Ramipril
Classification
ACE inhibitor, antihypertensive
Indications
CCP: NSTEMI/STEMI
CCP: HFrEF post MI (heart failure with reduced ejection fraction; EF ≤ 40%)
CCP: Hypertension
Contraindications
- Hypersensitivity
- Hereditary/idiopathic angioedema
- Concomitant use with aliskiren in patients with diabetes mellitus
- Concomitant use or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).
- Hemodynamically relevant bilateral renal artery stenosis or unilateral in the single kidney
- Hypotensive or hemodynamically unstable states
- Hyperkalemia (>5 mmol/L)
- Congestive heart failure who are hypotensive.
- Concomitant use with angiotensin II receptor blockers (ARBs) in patients with diabetes end organ damage
- Moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2)
- Pregnancy, breastfeeding.
Cautions
- Use with caution in patients with hepatic impairment.
- Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction.
Adult dosages
CCP: NSTEMI/STEMI
- 2.5 mg od PO titrate up slowly based on response up to 20 mg/day
CCP: HFrEF
- 1.25 to 2.5 mg once daily; as tolerated, may increase every 1 to 2 weeks to a target dose of 10 mg once daily.
CCP: Hypertension
- 2.5 mg once daily; evaluate response every 2 to 4 weeks and titrate dose as needed up to 20 mg/day in 1 or 2 divided doses.
Pediatric Considerations And Dosing
- Dosing is unavailable or not applicable for this medication.
Mechanism Of Action
Ramipril is an ACE (Angiotensin Converting Enzyme) inhibitor which prevents the formation of angiotensin II from angiotensin I. The pharmacodynamic effects of Ramipril result from the high-affinity, competitive, reversible binding of ramiprilat (the active metabolite) to angiotensin-converting enzyme, thus preventing the formation of the potent vasoconstrictor angiotensin II.
Pharmacokinetics
Onset: 1-2 hours
Duration: 24 hours
Time to peak: 1 hour
Half-life: 13-17 hours
Adverse Effects
Cardiovascular:
- Hypotension
- Angina pectoris, orthostatic hypotension, syncope
Immunologic
- Anaphylactoid, angioedema, SJS
Respiratory:
- Increased cough
Central nervous system:
- Headache, dizziness, fatigue, vertigo, noncardiac chest pain
Endocrine & metabolic:
- Hyperkalemia
Gastrointestinal:
- Nausea, vomiting
Renal:
- Increased blood urea nitrogen (transient increases may occur more frequently), increased serum creatinine (transient increases may occur more frequently), renal insufficiency
Warning And Precautions
- Angioedema: At any time during treatment (especially following first dose), angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain).
- A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis.
- An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor.
- Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia.
- Hyperkalemia may occur with ACE inhibitors. Risk factors include renal impairment, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts.
- Deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II.
- Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus.
- The use in patients breastfeeding is not recommended by the manufacturer.
Drug Interactions
- Alfuzosin
- Aliskiren
- Allopurinol
- Alteplase
- Amifostine
- Amphetamines
- Angiotensin II
- Angiotensin II Receptor Blockers
- Antipsychotic Agents (Second Generation [Atypical])
- Aprotinin
- AzaTHIOprine
- Barbiturates
- Benperidol
- Brigatinib
- Brimonidine (Topical)
- Bromperidol
- Dapoxetine
- Dexmethylphenidate
- Diazoxide
- Dipeptidyl Peptidase-IV Inhibitors
- Drospirenone
- DULoxetine
- Eplerenone
- Everolimus
- Ferric Gluconate
- Ferric Hydroxide Polymaltose Complex
- Finerenone
- Gelatin (Succinylated)
- Gold Sodium Thiomalate
- Grass Pollen Allergen Extract (5 Grass Extract)
- Heparin
- Heparins (Low Molecular Weight)
- Herbal Products with Blood Pressure Increasing Effects
- Herbal Products with Blood Pressure Lowering Effects
- Hypotension-Associated Agents
- Icatibant
- Iron Dextran Complex
- Lanthanum
- Levodopa-Containing Products
- Lithium
- Loop Diuretics
- Lormetazepam
- Methylphenidate
- Molsidomine
- Naftopidil
- Nicergoline
- Nicorandil
- Nitroprusside
- Nonsteroidal Anti-Inflammatory Agents
- Nonsteroidal Anti-Inflammatory Agents (Topical)
- Obinutuzumab
- Pentoxifylline
- Pholcodine
- Phosphodiesterase 5 Inhibitors
- Potassium Salts
- Potassium-Sparing Diuretics
- Pregabalin
- Prostacyclin Analogues
- Quinagolide
- Racecadotril
- Ranolazine
- Sacubitril
- Salicylates
- Sirolimus
- Sodium Phosphates
- Tacrolimus (Systemic)
- Telmisartan
- Temsirolimus
- Thiazide and Thiazide-Like Diuretics
- TiZANidine
- Tolvaptan
- Trimethoprim
- Urapidil
- Urokinase