Ramipril

1 INDICATIONS AND USAGE Ramipril capsules are an angiotensin converting enzyme (ACE) inhibitor indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. It may be used alone or in combination with thiazide diuretics ( 1.1 ). In patients 55 years or older at high risk of developing a major cardiovascular event, ramipril capsules are indicated to reduce the risk of myocardial infarction, stroke, or death from cardiovascular causes ( 1.2 ). Ramipril capsules are indicated in stable patients who have demonstrated clinical signs of congestive heart failure post-myocardial infarction ( 1.3 ).

6 ADVERSE REACTIONS The most common adverse reactions in patients with hypertension included headache, dizziness, fatigue, and cough ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the 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. Hypertension Ramipril has been evaluated for safety in over 4000 patients with hypertension; of these, 1230 patients were studied in U.S. controlled trials, and 1107 were studied in foreign controlled trials.

8.1 Pregnancy Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ramipril as soon as possible.

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue ramipril as soon as possible [see Warnings and Precautions (5.6) ]. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.6) ] . WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning When pregnancy is detected, discontinue ramipril as soon as possible (5.6) . 5 WARNINGS AND PRECAUTIONS Angioedema, increased risk in patients with a prior history (5.1) Hypotension and hyperkalemia (5.5, 5.8) Renal impairment: monitor renal function during therapy (5.3) Avoid concomitant use of an ACE inhibitor and angiotensin blocker (5.7) Rare cholestatic jaundice and hepatic failure (5.2) Rare neutropenia and agranulocytosis (5.4) 5.1 Anaphylactoid and Possibly Related Reactions Presumably because drugs that act directly on the renin-angiotensin-aldosterone system (e.g., ACE inhibitors) affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving these drugs (including ramipril) may be subject to a variety of adverse reactions, some of them serious. 4 CONTRAINDICATIONS Ramipril capsules are contraindicated in patients who are hypersensitive to this product or any other ACE inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor). Ramipril capsules are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril).