Ramace (Ramipril): An Angiotensin Converting Enzyme (ACE) Inhibitor

Ramace contains Ramipril, an angiotensin converting enzyme (ACE) inhibitor. It is indicated for the treatment of hypertension, congestive heart failure, and to reduce the risk of major cardiovascular events in high-risk patients. It belongs to the therapeutic class of Angiotensin-converting enzyme (ACE) inhibitors.

How Ramace Works (Pharmacology)

Ramipril exerts its effects by:

• Blocking ACE: After being hydrolyzed to its active metabolite, ramiprilat, it blocks the angiotensin converting enzyme (ACE). ACE is responsible for converting angiotensin I to angiotensin II.
• Decreased Angiotensin II: Inhibition of ACE by ramipril leads to decreased plasma angiotensin II levels. Angiotensin II is a potent vasoconstrictor and also stimulates aldosterone secretion.
• Vasodilation and Reduced Aldosterone: Reduced angiotensin II results in decreased vasopressor activity (vasodilation) and decreased aldosterone secretion.
• Antihypertensive Activity: These actions contribute to the antihypertensive effect of ramipril.
• Benefits in Heart Failure and Cardiovascular Risk Reduction: Its effects on the renin-angiotensin-aldosterone system also make it effective in managing heart failure and reducing the risk of stroke, myocardial infarction, and cardiovascular death.
• Long-acting and well-tolerated: Suitable for long-term therapy.

Key Indications & Benefits

Ramace is indicated for:

• Hypertension: To lower blood pressure, either as single-drug therapy or in combination with other antihypertensive agents.
• Congestive heart failure: Also used in combination with diuretics.
• Treatment of patients after acute myocardial infarction who have demonstrated clinical signs of congestive heart failure.
• Treatment of non-diabetic or diabetic overt glomerular or incipient nephropathy (kidney disease).
• Reduction in the risk of myocardial infarction, stroke, or cardiovascular death in patients with an increased cardiovascular risk, such as those with:
  • Manifest coronary heart disease (with or without a history of myocardial infarction).
  • A history of stroke.
  • A history of peripheral vascular disease.
  • Diabetes mellitus accompanied by at least one other cardiovascular risk factor (e.g., microalbuminuria, hypertension, elevated total cholesterol, low HDL cholesterol, smoking).

Dosage & Administration

Dosage of Ramipril must be adjusted according to patient tolerance and response. Tablets should be swallowed whole with sufficient liquid and can be taken before, during, or after a meal. Always consult a registered physician for specific dosage instructions.

Hypertension:

• Adults (not receiving a diuretic): Usual initial dose is 1.25-2.5 mg once daily.
• Dosage adjusted no more rapidly than at 2-week intervals.
• Usual maintenance dosage: 2.5-20 mg daily, as a single dose or in 2 divided doses.
• If BP is not controlled with Ramipril alone, a diuretic may be added.

Congestive Heart Failure after Myocardial Infarction:

• Therapy may be initiated as early as 2 days after myocardial infarction.
• Initial dose: 2.5 mg twice daily.
• If hypotension occurs, reduce dose to 1.25 mg twice daily.
• Titrate to a target daily dose of 5 mg twice daily.

Prevention of Major Cardiovascular Events:

• Recommended dose: 2.5 mg once daily for the first week, then 5 mg once daily for the following 3 weeks.
• Dosage may then be increased, as tolerated, to a maintenance dosage of 10 mg once daily.

Dosage in Renal Impairment:

• For hypertension and renal impairment: Recommended initial dose is 1.25 mg once daily. Max 5 mg daily.
• For heart failure and renal impairment: Recommended dose is 1.25 mg once daily. May increase to 1.25 mg twice daily and up to a maximum of 2.5 mg twice daily depending on response.
• Creatinine clearance 50-20 ml/min/1.73m$^2$: Initial daily dose generally 1.25 mg. Max 5 mg daily.

Important Considerations & Warnings

It is crucial to discuss your full medical history with your doctor before taking Ramace.

