Perindopril is an angiotensin-converting enzyme (ACE) inhibitor, a type of medication commonly used to treat high blood pressure (hypertension) and other cardiovascular conditions.

An inhibitor of the Angiotensin-Converting Enzyme (ACE), perindopril (Coversyl). Patients with hypertension are the target audience for this medication. Additionally, it is employed in the treatment of IHD, heart failure, and to lessen proteinuria.

Indications of Perindopril:

• Hypertension:
  • It is indicated for the managing high blood pressure.
• Guidelines:
  • In the absence of comorbidities (such as cerebrovascular disease, chronic kidney disease, diabetes, heart failure, or ischemic heart disease), monotherapy with calcium channel blockers and thiazide diuretics is preferred due to improved cardiovascular outcomes, according to the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.
  • ARBs and ACE inhibitors are also suitable for monotherapy. In individuals at high risk, such as those with stage 2 hypertension or an atherosclerotic cardiovascular disease [ASCVD] risk of 10% or greater, combination therapy is preferred.
• Stable coronary artery disease:
  • In patients with stable coronary artery disease, it is used to lower the risk of myocardial infarction or cardiovascular mortality.
• Guideline:
  • According to the American College of Cardiology/American Heart Association guidelines, unless contraindicated, all patients with stable ischemic heart disease who also have HTN, DM, LVEF 40%, or CKD should be administered an ACE inhibitor or ARB.
• Use: Off-Label: Adult
  • ST-elevation acute coronary syndrome
  • Non–ST-elevation acute coronary syndrome
  • Heart failure

Perindopril dose in adults:

Perindopril (Coversyl) dose in the treatment  of Heart failure (off-label):

• Start with a low dose of 2 milligrams, taken by mouth, once a day.
• Over time, the doctor may slowly increase the dose.
• The goal is to reach a dose between 8 to 16 milligrams, taken by mouth, once a day.

This dosing approach is based on guidelines from the American College of Cardiology and the American Heart Association. It's important to follow your doctor's instructions carefully when taking Perindopril for heart failure, even if the dose seems low at first.

Perindopril (Coversyl) dose in the treatment of Hypertension:

For High Blood Pressure:

• Starting Dose: Take 4 milligrams of Perindopril by mouth once a day.
• If needed, your doctor might increase the dose to make it more effective. The dose could go up to 16 milligrams once a day.
• The highest dose you should take is 16 milligrams in a day.

If You're Also Taking Water Pills (Diuretics):

• If possible, stop taking the water pill or take a lower dose before starting Perindopril. This helps to avoid a big drop in blood pressure.
• If you can't stop or decrease the water pill, keep a close eye on your blood pressure for the first few hours after you start taking Perindopril. After taking Perindopril, monitor your blood pressure for at least 2 hours and then make sure it's stable for another hour.

Perindopril (Coversyl) dose in the treatment:

• Starting Dose: Take 4 milligrams of Perindopril by mouth every day for 2 weeks.
• After 2 weeks, if you're feeling okay with the medication, the doctor might increase your dose to 8 milligrams once a day.

Perindopril (Coversyl) dose in Childrens

Not recommended for use in children.

Pregnancy Risk Category: D

[US Boxed Warning]

• Medications that affect the renin-angiotensin system, like ACE inhibitors, can harm or even cause the death of an unborn baby.
• If a woman becomes pregnant while taking these drugs, she should stop them immediately.
• These drugs can lead to serious complications for the baby, like lung and bone issues, and can even be fatal.
• Some effects can happen if the mother takes these drugs early in pregnancy.
• Pregnant women shouldn't take ACE inhibitors.
• If a baby was exposed to these drugs before birth, they need close monitoring for health problems.
• There are other safer medications for treating high blood pressure or heart failure during pregnancy.
• Also, women who can become pregnant should generally avoid these drugs.
• If they need treatment, they should choose other safer options.

Perindopril use during breastfeeding:

• Perindopril and its product, perindoprilat, are found in breast milk.
• When measuring the amount a baby might get from breastfeeding, it's really small (less than 2% of a typical dose the mother might take).
• Generally, if this number is under 10%, it's seen as okay for breastfeeding.
• This small amount was found after a mother took a 10 mg dose of perindopril twice a day for 2 weeks.
• Even with this, the company that makes perindopril suggests being careful when giving it to breastfeeding moms.

