Ramipril is an ACE inhibitor that works similarly to captopril in terms of pharmacology and blocks the production of angiotensin II from angiotensin I.

• Heart failure post-myocardial infarction:

  • It is employed to treat heart failure (HF) following myocardial infarction (MI)

• Hypertension:

  • It is used in the treatment of hypertension

• Reduction of myocardial infarction, stroke, and death:

  • In individuals under the age of 55 who are at a high risk of experiencing serious cardiovascular events, it is used to lower the risk of MI, stroke, and mortality.

• Off Label Use Ramipril in Adults:

• Also used in :
  • Stable coronary artery disease
  • Non–ST-elevation acute coronary syndrome
  • ST-elevation acute coronary syndrome
  • Heart failure with reduced ejection fraction

Ramipril dose in Adults

• When starting ramipril, stop taking or lower the dosage of a concurrent diuretic.
• Reduce the initial ramipril dose if the diuretic cannot be stopped if the dose is too high.

Treatment of Heart failure post-myocardial infarction:

• 2.5 mg twice daily is the starting dose.
• For hypotension, it can be lowered to 1.25 mg twice daily.
• Continue the first dose for a week, then gradually increase it every three weeks as tolerated until you reach the desired amount of 5 mg twice daily.

Ttreatment of Hypertension:

• 2.5 mg are initially administered once daily.
• Titration is carried out based on the patient's response after two to four weeks, up to a maximum of 20 mg per day in one or two divided doses.

Treatment of reduction in risk of MI, stroke, and death from cardiovascular causes:

• The first dose is 2.5 mg once day for 1 week, followed by 5 mg once daily for the following 21 days. As tolerated, the dose is increased to the maintenance dose of 10 mg once daily.
• In patients with hypertension or who have just undergone a MI, it may be given in divided doses.

Off Label dosage:

• The target dose is 10 mg once daily
• The starting dose is 1.25 to 2.5 mg once daily.

• Dosage adjustment:

  • Titrate is initially administered
  • Once daily as tolerated until effect.

Dose in Childrens

Treatment of hypertension:

The recommended dose of ramipril for children is unknown. The typical dosage is 2.5 mg (5ml) once daily, though.

Ramipril Pregnancy Risk Factor: D

• Drugs that interfere with the renin-angiotensin systems can harm or kill a developing foetus.
• Once you are aware that you are pregnant, stop immediately.
• Ramipril crosses the placenta
• Oligohydramnios are often associated with drugs that affect the RAAS system.
• Oligohydramnios can cause fetal kidney dysfunction and skeletal malformations.
• These drugs can also cause skull hypoplasia and anuria in pregnancy.
• Although teratogenic side effects could arise from a mother taking an ACE inhibitor during the first trimester (although this finding could be confounded by maternal diseases)
• Exposure later in pregnancy can lead to adverse fetal outcomes. Therefore, pregnant women should not use ACE inhibitors.
• Testing for hypotension, hyperkalemia, and oliguria in children who were exposed to ACE drugs during pregnancy is necessary.
• After an irreversible fetal trauma, Oligohydramnios may not be apparent.
• Although data on the effectiveness of dialysis or exchange transfusions in neonates are limited, it is possible to reverse hypotension and improve renal function with dialysis or transfusions.
• Side effects of chronic maternal hypertension can also be experienced by the mother and the baby.
• Women of reproductive age should not be given ACE inhibitors.
• Other agents should be considered if treatment is needed for hypertension and chronic heart failure during pregnancy.

Ramipril use during breastfeeding:

• After a single oral dose (10 mg), Ramipril or its metabolites weren't found in breast milk.
• It is unknown if multiple doses can produce detectable levels.
• The manufacturer does not recommend breastfeeding.

Ramipril dose in Kidney disease:

• CrCl >40 mL/minute:

  • No dosage adjustment required.

• CrCl <40 mL/minute:

  • Give 25% of normal dose.