Contraindications:

• Hypersensitivity to ramipril, any other ACE inhibitor, or any excipients.
• History of angioedema.
• Concomitant use with sacubitril/valsartan therapy. Do not initiate Ramipril until sacubitril/valsartan is eliminated from the body, and vice versa (allow sufficient washout period).
• Hemodynamically relevant renal artery stenosis (bilateral or unilateral in a single kidney).
• Hypotensive or hemodynamically unstable states.
• Concomitant use with aliskiren-containing medicines in patients with diabetes or moderate to severe renal impairment (creatinine clearance <60 ml/min).
• Concomitant use with angiotensin II receptor antagonists (AIIRAs) in patients with diabetic nephropathy.
• During pregnancy.
• Concomitant use with extracorporeal treatments involving contact of blood with negatively charged surfaces (e.g., certain high-flux dialysis/hemofiltration membranes, low-density lipoprotein apheresis with dextran sulfate) due to risk of severe anaphylactoid reactions.

Side Effects:

• Generally well tolerated.
• Commonly reported: Dizziness, headache, fatigue, asthenia (weakness).
• Less frequently: Symptomatic hypotension, cough (a common ACE inhibitor side effect), nausea, vomiting, diarrhea, rash, urticaria, oliguria (reduced urine output), anxiety, amnesia.
• Rarely reported: Angioneurotic edema (swelling, potentially severe), anaphylactic reactions, and hyperkalemia (high potassium levels).

Pregnancy & Lactation:

• Pregnancy:Must not be taken during pregnancy. Pregnancy must be excluded before starting treatment, and avoided if ACE inhibitor treatment is indispensable. If pregnancy occurs, switch to a non-ACE inhibitor regimen as soon as possible due to risk of harm to the fetus.
• Lactation:Not recommended during breastfeeding.

Precautions & Warnings:

• Impaired Renal Function: Use with caution.
• Hyperkalemia: Use with caution, especially with other agents that can increase potassium.
• Hypotension: Use with caution, especially during initial dosing, in volume-depleted patients, or those with severe hypertension or conditions where a hypotensive reaction would be a particular risk (e.g., coronary or cerebral vessel stenoses).
• Impaired Hepatic Function: Use with caution. Treatment should be initiated only under close medical supervision. Maximum permitted daily dose is 2.5 mg in such cases.
• Fluid or Salt Depletion: In patients with incompletely corrected fluid or salt depletion, a reduced initial dose of 1.25 mg daily must be considered.
• Diuretic Pretreatment: Consider discontinuing the diuretic for at least 2-3 days or longer before starting Ramace, or reducing the diuretic dose. Initial daily dose generally 1.25 mg.

Drug Interactions:

• Diuretics: Concomitant administration may lead to serious hypotension and dangerous hyperkalemia with potassium-sparing diuretics.
• Lithium: Concomitant therapy may increase serum lithium concentration, leading to lithium toxicity.
• Alcohol: May exacerbate the reduction in BP, affecting ability to drive and operate machinery.
• NSAIDs (Non-Steroidal Anti-inflammatory Drugs): May reduce the antihypertensive effect of Ramace and cause deterioration of renal function.
• Sacubitril/Valsartan, Aliskiren, AIIRAs: See contraindications above for specific restrictions due to increased risk of angioedema, hypotension, hyperkalemia, and renal impairment.

Overdose Effects

• Signs and Symptoms: Excessive peripheral vasodilation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure.
• Management:
  • Primary detoxification: Gastric lavage, administration of adsorbents (e.g., activated charcoal), sodium sulfate (if possible within the first 30 minutes).
  • For hypotension: Consider administration of α1​-adrenergic agonists (e.g., norepinephrine, dopamine) or angiotensin II (angiotensinamide), in addition to volume and salt substitution.

Storage Conditions

Store at 30°C or below, protected from light. Keep out of the reach of children. Do not use later than the expiry date. To be dispensed only on the prescription of a registered physician.