Dose adjustment in renal disease:

• If your kidneys filter more than 30 mL/minute (meaning they work relatively well): Start with 2 mg of Perindopril each day, and the highest dose you should take is 8 mg daily.
• If your kidneys filter less than 30 mL/minute (meaning they don't work as well): It's generally not advised to use Perindopril. But if someone's kidneys filter between 15 and 30 mL/minute, they might be told to take 2 mg every other day, according to some Canadian guidelines.
• If you're on hemodialysis (a treatment to clean your blood): Perindopril and its by-products can be removed during dialysis. On days you get dialysis, you might be told to take 2 mg after the treatment, as per some Canadian recommendations.

Dose adjustment in liver disease:

• The company that makes Perindopril hasn't given any specific dose changes for people with liver problems.
• But, since liver issues can increase how much of the drug is in the body, you should be careful when using it.

Common Side Effects of Perindopril (Coversyl):

• Central nervous system:
  • Headache
• Respiratory:
  • Cough

Rare Side Effects of Perindopril (Coversyl):

• Cardiovascular:
  • ECG Abnormality
  • Chest Pain
  • Palpitations
  • Edema
• Central Nervous System:
  • Paresthesia
  • Sleep Disorder
  • Drowsiness
  • Depression
  • Nervousness
  • Hypertonia
• Dermatologic:
  • Skin Rash
• Endocrine & Metabolic:
  • Menstrual Disease
  • Increased Serum Triglycerides
• Gastrointestinal:
  • Nausea
  • Abdominal Pain
  • Vomiting
  • Dyspepsia
  • Flatulence
  • Diarrhea
• Genitourinary:
  • Sexual Disorder
  • Proteinuria
  • Urinary Tract Infection
• Hepatic:
  • Increased Serum ALT
• Hypersensitivity:
  • Seasonal Allergy
• Infection:
  • Viral Infection
• Neuromuscular & Skeletal:
  • Arthralgia
  • Back Pain
  • Myalgia
  • Leg Pain
  • Arthritis
  • Arm Pain
  • Neck Pain
  • Weakness
• Otic:
  • Otic Infection
  • Tinnitus
• Respiratory:
  • Rhinitis
  • Sinusitis
  • Pharyngitis
  • Upper Respiratory Tract Infection
• Miscellaneous:
  • Fever

Contraindication:

You shouldn't take Perindopril if:

• You're allergic to it, other similar drugs (ACE inhibitors), or any of its ingredients.
• You've had swelling reactions (like around the lips or eyes) for unknown reasons or due to genetics.
• You're taking a drug called aliskiren and have diabetes.
• You're taking, or have recently taken, a drug called a neprilysin inhibitor (like sacubitril).

Additional rules for Canada (not in the U.S.):

• Don't mix Perindopril with aliskiren if you have serious kidney problems.
• Women who are, or plan to be, pregnant shouldn't take it. Also, women who can get pregnant but aren't using reliable birth control shouldn't use it.
• Don't take it if you're breastfeeding.
• It's not for people with certain rare sugar digestion problems.
• Avoid it if you're on sacubitril/valsartan.
• Don't use if you're getting certain treatments where blood contacts specific surfaces.
• Avoid it if you have narrowing of one or both arteries supplying the kidneys.

Warnings and precautions

Angioedema

• Angioedema is sudden swelling under the skin, which can happen at any time when taking ACE inhibitors like Perindopril.
• This swelling can be dangerous if it happens in the head and neck area, as it can block breathing. It can also happen in the intestine, causing stomach pain.
• Black patients, those with a genetic tendency for angioedema, or those who had angioedema with ACE inhibitors before, are at a higher risk.
• The risk of getting this swelling is also higher if you're taking certain other drugs, like everolimus or sacubitril.
• If there's swelling in areas like the tongue or throat, it's urgent because it can block breathing. Such patients need close and extended monitoring.
• People who've had certain throat surgeries might also have a higher chance of this dangerous swelling.
• If someone had angioedema with an ACE inhibitor before, they shouldn't take this kind of drug again. It's too risky.

Cholestatic jaundice

• A very rare side effect of ACE inhibitors, like Perindopril, is cholestatic jaundice. This is a condition where bile can't flow from the liver to the intestine, leading to yellowing of the skin or eyes (jaundice).
• This problem can get worse, leading to severe liver damage that might be deadly.
• If someone taking this drug has a big increase in liver enzymes (a sign of liver issues) or turns yellow (jaundice), they should stop taking the medicine immediately.

Cough:

• A common side effect of ACE inhibitors, like Perindopril, is a persistent dry cough.
• This kind of cough usually starts within a few months of starting the medicine and isn't accompanied by phlegm.
• If the drug is stopped, the cough should go away within 1 to 4 weeks.
• Before deciding to stop the medicine because of the cough, doctors should check if something else might be causing it, like fluid buildup in the lungs for heart failure patients.

Hematologic effects

• Captopril, a drug similar to Perindopril, can cause low levels of certain blood cells. This includes very low white blood cell counts, which are crucial for fighting infections, and issues with red blood cells and platelets.
• People with kidney problems have a higher chance of getting low white blood cell counts when taking these drugs.
• If someone has both kidney problems and certain diseases that affect the whole body (like lupus), their risk is even higher.
• For these patients, regular blood tests should be done to keep an eye on their blood cell levels.

Hyperkalemia:

• ACE inhibitors, like Perindopril, can cause high potassium levels in the blood, which is called hyperkalemia.
• People with kidney problems, diabetes, or those who are taking certain other medicines or supplements that have potassium are at a higher risk of this happening.
• Be very careful when taking Perindopril with these other potassium-increasing products. If you do, keep a close eye on your potassium levels through regular tests.

Hypersensitivity reactions

• Severe allergic reactions can happen with ACE inhibitors, like Perindopril.
• These reactions are more likely during certain treatments like high-flux hemodialysis or when cleaning bad cholesterol from the blood using specific materials.
• There have also been rare cases where people receiving treatments for bee or wasp stings had allergic reactions while on ACE inhibitors.

Hypotension/syncope

• Taking Perindopril can lead to very low blood pressure, which might make some people faint, especially when first starting the drug.
• People who are dehydrated or have low blood volume are more likely to experience this. It's a good idea to fix dehydration before starting the medicine.
• Be especially careful and watch closely when starting the medicine or increasing the dose.
• Even if someone's blood pressure drops too much, it doesn't always mean they have to stop the medicine. For example, for people with heart failure, a lower blood pressure can be a good sign. But, the decrease in blood pressure should be at a safe rate.

Renal function deterioration:

• Perindopril can sometimes worsen kidney function, which might show as increased levels of certain substances (like BUN and creatinine) in the blood.
• People with certain conditions where the kidneys aren't getting enough blood, like narrowed kidney arteries or heart failure, are more at risk. That's because their kidneys rely on a tight balance of factors, including a substance called angiotensin II.
• In some cases, the kidneys might start working poorly, leading to conditions like reduced urine output, acute kidney failure, or a buildup of waste products in the blood.
• Small rises in creatinine might happen when starting the drug, but think about stopping the drug if the kidney function gets much worse or keeps declining.

Aortic stenosis

• Be careful when giving Perindopril to people with severe aortic stenosis, a condition where the heart's aortic valve is narrowed.
• The drug might decrease the blood flow to the heart muscle, which could lead to reduced oxygen supply to the heart (ischemia).

Ascites:

• Don't use Perindopril in people with ascites, which is a buildup of fluid in the abdomen, especially if it's because of liver disease or if other treatments haven't worked.
• If someone with this fluid buildup from liver disease really needs to take Perindopril, keep a close watch on their blood pressure and how their kidneys are working. This is to prevent the kidneys from failing quickly.

Cardiovascular disease

• When starting Perindopril in people with heart or brain blood flow problems, be very watchful. A drop in blood pressure in these patients might lead to serious issues like a heart attack or stroke.
• If the blood pressure drops too low, giving fluids might help bring it back up, and then you might be able to continue the medicine.
• But if their blood pressure keeps getting too low, it's best to stop the medicine.

Collagen vascular disease:

• Be careful when giving Perindopril to people with diseases that affect the body's connective tissue, especially if they also have kidney problems.
• These patients might have a higher risk of issues with their blood cells.

Hepatic impairment

• Be careful when giving Perindopril to people with liver issues.

Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

• Be cautious when using Perindopril in people with hypertrophic cardiomyopathy, a condition where the heart muscle is thicker than normal, especially if they also have a blockage that affects blood flow out of the heart.
• This is because the drug might reduce the pressure against which the heart pumps, which could make the symptoms of this heart condition worse.

Renal artery stenosis

• Be cautious when using Perindopril in people with narrowed arteries to one or both kidneys and who haven't had a stent (a device to keep the artery open).
• Generally, it's best to avoid the drug in these people because of a high chance of worsening kidney function, unless the benefits really outweigh the risks.

