal Mucosa Abnormalities: changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption. ( 5.3 ) Hypersensitivity Reactions : Severe reactions have occurred. Monitor for reactions during administration and interrupt if reaction occurs. ( 5.4 ) Increased Risk of Thrombosis in Patients with von Willebrand’s Disease Type IIB : Use of STIMATE in patients with Type IIB von Willebrand’s disease may cause thrombosis due to platelet aggregation. ( 5.5 ) 5.1 Hyponatremia Serious and fatal hyponatremia may occur with STIMATE use. STIMATE is contraindicated in patients with hyponatremia (or a history of it) and known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion [see Contraindications ( 4 )] . Excessive fluid intake when urine output is limited by the antidiuretic effect of desmopressin may lead to water intoxication with hyponatremia. Cases of hyponatremia have been reported from post-marketing experience in patients treated with desmopressin acetate. Unless properly diagnosed and treated, hyponatremia can be fatal. Observe patients receiving STIMATE for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, malaise, fatigue, lethargy, disorientation, depressed reflexes, loss appetite, irritability, muscle weakness, muscle spasms or cramps, and abnormal mental status such as hallucinations, decreased consciousness, and confusion. Severe symptoms due to an extreme decrease in serum sodium and plasma osmolality may include one or a combination of the following: seizure, coma, and/or respiratory arrest. Advise patients to restrict fluids in order to decrease the risk of water intoxication with hyponatremia. Careful fluid intake restriction is particularly important in pediatric and geriatric patients because these patients are at greater risk of developing hyponatremia [see Use in Specific Populations ( 8.4 , 8.5 )]. More frequent monitoring of serum sodium levels is recommended in the following patients: those with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, heart failure, renal disorders, habitual or psychogenic polydipsia or those taking concomitant drugs that may cause hyponatremia or are known to induce SIADH . 5. 2 Hypotension and Hypertension STIMATE may cause changes in blood pressure. Changes have included elevation or reduction in blood pressure which may also cause a compensatory increase in heart rate. Monitor blood pressure and pulse more frequently if used in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease. 5. 3 Altered Absorption in Patients with Nasal Mucosa Abnormalities Since STIMATE is used intranasally, changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption in which case STIMATE should be discontinued until the nasal problems resolve. Avoid use of STIMATE in such patients and consider use of other formulations of desmopressin acetate given by other routes of administration [see Dosage and Administration ( 2.4 )] . 5.4 Hypersensitivity Reactions STIMATE is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of STIMATE [see Contraindications ( 4 )] . Severe allergic reactions, including fatal anaphylaxis, have been reported with desmopressin. It is not known whether antibodies to desmopressin acetate are produced after repeated administration. 5.5 Increased Risk of Thrombosis in Patients with von Willebrand’s Disease Type IIB STIMATE is contraindicated in patients with Type IIB von Willebrand's disease [see Contraindications ( 4 )] . Use of STIMATE in patients with Type IIB von Willebrand’s disease may result in platelet aggregation, thrombocytopenia, and possibly thrombosis.

6 ADVERSE REACTIONS The following serious reactions are described below and elsewhere in the labeling: Hyponatremia [see Warnings and Precautions ( 5.1 )]. Hypotension and Hypertension [see Warnings and Precautions ( 5.2 )] . Altered Absorption in Patients with Changes in Nasal Mucosa [see Warnings and Precautions ( 5.3 )] . Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] . Increased Risk of Thrombosis in Patients with von Willebrand’s Disease Type IIB [see Warnings and Precautions ( 5.5 )] . The following adverse reactions have been identified during post-approval use of desmopressin acetate intranasal formulations. Because these 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: Cardiac disorders : Tachycardia, palpitations Eye disorders : Eye redness, eye itchiness, light sensitivity Gastrointestinal disorders : Nausea*, abdominal cramps/pain*, dyspepsia General disorders and administration site conditions : Peripheral edema*, fatigue*, chills, chest pain Immune system disorders : Hypersensitivity reactions Investigations : Weight increased* Metabolism and nutrition disorders : Hyponatremia Nervous system disorders : Headache, somnolence, dizziness, insomnia, hyponatremic convulsions Psychiatric disorders : Confusional state* Respiratory, thoracic and mediastinal disorders : Nasal congestion, rhinitis, epistaxis, sore throat, cough, upper respiratory infections Skin and subcutaneous disorders : Pruritus Vascular disorders : Hypertension, hypotension, flushing *Reported in association with hyponatremia Adverse reactions that have been identified in patients administered STIMATE are headache, eye redness, tachycardia, flushing, nasal congestion, rhinitis, epistaxis, nausea and abdominal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .