Bell-Kenz Pharma


Euro Generics
Full Prescribing Info
Each film-coated tablet contains Ramipril 5 mg.
Pharmacology: Ramipril (Amivan) is an angiotensin converting enzyme (ACE) inhibitor, which after hydrolysis to ramiprilat, blocks the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. So, inhibition of ACE by Ramipril results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and decreased aldosterone secretion. Thus, Ramipril exerts its antihypertensive activity.
Pharmacokinetics: Ramipril acts as a prodrug of the diacid ramiprilat, its active metabolite. After oral doses at least 50 to 60% is absorbed. Ramipril is metabolized in the liver to ramiprilat; other metabolites are inactive. Peak plasma concentrations of ramiprilat are achieved 2 to 4 hours after an oral dose of ramipril. Ramiprilat is about 56% bound to plasma proteins. After oral doses ramipril is excreted primarily in the urine, as ramiprilat, other metabolites, and some unchanged drug. About 40% of an oral dose appears in the faeces; this may represent both biliary excretion and unabsorbed drug. The effective half-life for accumulation of ramiprilat is 13 to 17 hours after multiple doses of ramipril 5 to 10 mg, but is much longer for doses of 1.25 to 2.5 mg daily; the difference relates to the long terminal half-life associated with saturable binding to the angiotensin-converting enzyme. The clearance of ramiprilat is reduced in renal impairment.
Mild to severe hypertension, where it may be used alone or in combination with thiazide diuretics.
Congestive Heart failure.
To reduce the risk of stroke, myocardial infarction and death from cardiovascular events in patients with history of cardiovascular diseases.
Dosage/Direction for Use
Hypertension: For the management of hypertension in adults not receiving a diuretic, the usual initial dose of Ramipril is 1.25-2.5 mg once daily. Dosage generally is adjusted no more rapidly than at 2-week intervals. The usual maintenance dosage in adults is 2.5-20 mg daily given as a single dose or in 2 divided doses daily. If blood pressure (BP) is not controlled with Ramipril alone, a diuretic may be added.
Congestive Heart failure after myocardial infarction: In this case, Ramipril therapy may be initiated as early as 2 days after myocardial infarction. An initial dose 2.5 mg twice daily is recommended, but if hypotension occurs, dose should be reduced to 1.25 mg twice daily. Therapy is then titrated to a target daily dose of 5 mg twice daily, with dosage increasing being about 3 weeks apart.
Prevention of major cardiovascular events: In this case, the recommended dose is 2.5 mg once daily for the first week of therapy and 5 mg once daily for the following weeks; dosage then may be increased, as tolerated, to a maintenance dosage of 10 mg once daily.
Dosage in Renal impairment: For the patient with hypertension and renal impairment, the recommended initial dose is 1.25 mg Ramipril once daily. Subsequent dosage should be titrated according to individual tolerance and blood pressure response, up to a maximum of 5 mg daily. For the patients with heart failure and renal impairment, the recommended dose is 1.25 mg once daily. The dose may be increased to 1.25 mg twice daily and up to maximum dose of 2.5 mg twice daily depending upon clinical response and tolerability.
In patients with creatinine clearance <40 mL/min/1.73 m2 (serum creatinine approximately >2.5 mg/dL) doses only 25% of those normally used should be expected to induce full therapeutic levels of ramiprilat.
Limited data on human overdosage are available. The most likely clinical manifestations would be symptoms attributable to hypotension. Because the hypotensive effect of Ramipril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat Ramipril overdosage by infusion of normal saline solution.
Ramipril is contraindicated in patients who are hypersensitive to any component of this product and in patients with history of angio-edema related to previous treatment with ACE inhibitor.
Special Precautions
The following may occur: anaphylactoid and possibly related reactions, head and neck angioedema, intestinal angioedema, hypotension, hepatic failure, neutropenia/agranulocytosis, hematological reactions in patients with collagen vascular disease (e.g. systemic lupus erythematosus, scleroderma) and renal impairment. Monitoring of white blood cell counts should be considered in patients with collagen vascular disease, especially if the disease is associated with impaired renal function.