Renal impairment

• Be careful when giving Perindopril to people with kidney problems.
• They might need a different dose. Increase the dose slowly, because going up too fast could make their kidney problems worse.

Perindopril: Drug Interaction

Monitoring parameters:

• General Checks:
  • Blood pressure
  • BUN, serum creatinine, and potassium levels
  • For patients with diseases affecting connective tissue or kidney issues, regularly check complete blood count.

Heart Failure Guidelines:

• Initial Checks:
  • 1 to 2 weeks after starting medication.
  • Especially important for patients with low blood pressure, low sodium levels, diabetes, poor kidney function, or taking potassium supplements.

Hypertension Guidelines (2017):

• High Blood Pressure with Heart Disease Risk:
  • If they already have heart issues or a high 10-year risk: Aim for blood pressure below 130/80 mm Hg.
  • If no heart disease risks: Keeping blood pressure below 130/80 mm Hg might be a good idea.

Diabetes and High Blood Pressure Guidelines (2019):

• Younger Adults (18 to 65 years):
  • Without heart disease and low 10-year heart risk: Aim for blood pressure below 140/90 mm Hg.
  • With heart disease or high 10-year risk: Aiming for blood pressure below 130/80 mm Hg might be good if safe.
• Older Adults (Above 65 years):
  • Healthy or with some health issues: Aim for blood pressure below 140/90 mm Hg.
  • With many health problems: Aim for blood pressure below 150/90 mm Hg.

How to administer?

• When to Take: Take it after dinner in the evening.
• Precautions After Taking:
  • Sit down for 15-30 minutes after taking the medicine.
  • This helps avoid a big drop in blood pressure, especially during the first week.

Mechanism of action of Perindopril (Coversyl):

• Perindopril is a medicine that changes into perindoprilat in the body.
• It works by blocking a process that normally turns a substance called angiotensin I into another one called angiotensin II.
• By doing this, it prevents angiotensin II from making blood vessels narrow and tight.
• This leads to less angiotensin II in the body, which then causes more activity from an enzyme called renin and less release of a hormone called aldosterone.

Starting to Work:

• Maximum effect: 1 to 2 hours after taking.

Binding to Proteins:

• Perindopril: Binds to ~60% of proteins.
• Perindoprilat (its active form): Binds to 10% to 20% of proteins.

Breaking Down in the Body:

• It's mostly broken down in the liver.
• Turns into its active form, perindoprilat (around 17% to 20% of the dose) and other inactive parts.

Getting Into the Blood:

• Perindopril: About 75% gets into the blood.
• Perindoprilat: About 25% gets into the blood (drops to ~16% if taken with food).

How Long It Stays in the Body:

• Original drug: 1.5 to 3 hours.
• Active part (perindoprilat):
  • Working effect: 3 to 10 hours.
  • Total time in the body: 30 to 120 hours.

Reaching Maximum Levels in Blood:

• After regular use:
  • Perindopril: About 1 hour.
  • Perindoprilat: 3 to 7 hours (levels are 2 to 3 times higher after regular use).
• For heart failure patients:
  • Perindoprilat: 6 hours.

Leaving the Body:

• Most leaves through urine (75%), with 4% to 12% unchanged.

International Brands of Perindopril:

• Aceon
• AG-Perindopril
• APO-Perindopril
• Auro-Perindopril
• Coversyl
• JAMP-Perindopril
• M-Perindopril Erbumine
• MAR-Perindopril
• MINT-Perindopril
• PMS-Perindopril
• Priva-Perindopril Erbumine
• RIVAPerindopril
• SANDOZ Perindopril Erbumine
• TEVA-Perindopril
• Acerpril
• Acertil
• Acertil AR
• Acetec
• Adwipril
• Articel
• Bioprexum
• Covapril
• Coverene
• Coverex
• Covergim
• Coversum
• Coversyl
• Covinace
• Covrix
• Dopril
• Dorover
• Hypergo
• Indopril
• Indosyl Mono
• Inopil
• Myden
• Nexazin
• Pendrex
• Percarnil
• Pericard
• Perigard
• Perinace
• Perindal
• Perindo
• Peryndopryl Anpharm
• Prenesa
• Prenessa
• Prestarium
• Prindace
• Prinwin
• Protectopril
• Provinace
• Versil

Perindopril Brands In Pakistan: