DESMODA

5 WARNINGS AND PRECAUTIONS 5.1 Hyponatremia 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 postmarketing experience in patients treated with desmopressin acetate. Unless properly diagnosed and treated hyponatremia can be fatal. Observe all patients receiving DESMODA for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of 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. In order to decrease the risk of water intoxication with hyponatremia, fluid restriction is recommended. Careful fluid intake 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 [see Drug Interactions (7.1)]. Temporarily stop treatment with DESMODA during acute intercurrent illness characterized by fluid and/or electrolyte imbalance (e.g., systemic infections, fever, recurrent vomiting or diarrhea) or under conditions of extremely hot weather, vigorous exercise or other conditions associated with increased water intake. 5.2 Fluid Retention Desmopressin acetate can cause fluid retention, which can worsen underlying conditions that are susceptible to volume status. Closely monitor patients with heart failure or uncontrolled hypertension. DESMODA is not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention. 5.3 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis have been reported with intravenous and nasal administration of desmopressin acetate, including cases of fatal anaphylaxis with intravenous desmopressin acetate [see Adverse Reactions (6)]. DESMODA is contraindicated in patients with a history of hypersensitivity to desmopressin acetate or any of the inactive ingredients of DESMODA [see Contraindications (4)]. If signs or symptoms of hypersensitivity reactions occur, discontinue DESMODA and initiate appropriate supportive care. 5.4 Risk of Benzyl Alcohol Toxicity in Neonates DESMODA contains 2.74 mg/mL of benzoic acid, a metabolite of benzyl alcohol. Serious adverse reactions of metabolic acidosis, including fatalities, have been reported in low-birth-weight neonates (less than 2,500 grams) and preterm neonates (gestational age less than 34 weeks) who received benzyl alcohol-containing drugs intravenously. The relationship between systemic levels of benzoic acid and toxicity is not well-characterized [see Use in Specific Populations (8.4)]. Use DESMODA with caution in low-birth-weight neonates or preterm neonates and monitor for signs and symptoms of metabolic acidosis. • Hyponatremia: Excessive fluid intake when urine output is limited by the antidiuretic effect of desmopressin may lead to water intoxication with hyponatremia. Fluid restriction is recommended. (5.1) • Fluid Retention: Desmopressin acetate may cause fluid retention. Use with caution in patients with heart failure or uncontrolled hypertension. DESMODA is not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention. (5.2) • Hypersensitivity: Severe reactions have occurred. Monitor for reactions during administration and interrupt if reaction occurs. (5.3)

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: •Hyponatremia [see Warnings and Precautions (5.1)] •Fluid Retention [see Warnings and Precautions (5.2)] •Hypersensitivity [see Warnings and Precautions (5.3)] •Risk of Benzyl Alcohol Toxicity in Neonates [see Warnings and Precautions (5.4)] The following adverse reactions associated with the use of desmopressin acetate were identified in clinical studies or postmarketing reports. Because some of these reactions were 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: hypertension Gastrointestinal disorders: nausea, vomiting, diarrhea, constipation, abdominal cramps General disorders: headache, malaise, drug ineffective, edema, fatigue Hepatobiliary disorders: transient increases in AST (1.5 times the upper limit of normal) Immune system disorders: severe allergic reactions, anaphylaxis has occurred with other formulations of desmopressin Metabolism and nutrition: dehydration, hyponatremia, water intoxication with hyponatremia Nervous system disorders: hyponatremic convulsions, hyponatremic convulsions associated with concomitant use of the following medications: oxybutynin and imipramine [see Drug Interactions (7.1)], asthenia, coma, disturbance in attention, psychomotor hyperactivity, dizziness, somnolence, depressed level of consciousness, falls. Psychiatric disorders: confusional state, abnormal behavior, emotional disorder, depression, hallucination, insomnia Renal and urinary disorders: bladder and urethral symptoms, including urinary retention, urine flow decreased, dysuria Skin and subcutaneous tissue disorders: rash, dermatitis allergic, sweating, flushing, urticaria Respiratory, thoracic and mediastinal disorders: dyspnea, epistaxis In long-term clinical studies in which patients with diabetes insipidus were followed for periods up to 44 months of desmopressin acetate oral therapy, transient increases in AST (SGOT) no higher than 1.5 times the upper limit of normal were occasionally observed. Elevated AST (SGOT) returned to the normal range despite the continued use of desmopressin acetate oral therapy. Most common adverse reactions include: headache, dizziness, nausea, abdominal pain, hypertension, and diarrhea. (6) To report SUSPECTED ADVERSE REACTIONS, contact Eton Pharmaceuticals, Inc. at 1-855-224-0233 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.