Hyperkalemia: Concomitant administration with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium.
Hypotension: In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of ramipril. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy. Then, if blood pressure is not controlled with ramipril alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 1.25 mg should be used to avoid excess hypotension.
Impaired Renal Function: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin angiotensin-aldosterone system, treatment with angiotensin converting enzyme inhibitors, including this drug, may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur. Experience with another angiotensin converting enzyme inhibitor suggests that these increases are usually reversible upon discontinuation of this drug and/or diuretic therapy. In such patients renal function should be monitored during the first few weeks of therapy. Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when this drug has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of this drug and/or discontinuation of the diuretic may be required. Evaluation of the hypertensive patient should always include assessment of renal function.
Cough: Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
Impaired Liver Function: Since ramipril is primarily metabolized by hepatic esterases to its active moiety, ramiprilat, patients with impaired liver function could develop markedly elevated plasma levels of ramipril. However, since the renin-angiotensin system may be activated in patients with severe liver cirrhosis and/or ascites, particular caution should be exercised in treating these patients.
Surgery/Anesthesia: In patients undergoing surgery or during anesthesia with agents that produce hypotension, ramipril may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.
Fetal Toxicity: 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 as soon as possible.
These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observed infants with histories of in uteroexposure to this drug for hypotension, oliguria, and hyperkalemia. No teratogenic effects of ramipril were seen in studies of pregnant rats, rabbits, and cynomolgus monkeys. On a body surface area basis, the doses used were up to approximately 400 times (in rats and monkeys) and 2 times (in rabbits) the recommended human dose.
Use in Elderly: One pharmacokinetic study conducted in hospitalized elderly patients indicated that peak ramiprilat levels and area under the plasma concentration time curve (AUC) for ramiprilat are higher in older patients.
Adverse Reactions
Body As a Whole: Anaphylactoid reactions.
Cardiovascular: Symptomatic hypotension (reported in 0.5% of patients in US trials), syncope and palpitations.
Respiratory: Cough.
Hematologic: Pancytopenia, hemolytic anemia and thrombocytopenia.
Renal: Some hypertensive patients with no apparent pre-existing renal disease have developed minor, usually transient, increases in blood urea nitrogen and serum creatinine, acute renal failure.
Angioneurotic Edema: Angioneurotic edema.
Gastrointestinal: Hepatic failure, hepatitis, jaundice, pancreatitis, abdominal pain (sometimes with enzyme changes suggesting pancreatitis), anorexia, constipation, diarrhea, dry mouth, dyspepsia, dysphagia, gastroenteritis, increased salivation and taste disturbance, nausea and vomiting.
Dermatologic: Apparent hypersensitivity reactions (manifested by urticarial, pruritus, or rash, with or without fever), photosensitivity, purpura, onycholysis, pemphigus, pemphigoid, erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome.
Neurologic and Psychiatric: Anxiety, amnesia, convulsions, depression, hearing loss, insomnia, nervousness, neuralgia, neuropathy, paresthesia, somnolence, tinnitus, tremor, vertigo, and vision disturbances, dizziness, headache.
Miscellaneous: As with other ACE inhibitors, a symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, photosensitivity, rash and other dermatologic manifestations.
Other: Arthralgia, arthritis, dyspnea, edema, epistaxis, impotence, increased sweating, malaise, myalgia, and weight gain.
Post-Marketing Experience: There have been rare reports of hypoglycemia reported during therapy when given to patients concomitantly taking oral hypoglycemic agents or insulin. The causal relationship is unknown.
Drug Interactions
Concomitant administration with diuretics may lead to serious hypotension and in addition dangerous hyperkalemia with potassium sparing diuretics. Concomitant therapy with Lithium may increase the serum Lithium concentration. NSAIDs may reduce the antihypertensive effect of Ramipril and cause deterioration of renal function.
Store at temperatures not exceeding 30°C. Protect from light.
MIMS Class
ACE Inhibitors/Direct Renin Inhibitors
ATC Classification
C09AA05 - ramipril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.
Amivan FC tab 5 mg
30's (P405/film-coated tab)
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