FDA label a71ad66e-6d30-05fd-e053-2a95a90a992c

WARNING LASIX ® (furosemide) is a potent diuretic which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dose schedule must be adjusted to the individual patient’s needs ( s ee DOSAGE AND ADMINISTRATION ) .

WARNINGS In patients with hepatic cirrhosis and ascites, LASIX therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis. Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, LASIX should be discontinued. Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that LASIX ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4mg LASIX per minute has been used) ( s ee PRECAUTIONS: Drug Interactions ) .

ADVERSE REACTIONS Adverse reactions are categorized below by organ system and listed by decreasing severity. Gastrointestinal System Reactions 1. hepatic encephalopathy in patients with hepatocellular insufficiency 6. oral and gastric irritation 7. cramping 2. pancreatitis 8. diarrhea 3. jaundice (intrahepatic cholestatic jaundice) 9. constipation 4. increased liver enzymes 10. nausea 5. anorexia 11. vomiting Systemic Hypersensitivity Reactions 1. Severe anaphylactic or anaphylactoid reactions (e.g., with shock) 3. interstitial nephritis 4. necrotizing angiitis 2. systemic vasculitis Central Nervous System Reactions 1. tinnitus and hearing loss 5. headache 2. paresthesias 6. blurred vision 3. vertigo 7. xanthopsia 4. dizziness Hematologic Reactions 1. aplastic anemia 5. leukopenia 2. thrombocytopenia 6. anemia 3. agranulocytosis 7. eosinophilia 4. hemolytic anemia Dermatologic-Hypersensitivity Reactions 1. toxic epidermal necrolysis 7. bullous pemphigoid 2. Stevens-Johnson Syndrome 3. erythema multiforme 8. purpura 9. photosensitivity 4. drug rash with eosinophilia and systemic symptoms 10. rash 11. pruritis 5. acute generalized exanthematous pustulosis 6. exfoliative dermatitis 12. urticaria Cardiovascular Reaction 1. Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates, or narcotics. 2. Increase in cholesterol and triglyceride serum levels Other Reactions 1. hyperglycemia 6. restlessness 2. glycosuria 7. urinary bladder spasm 3. hyperuricemia 8. thrombophlebitis 4. muscle spasm 9. fever 5. weakness Whenever adverse reactions are moderate or severe, LASIX dosage should be reduced or therapy withdrawn. To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 (1-866-9VALIDUS) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

<table> <col width="319"/> <col width="48"/> <col width="271"/> <tbody> <tr> <td colspan="3" align="left"> <content styleCode="bold">Gastrointestinal System Reactions</content> </td> </tr> <tr> <td>1. hepatic encephalopathy in patients with hepatocellular insufficiency </td> <td colspan="2">6. oral and gastric irritation 7. cramping </td> </tr> <tr> <td>2. pancreatitis</td> <td colspan="2">8. diarrhea</td> </tr> <tr> <td>3. jaundice (intrahepatic cholestatic jaundice)</td> <td colspan="2">9. constipation</td> </tr> <tr> <td>4. increased liver enzymes</td> <td colspan="2">10. nausea</td> </tr> <tr> <td>5. anorexia</td> <td colspan="2">11. vomiting</td> </tr> <tr> <td/> <td colspan="2"/> </tr> <tr> <td colspan="3" align="left"> <content styleCode="bold">Systemic Hypersensitivity Reactions</content> </td> </tr> <tr> <td>1. Severe anaphylactic or anaphylactoid reactions (e.g., with shock)</td> <td colspan="2">3. interstitial nephritis 4. necrotizing angiitis </td> </tr> <tr> <td>2. systemic vasculitis</td> <td colspan="2"/> </tr> <tr> <td/> <td colspan="2"/> </tr> <tr> <td colspan="3" align="left"> <content styleCode="bold">Central Nervous System Reactions</content> </td> </tr> <tr> <td>1. tinnitus and hearing loss</td> <td colspan="2">5. headache</td> </tr> <tr> <td>2. paresthesias</td> <td colspan="2">6. blurred vision</td> </tr> <tr> <td>3. vertigo</td> <td colspan="2">7. xanthopsia</td> </tr> <tr> <td>4. dizziness</td> <td colspan="2"/> </tr> <tr> <td/> <td colspan="2"/> </tr> <tr> <td colspan="3" align="left"> <content styleCode="bold">Hematologic Reactions</content> </td> </tr> <tr> <td>1. aplastic anemia </td> <td colspan="2">5. leukopenia</td> </tr> <tr> <td>2. thrombocytopenia</td> <td colspan="2">6. anemia</td> </tr> <tr> <td>3. agranulocytosis </td> <td colspan="2">7. eosinophilia</td> </tr> <tr> <td>4. hemolytic anemia</td> <td colspan="2"/> </tr> <tr> <td/> <td colspan="2"/> </tr> <tr> <td colspan="3" align="left"> <content styleCode="bold">Dermatologic-Hypersensitivity Reactions</content> </td> </tr> <tr> <td>1. toxic epidermal necrolysis</td> <td colspan="2">7. bullous pemphigoid</td> </tr> <tr> <td>2. Stevens-Johnson Syndrome 3. erythema multiforme </td> <td colspan="2">8. purpura 9. photosensitivity </td> </tr> <tr> <td>4. drug rash with eosinophilia and systemic symptoms</td> <td colspan="2">10. rash 11. pruritis </td> </tr> <tr> <td>5. acute generalized exanthematous pustulosis 6. exfoliative dermatitis </td> <td colspan="2">12. urticaria</td> </tr> <tr> <td/> <td colspan="2"/> </tr> <tr> <td colspan="3" align="left"> <content styleCode="bold">Cardiovascular Reaction</content> </td> </tr> <tr> <td colspan="3">1. Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates, or narcotics.</td> </tr> <tr> <td colspan="2">2. Increase in cholesterol and triglyceride serum levels</td> <td/> </tr> <tr> <td colspan="2"/> <td/> </tr> <tr> <td colspan="3" align="left"> <content styleCode="bold">Other Reactions</content> </td> </tr> <tr> <td>1. hyperglycemia</td> <td colspan="2">6. restlessness</td> </tr> <tr> <td>2. glycosuria</td> <td colspan="2">7. urinary bladder spasm</td> </tr> <tr> <td>3. hyperuricemia</td> <td colspan="2">8. thrombophlebitis</td> </tr> <tr> <td>4. muscle spasm</td> <td colspan="2">9. fever</td> </tr> <tr> <td>5. weakness</td> <td colspan="2"/> </tr> </tbody> </table>