• Heart failure post-MI:

  • Initially, 1.25 mg once daily is prescribed.
  • If tolerated, it may be raised to 1.25 mg twice daily, and eventually up to 2.5 mg twice daily.

• Hypertension:

  • Initial dosage is 1.25 mg once daily, increasing as tolerated until desired effect is achieved.
    The daily dose cap is set at 5 mg.

• Renal artery stenosis:

  • Initially, 1.25 mg is given once daily
  • titrate as tolerated to effect.

Dose in Liver disease:

• The manufacturer's labelling does not mention dosage modifications.
• Ramipril plasma levels can become noticeably increased in patients with hepatic impairment.

• Data from trials on hypertension and heart failure are included in the frequency ranges.
• Patients with heart failure have often been found to experience higher rates of adverse effects.
• In this demographic, however, there are also more harmful effects linked to placebos.

Common Side Effects of Ramipril Include:

• Cardiovascular:

  • Hypotension

• Respiratory:

  • Increased Cough

Less Common Side Effects of Ramipril Include:

• Cardiovascular:

  • Syncope
  • Orthostatic Hypotension
  • Angina Pectoris

• Central Nervous System:

  • Dizziness
  • Vertigo
  • Fatigue
  • Noncardiac Chest Pain
  • Headache

• Endocrine & Metabolic:

  • Hyperkalemia

• Gastrointestinal:

  • Vomiting
  • Nausea

• Renal:

  • Renal Insufficiency
  • Increased Serum Creatinine
  • Increased Blood Urea Nitrogen

• Respiratory:

  • Cough

Contraindication to Ramipril Include:

• Hereditary/idiopathic angioedema, hypersensitivity to ramipril, other ACE inhibitors, or any ingredient in the formulation
• History of angioedema associated with use of an ACE inhibitor in the past, concurrent use of aliskiren with diabetes patients, or within 36 hours after switching to or from sacubitril (a neprilysin inhibitor).
• Bilateral renal artery stenosis that is hemodynamically significant (or unilateral in one kidney)
• Use of aliskiren in conjunction with hypotensive and hemodynamically unstable conditions in patients with moderate to severe renal impairment (GFR 60 mL/minute/1.73 m), hyperkalemia (>5 mMol/L)
• End-organ damage from concurrent use of angiotensin II receptor blockers (ARBs) and hypotensive individuals with congestive heart failure in diabetic patients
• End-organ damage from concurrent use of angiotensin II receptor blockers (ARBs) and hypotensive individuals with congestive heart failure in diabetic patients
• combination with extracorporeal therapy that causes blood interaction with surfaces that are negatively charged (dialysis, hemofiltration with certain highflux membranes [eg, Polyacrylonitrile] and low-density lipoprotein Apheresis using dextran).
• Breastfeeding
• Pregnancy

Warnings and precautions

• Angioedema

  • Any time, but especially after the initial dose, angioedema can happen.
  • It could affect the intestines, neck, or head (possibly compromising the airway).
  • Patients of color, patients with idiopathic angioedema, or patients who have had angioedema as a result of ACE inhibitor therapy, are at greater risk.
  • The risk can be increased by using mTOR inhibitors (such as everolimus) and neprilysin inhibitors (such as sacubitril) together.
  • Frequent and prolonged monitoring may be necessary due to the possibility of airway obstruction. This is especially true if larynx, tongue, glottis or glottis are involved.
  • Patients who have had previous airway surgery are at greater risk for obstruction.
  • Patients with angioedema from ACE inhibitor therapy are strictly prohibited.

• Cholestatic jaundice

  • Cholestatic jaundice is a rare side effect of ACE inhibitors.
  • It may result in fulminant liver necrosis (some even fatal).
  • If you notice a marked increase in hepatic transaminases and jaundice, stop immediately.

• Cough:

  • Dry, ineffective, and hacking coughs are brought on by ACE inhibitors.
  • It typically happens during the first few months of therapy and should disappear after 1 to 4 weeks of stopping the ACE inhibitor.
  • Before stopping treatment, you should also take into account additional reasons of cough, such as lung congestion in patients with heart disease.

• Hematologic effects

  • It has been connected to anaemia, agranulocytosis, neutropenia, and myeloid hypoplasia.
  • Neutropenia is more likely in patients with significant renal impairment.
  • Neutropenia is more likely to occur in patients with renal impairment or collagen vascular disease (such as systemic lupus erythematosus).
  • In such patients, routinely do a differential CBC.

• Hyperkalemia:

  • Patients could get hyperkalemia.
  • Risk factors are
    • Renal impairment
    • Use of potassium-sparing diuretics in conjunction
    • Potassium-containing salts
    • Potassium supplements and/or
    • diabetes mellitus
  • Potassium should be continuously checked, and these substances should be taken with caution.

• Hypersensitivity reactions

  • With ACE inhibitors, anaphylactic/anaphylactoid responses could happen.
  • Hemodialysis (CVVHD, for example), high-flux dialysis membranes (AN69), and, incredibly infrequently, low density lipoprotein (low-density) apheresis employing dextran sulfatecellulose, can all cause severe allergic responses.
  • Patients who get ACE inhibitors and are exposed to Hymenoptera (bee or wasp) venom seldom experience significant allergic reactions.

• Hypotension/syncope

  • Hypotension may be symptomatic with or without syncope. This is usually the case after several doses.
  • These effects are most common in patients with low volume.
  • correct volume depletion before initiation
  • Particularly with the initial dose and subsequent dosing increases, close supervision of patients is important.
  • The rate of blood pressure reduction should be proportionate to the patient's medical condition.
  • Even while doses must be lowered in cases of hypotension, this is not a cause to stop using ACE inhibitors in the future.
  • This is especially true for heart disease patients, for whom a reduction in systolic pressure is preferred.

• Renal function deterioration:

  • It might be connected to a decline in renal function and/or a rise in serum creatinine.
  • Patients with poor renal flow (such as those with kidney artery stenosis or heart failure) who rely on angiotensin II-mediated efferent arterial vasoconstriction for their GFR are most likely to experience this.
  • Deterioration may lead to oliguria, acute renal failure, or progressive azotemia.
  • Small increases in serum creatinine may happen after starting.
  • Patients with significant and progressive deterioration of renal function should be considered for treatment.

• Aortic stenosis

  • Patients with severe aorticstenosis should be cautious. It may cause decreased coronary perfusion, which can lead to ischemia.

• Ascites:

  • Patients with ascites due cirrhosis, refractory or other causes should not be given this medication.
  • If patients with cirrhosis or ascites are unable to refrain from taking the medication, it is crucial to regularly monitor blood pressure and kidney function to stop the rapid onset of renal failure.

• Cardiovascular disease

  • Due to the repercussions of dropping blood pressure, patients with ischemic heart disease and cerebrovascular illnesses should be continuously watched (eg stroke, MI).
  • Blood pressure may be raised by fluid replacement. Then, therapy can start again.
  • Stop treating hypotension-recurring patients.

• Collagen vascular disease:

  • Patients with collagen vascular disease should exercise caution, especially if they also have kidney impairment.
  • Hematologic toxicity may be more likely to occur in these patients.

• Hepatic impairment

  • Patients with hepatic impairment shouldn't use ramipril because it is primarily processed by the liver.

• Hypertrophic cardiomyopathy (HCM)

  • Patients with HCM or outflow tract obstruction should be cautious. Reduced afterload could worsen the symptoms.

• Renal artery stenosis

  • Patients who have unilateral or bilateral renal artery stenosis that is untreated should exercise caution.
  • It should be avoided if unilateral and bilateral renal artery constriction without stenting is known or suspected.

• Renal impairment

  • Patients with impaired renal function should be cautious. Dosage adjustment may be necessary.
  • Do not increase the dose too quickly as this could cause further renal impairment.

Ramipril: Drug Interaction

Monitor:

• Blood pressure
• Serum creatinine
• BUN
• Potassium
• Monitor the patient's CBC with differential on a regular basis if they have collagen vascular disease or renal impairment.
• Monitor heart failure patients who have recently experienced a myocardial infarction for at least 2 hours after the initial dose and for at least another hour after the blood pressure has normalised.

How to administer Ramipril?

• Swallow capsule as a whole
• Open it, and combine the contents with 120 mL of water, apple juice, or applesauce.

Mechanism of action:

• Ramipril, an ACE inhibitor, is similar to captopril in its pharmacologic properties and blocks the production of angiotensin II from angiotensin I.
• Ramipril undergoes enzymatic saponification by esterases in the liver to produce ramiprilat, which is ramipril's physiologically active metabolite.
• The competitive, high-affinity, and reversible binding of ramiprilat to the angiotensin-converting enzyme causes ramipril to have pharmacological effects by inhibiting the production of the potent vasoconstrictor angiotensin II.
• A slow rate of dissociation gives this isomerized enzyme inhibitor complex its high potency, prolonged duration of action, and high potency.
• Angiotensin II, which raises the CNS's adrenergic output, also lowers blood pressure via a CNS mechanism.
• ACE inhibitors may decrease the conversion of vasoactive kallikreins to active hormones, lowering blood pressure.

The onset of action:

• 1-2 hours

Duration:

• 24 hours

Absorption:

• Well absorbed (50% to 60%)

Distribution:

• a triphasic decrease in plasma levels
• A distribution phase to the peripheral compartment, plasma protein, and tissue ACE is the rapid fall. (2–4 hour half-life)
• The apparent elimination phase of the second phase displays the clearance of free ramiprilat (half-life: 9-18 hours)
• The terminal elimination phase, which represents the phase of balance between tissue binding and dissociation, is the last phase.

Protein binding:

• Ramipril: 73%; Ramiprilat: 56%

Metabolism:

• Hepatic to the active form, ramiprilat

Bioavailability:

• Ramipril: 28%; Ramiprilat: 44%

Half-life elimination:

• Ramiprilat: Effective: 13-17 hours; Terminal: >50 hours

Time to peak, serum:

• Ramipril: ~1 hour; Ramiprilat: 2-4 hours

Excretion:

• Via Urine (60%) and feces (40%) as parent drug and metabolite 

International Brands of Ramipril:

• Altace
• ACT Ramipril
• AG-Ramipril
• Altace
• APO-Ramipril
• Auro-Ramipril
• DOM-Ramipril
• JAMP-Ramipril
• Mar-Ramipril
• MINT-Ramipril
• MYLAN-Ramipril
• Pharma-Ramipril
• PMS-Ramipril
• PRIVARamipril
• PRO-Ramipril-1.25
• PRO-Ramipril-10
• PRO-Ramipril-2.5
• PRO-Ramipril-5
• Ramace
• Ramipril-10
• Ramipril-2.5
• Ramipril-5
• RAN-Ramipril
• SANDOZ Ramipril
• TEVARamipril
• VAN-Ramipril
• Acovil
• Acuril
• Altace
• Amipril
• Ampril
• Anexia
• Anhiram
• Bigastus
• Cardace
• Cardika
• Cardipril
• Cartace
• Corpril
• Decapril
• Delix
• Hartil
• Heartprilprotect
• Hyperil
• Hypren
• Intemipril
• Lostapres
• Naprix
• Normopril
• Piramil
• Polapril
• Pramace
• Pril
• Prilace
• Primace
• Prohytens
• Quark
• Ramace
• Ramey
• Ramicard
• Ramicor
• Ramily
• Ramipres
• Ramiprin
• Ramipro
• Ramitace
• Ramitens
• Ramixal
• Rampil
• Ramtace
• Redutens
• Servace
• Sipo
• Syntace
• Topril
• Triatec
• Triateckit
• Triltec
• Tripril
• Tritace
• Tritace Protect
• Tryzan
• Unipril
• Vaspril
• Vesdil
• Zenra

Ramipril brands in Pakistan: