Enalapril Accord
ACE Inhibitor for Hypertension and Heart Failure
Enalapril Accord contains enalapril maleate, an ACE inhibitor (angiotensin-converting enzyme inhibitor) used to treat high blood pressure and heart failure. It works by relaxing blood vessels to lower blood pressure and reduce the heart's workload. This medication requires a prescription and is taken orally once or twice daily.
Quick Facts
Key Takeaways
- Enalapril Accord is an ACE inhibitor that lowers blood pressure by preventing the formation of angiotensin II, a substance that narrows blood vessels.
- It is used to treat hypertension (high blood pressure) and heart failure, reducing the risk of hospitalization and potentially extending survival in heart failure patients.
- The medication usually takes effect within 1 hour, with full blood pressure benefits often requiring several weeks of treatment.
- It must not be used during pregnancy, especially during the last 6 months, as it can cause serious harm to the unborn baby.
- Common side effects include dizziness, dry cough, and fatigue. Seek immediate medical attention if you experience swelling of the face, lips, tongue, or throat (angioedema).
What Is Enalapril Accord and What Is It Used For?
Quick Answer: Enalapril Accord is an oral ACE inhibitor medication containing enalapril maleate. It is primarily used to treat high blood pressure (hypertension) and heart failure by relaxing blood vessels and reducing the heart's workload.
Enalapril Accord contains the active substance enalapril maleate, which belongs to a group of medicines known as ACE inhibitors (angiotensin-converting enzyme inhibitors). ACE inhibitors are among the most widely prescribed classes of cardiovascular medications worldwide. They work by blocking the angiotensin-converting enzyme, which plays a central role in the renin-angiotensin-aldosterone system (RAAS) — a hormonal system that regulates blood pressure and fluid balance in the body.
When enalapril is taken orally, it is converted in the liver to its active form, enalaprilat. This active metabolite inhibits ACE, preventing the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor (a substance that narrows blood vessels) and also stimulates the release of aldosterone, a hormone that causes sodium and water retention. By blocking this pathway, enalapril causes blood vessels to dilate (widen), blood pressure to decrease, and the heart's workload to be reduced.
Enalapril Accord is prescribed for the following indications:
- Hypertension (high blood pressure): Enalapril effectively lowers both systolic and diastolic blood pressure. According to the European Society of Cardiology (ESC) and European Society of Hypertension (ESH) guidelines, ACE inhibitors are recommended as first-line agents for hypertension management in many patient populations, including those with diabetes, chronic kidney disease, or heart failure.
- Heart failure (weakened heart function): Enalapril is one of the most extensively studied ACE inhibitors for heart failure. The landmark CONSENSUS and SOLVD trials demonstrated that enalapril significantly reduces mortality and hospitalization rates in patients with symptomatic heart failure. It may reduce symptoms such as shortness of breath, fatigue after light physical activity, and swelling of the ankles and feet.
The medication typically begins working within approximately 1 hour after oral administration, with peak blood pressure-lowering effects occurring at 4 to 6 hours. The duration of action extends for at least 24 hours, allowing for convenient once-daily dosing in most patients. However, some individuals may require several weeks of treatment before optimal blood pressure control is achieved.
Enalapril Accord is manufactured by Accord Healthcare B.V. and is available as a generic formulation, making it an affordable option for long-term cardiovascular treatment. The active ingredient, enalapril maleate, has been used clinically since the 1980s and has an extensive safety and efficacy profile supported by decades of clinical experience and multiple large-scale randomized controlled trials.
What Should You Know Before Taking Enalapril Accord?
Quick Answer: Do not take Enalapril Accord if you are allergic to enalapril or other ACE inhibitors, have a history of angioedema, are pregnant (especially in the last 6 months), or are taking sacubitril/valsartan or aliskiren with diabetes/kidney impairment. Tell your doctor about all medical conditions and medications before starting treatment.
Contraindications
You must not take Enalapril Accord in the following situations:
- You are allergic to enalapril maleate or any other ingredient in the tablets
- You have previously had an allergic reaction to another ACE inhibitor
- You have a history of angioedema (swelling of the face, lips, mouth, tongue, or throat causing difficulty swallowing or breathing) of unknown cause or hereditary angioedema
- You have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren
- You are in the last 6 months of pregnancy (it is also advisable to avoid enalapril during early pregnancy)
- You are taking or have recently taken sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, due to an increased risk of angioedema
Warnings and Precautions
Before starting treatment with Enalapril Accord, it is essential to inform your doctor about your complete medical history. Certain conditions require extra caution or dose adjustments. ACE inhibitors as a class carry specific risks that need to be monitored, particularly during the initial stages of therapy.
Talk to your doctor or pharmacist before taking Enalapril Accord if you have or have had any of the following:
- Heart problems: including coronary artery disease, aortic stenosis, or hypertrophic cardiomyopathy. ACE inhibitors can cause symptomatic hypotension, particularly in patients with volume depletion or severe heart failure.
- Cerebrovascular disease: Any condition affecting the blood vessels in the brain, as excessive blood pressure reduction may increase the risk of stroke in vulnerable patients.
- Blood disorders: Such as neutropenia (low white blood cell count), agranulocytosis, thrombocytopenia (low platelet count), or anemia. ACE inhibitors can rarely affect blood cell production.
- Liver disease: Enalapril is converted to its active form in the liver. Liver impairment may affect drug metabolism and increase the risk of hepatic complications.
- Kidney disease: Including history of kidney transplant. Your doctor may need to adjust the dose and monitor kidney function and potassium levels more closely.
- Diabetes: Blood glucose levels should be monitored carefully, especially during the first month of treatment. ACE inhibitors may enhance the effect of insulin and oral antidiabetic agents, potentially increasing the risk of hypoglycemia.
- History of angioedema: You should be aware that Black patients have an increased risk of angioedema with ACE inhibitors compared to other populations.
- Low blood pressure: You may experience weakness or dizziness, especially when standing up (orthostatic hypotension).
- Connective tissue disease: Such as systemic lupus erythematosus, rheumatoid arthritis, or scleroderma, particularly if you are on immunosuppressive therapy, allopurinol, or procainamide.
- Severe vomiting or diarrhea: Recent episodes may cause dehydration and electrolyte imbalances, increasing the risk of hypotension.
Clinical evidence indicates that ACE inhibitors, including enalapril, may be less effective at lowering blood pressure in Black patients compared to other populations. Your doctor will consider this when choosing the most appropriate treatment for you.
If you are scheduled for any of the following procedures, inform your doctor that you are taking Enalapril Accord:
- Surgery or anaesthesia (including dental procedures)
- LDL apheresis (a treatment to remove cholesterol from the blood)
- Desensitization therapy for bee or wasp sting allergies
Pregnancy and Breastfeeding
Enalapril Accord must not be used during the last 6 months of pregnancy, as it can cause serious harm to the unborn baby, including renal failure, oligohydramnios (reduced amniotic fluid), skull deformities, and neonatal death. The risk is particularly high during the second and third trimesters. Even during early pregnancy, enalapril is not recommended, and your doctor will typically suggest switching to an alternative antihypertensive medication before conception or as soon as pregnancy is confirmed.
Enalapril is excreted in breast milk in small amounts. This medication is not recommended during breastfeeding, especially if the infant is a newborn or was born prematurely. For breastfeeding mothers with older infants, your doctor will discuss the potential benefits and risks of continuing enalapril compared to alternative treatments.
Driving and Using Machines
Enalapril Accord may cause dizziness or drowsiness in some patients, particularly during the initial stages of treatment or after dose adjustments. If you experience these effects, do not drive a vehicle or operate machinery until you know how the medication affects you. Be particularly cautious when rising quickly from a sitting or lying position.
How Does Enalapril Accord Interact with Other Drugs?
Quick Answer: Enalapril Accord interacts with many medications, including ARBs, aliskiren, potassium supplements, lithium, NSAIDs, and diabetes medications. Always inform your doctor about all medicines you take, including herbal products and supplements.
Drug interactions can alter how Enalapril Accord works or increase the risk of serious side effects. It is essential to inform your doctor or pharmacist about all medications you are currently taking, have recently taken, or plan to take. This includes prescription medicines, over-the-counter drugs, herbal remedies, and nutritional supplements.
Major Interactions
The following drug interactions are considered clinically significant and may require dose adjustments, additional monitoring, or avoidance of combination therapy:
| Drug / Drug Class | Interaction Effect | Clinical Significance |
|---|---|---|
| Aliskiren | Dual RAAS blockade; increased risk of hypotension, hyperkalemia, and renal impairment | Contraindicated in patients with diabetes or renal impairment |
| ARBs (e.g., valsartan, telmisartan) | Dual RAAS blockade; excessive blood pressure lowering and kidney damage | Generally not recommended, especially with diabetic nephropathy |
| Sacubitril/Valsartan | Increased risk of angioedema | Contraindicated; allow 36-hour washout period |
| Potassium supplements / K-sparing diuretics | Risk of life-threatening hyperkalemia | Close monitoring of serum potassium required |
| Lithium | Increased lithium levels and toxicity risk | Monitor lithium levels; dose adjustment may be needed |
| NSAIDs (incl. COX-2 inhibitors) | Reduced antihypertensive effect; increased renal impairment risk | Monitor blood pressure and kidney function |
Other Notable Interactions
The following medications may also interact with Enalapril Accord and should be discussed with your healthcare provider:
- Diabetes medications (insulin and oral antidiabetics): Enhanced blood sugar-lowering effect, potentially increasing risk of hypoglycemia. Blood glucose monitoring is particularly important during the first month of combination therapy.
- Diuretics and other antihypertensives: Additive blood pressure-lowering effect. Dose reduction of one or both agents may be necessary. Patients on diuretics are at particular risk of first-dose hypotension.
- Tricyclic antidepressants and antipsychotics: May enhance the blood pressure-lowering effect of enalapril, increasing the risk of orthostatic hypotension.
- Sympathomimetics (found in some cold, cough, and weight-loss medications): May reduce the antihypertensive effect of enalapril.
- Gold therapy (sodium aurothiomalate): Nitritoid reactions (flushing, nausea, vomiting, hypotension) have been reported rarely with concomitant ACE inhibitor use.
- mTOR inhibitors (temsirolimus, sirolimus, everolimus): Increased risk of angioedema when used together with ACE inhibitors.
- Neprilysin inhibitors (e.g., racecadotril, vildagliptin, sacubitril): Increased risk of angioedema. See contraindications regarding sacubitril/valsartan.
- Trimethoprim / Trimethoprim-sulfamethoxazole: Can increase potassium levels when combined with ACE inhibitors.
- Heparin: May increase potassium levels in combination with ACE inhibitors.
- Aspirin and thrombolytics: May be used together under medical supervision, but discuss with your doctor.
- Alcohol: Can enhance the blood pressure-lowering effect, increasing the risk of dizziness or fainting.
Enalapril Accord can be taken with or without food. Most patients take it with a glass of water. Avoid excessive intake of potassium-rich foods (bananas, oranges, potassium-containing salt substitutes) without medical advice, as enalapril can increase potassium levels.
What Is the Correct Dosage of Enalapril Accord?
Quick Answer: For hypertension, the usual starting dose is 5–20 mg once daily, with a maximum of 40 mg daily. For heart failure, start at 2.5 mg once daily, gradually increasing to a maximum of 40 mg daily in divided doses. Always follow your doctor's specific dosing instructions.
Always take Enalapril Accord exactly as your doctor or pharmacist has told you. Do not take more tablets than prescribed. It is important to continue taking this medication as directed, even if you feel well, as high blood pressure often has no noticeable symptoms. The score line on the tablets is intended only to help you break the tablet if you have difficulty swallowing it whole, not to divide the dose.
Adults
| Indication | Starting Dose | Maintenance Dose | Maximum Dose |
|---|---|---|---|
| Hypertension | 5–20 mg once daily | 20 mg once daily | 40 mg once daily |
| Heart failure | 2.5 mg once daily | 20 mg daily (1 or 2 doses) | 40 mg daily (in 2 doses) |
| Moderate renal impairment | 5–10 mg daily | Adjust based on response | As tolerated |
| Severe renal impairment | 2.5 mg daily | Adjust based on response | As tolerated |
| Dialysis patients | 2.5 mg on dialysis days | Adjust based on blood pressure | As tolerated |
For hypertension, some patients may require a lower starting dose, particularly those who are taking diuretics, have renal impairment, or are volume-depleted. Your doctor will gradually increase the dose based on your blood pressure response, typically at intervals of 1 to 2 weeks. The dose will be titrated slowly, starting at the lowest effective dose and increasing only if necessary to reach target blood pressure levels.
For heart failure, treatment initiation requires careful dose titration under medical supervision. The starting dose is intentionally low (2.5 mg) to minimize the risk of first-dose hypotension. The dose is then gradually increased over weeks to the maximum tolerated dose, which has been shown in clinical trials to provide the greatest benefit in reducing mortality and hospitalization.
Children
Experience with Enalapril Accord in children with high blood pressure is limited. The medication should only be used in children who can swallow tablets. The dose is calculated based on the child's weight and blood pressure:
Pediatric Dosing
- Children weighing 20–50 kg: Starting dose of 2.5 mg daily; maximum dose of 20 mg daily
- Children weighing over 50 kg: Starting dose of 5 mg daily; maximum dose of 40 mg daily
This medication is not recommended for neonates (newborns in the first weeks of life) or children with kidney problems.
Elderly Patients
Elderly patients often have reduced kidney function, which affects the clearance of enalapril from the body. The dose should be determined by your doctor based on your kidney function. More frequent monitoring of blood pressure, kidney function, and potassium levels may be needed in elderly patients.
Missed Dose
If you forget to take a dose, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. If you frequently miss doses, consider setting a daily reminder or using a pill organizer to help maintain consistent medication adherence.
Overdose
If you have taken more Enalapril Accord than prescribed, seek immediate medical attention or contact a poison control center. Take the medication packaging with you. The most likely symptoms of overdose include feeling faint or dizzy due to a sudden or excessive drop in blood pressure. Overdose management is primarily supportive, focusing on blood pressure monitoring and intravenous fluids.
What Are the Side Effects of Enalapril Accord?
Quick Answer: Very common side effects (more than 1 in 10 people) include dizziness, weakness, blurred vision, and cough. If you experience swelling of the face, lips, tongue, or throat, stop taking the medication and seek immediate medical attention.
Like all medicines, Enalapril Accord can cause side effects, although not everybody gets them. Most side effects are mild and transient, particularly those occurring at the start of treatment. However, some side effects can be serious and require immediate medical attention.
- Swelling of the face, lips, tongue, or throat that may cause difficulty breathing or swallowing (angioedema)
- Swelling of hands, feet, or ankles
- Raised red skin rash (hives/urticaria)
Be aware that Black patients have an increased risk of angioedema with ACE inhibitors.
When you first start taking this medication, you may feel dizzy or faint. This is caused by a drop in blood pressure and usually improves as your body adjusts to the medication. Lying down may help relieve these symptoms.
Very Common
May affect more than 1 in 10 people
- Dizziness
- Weakness or feeling unwell
- Blurred vision
- Cough (dry, persistent)
Common
May affect up to 1 in 10 people
- Headache, depression, fainting (syncope), taste disturbances
- Low blood pressure, changes in heart rhythm, palpitations, chest pain (angina)
- Shortness of breath
- Diarrhea, abdominal pain
- Fatigue, skin rash
- Allergic reactions with swelling (angioedema)
- Elevated potassium levels, increased blood creatinine
Uncommon
May affect up to 1 in 100 people
- Flushing, rapid or irregular heartbeat
- Sudden blood pressure drop
- Heart attack or stroke (in high-risk patients with very low blood pressure)
- Confusion, insomnia or drowsiness, nervousness
- Tingling or numbness, vertigo, tinnitus (ringing in ears)
- Runny nose, sore throat, hoarseness, asthma-related chest tightness
- Nausea, vomiting, constipation, indigestion, dry mouth, stomach ulcer
- Pancreatitis, intestinal obstruction (ileus)
- Impaired kidney function, kidney failure
- Muscle cramps, itching, hives, hair loss
- Increased sweating, fever, impotence
- Low blood sugar or sodium, elevated blood urea
Rare
May affect up to 1 in 1,000 people
- Raynaud's phenomenon (very cold, white hands and feet due to low blood flow)
- Blood disorders: low white blood cells, low red blood cells, low hemoglobin, low platelets
- Bone marrow depression
- Swollen lymph nodes
- Autoimmune diseases
- Lung inflammation (pneumonitis), fluid accumulation in the lungs
- Inflammation of the nose, mouth, gums, tongue, lips, or throat
- Liver problems: hepatitis, jaundice, elevated liver enzymes
- Severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, pemphigus
- Breast enlargement in men (gynecomastia)
Very Rare
May affect up to 1 in 10,000 people
- Intestinal angioedema (swelling of the intestinal wall)
If you experience any side effects, including those not listed here, talk to your doctor or pharmacist. You can also report side effects directly to your national medicines regulatory authority. By reporting side effects, you help provide more information on the safety of this medicine.
How Should You Store Enalapril Accord?
Quick Answer: Store Enalapril Accord out of the sight and reach of children. No special storage conditions are required. Do not use after the expiry date shown on the packaging.
Proper storage of medications is essential to maintain their effectiveness and safety. Follow these guidelines for storing Enalapril Accord:
- Keep this medicine out of the sight and reach of children at all times.
- Do not use this medicine after the expiry date stated on the blister pack and carton after "EXP." The expiry date refers to the last day of that month.
- No special storage conditions are required for this product. Store at room temperature in a dry place.
- Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.
If you notice any changes in the appearance of the tablets (such as discoloration, crumbling, or unusual odor), do not take them and consult your pharmacist for a replacement. Always keep the tablets in their original blister packaging until you are ready to take them.
What Does Enalapril Accord Contain?
Quick Answer: The active substance is enalapril maleate, available in 2.5 mg, 5 mg, 10 mg, and 20 mg tablets. Inactive ingredients include lactose monohydrate, microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, sodium hydrogen carbonate, and magnesium stearate.
Active Ingredient
The active substance is enalapril maleate, available in four strengths: 2.5 mg, 5 mg, 10 mg, or 20 mg per tablet.
Inactive Ingredients (Excipients)
The other ingredients are:
- Microcelac 100 (containing lactose monohydrate and microcrystalline cellulose)
- Pregelatinized starch
- Croscarmellose sodium
- Sodium hydrogen carbonate
- Magnesium stearate
- Red iron oxide (E172) — in 10 mg and 20 mg tablets only
Lactose: This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Sodium: This medicine contains less than 1 mmol (23 mg) sodium per tablet, meaning it is essentially sodium-free.
Tablet Appearance
| Strength | Appearance | Imprint | Pack Sizes |
|---|---|---|---|
| 2.5 mg | White to off-white, round (5.00 mm), biconvex, uncoated | "ISI" on one side, plain on the other | 28, 30, 50, 100 tablets |
| 5 mg | White to off-white, triangular (6.50 mm), biconvex, uncoated | "IS2" on one side, scored on the other | 20, 28, 30, 56, 60, 90, 100 tablets |
| 10 mg | Light pink to pink, triangular (6.50 mm), biconvex, mottled, uncoated | "IS3" on one side, scored on the other | 20, 28, 30, 56, 60, 90, 100 tablets |
| 20 mg | Light pink to pink, triangular (8.80 mm), biconvex, mottled, uncoated | "IS5" on one side, scored on the other | 14, 20, 28, 30, 60, 90, 100 tablets |
The score line on the 5 mg, 10 mg, and 20 mg tablets is not intended for dividing the tablet into equal doses. It is only to facilitate swallowing. All tablets are supplied in aluminum-aluminum blister packs. Not all pack sizes may be marketed in your country.
Frequently Asked Questions About Enalapril Accord
Enalapril Accord is an ACE inhibitor used to treat high blood pressure (hypertension) and heart failure. It works by relaxing blood vessels, which lowers blood pressure and reduces the workload on the heart. For heart failure patients, it can reduce symptoms such as breathlessness, fatigue, and ankle swelling, and may reduce the need for hospitalization. Some patients with heart failure may also experience improved survival with long-term treatment.
Enalapril Accord typically begins to lower blood pressure within 1 hour of taking the first dose, with the peak effect occurring at 4 to 6 hours. The blood pressure-lowering effect lasts for at least 24 hours. However, it may take several weeks of consistent daily use to achieve the full therapeutic benefit and optimal blood pressure control. For heart failure, improvements in symptoms and exercise tolerance may take weeks to months.
No. Enalapril Accord must not be used during the last 6 months of pregnancy, as it can cause serious harm to the developing baby, including kidney problems, reduced amniotic fluid, and skull deformities. It is also not recommended during early pregnancy. If you are planning to become pregnant or discover you are pregnant while taking Enalapril Accord, contact your doctor immediately. Your doctor will advise you to stop the medication and prescribe a safe alternative antihypertensive.
The most common side effects (affecting more than 1 in 10 people) include dizziness, weakness or feeling unwell, blurred vision, and a dry persistent cough. The cough is a well-known class effect of ACE inhibitors and occurs because enalapril increases levels of bradykinin in the lungs. If the cough is bothersome, speak to your doctor, who may suggest switching to an alternative medication such as an angiotensin receptor blocker (ARB). Other common side effects include headache, fatigue, low blood pressure, diarrhea, and skin rash.
Alcohol can enhance the blood pressure-lowering effect of Enalapril Accord, which may cause dizziness, lightheadedness, or fainting. While moderate alcohol consumption may be acceptable for some patients, it is best to discuss safe limits with your doctor. Be especially cautious during the first few days of treatment or after a dose increase, as these are times when blood pressure-lowering effects may be more pronounced.
If you miss a dose of Enalapril Accord, simply skip the missed dose and take your next dose at the usual time. Do not take a double dose to compensate for the forgotten one. Consistent daily dosing is important for optimal blood pressure control. If you regularly forget doses, ask your pharmacist about pill organizers, alarms, or smartphone apps that can help you remember.
References and Sources
This article is based on the official product information (Summary of Product Characteristics), international medical guidelines, and peer-reviewed research. All medical claims are supported by evidence level 1A where applicable.
- European Medicines Agency (EMA). Enalapril Accord – Summary of Product Characteristics. Available at: www.ema.europa.eu
- Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021-3104. doi:10.1093/eurheartj/ehy339
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021;42(36):3599-3726. doi:10.1093/eurheartj/ehab368
- The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med. 1987;316:1429-1435. doi:10.1056/NEJM198706043162301
- The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293-302. doi:10.1056/NEJM199108013250501
- World Health Organization (WHO). Model List of Essential Medicines – 23rd list, 2023. Available at: www.who.int
- British National Formulary (BNF). Enalapril maleate. National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248. doi:10.1016/j.jacc.2017.11.006
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians and clinical pharmacologists with expertise in cardiovascular medicine and pharmacotherapy.
iMedic Medical Editorial Team — specialists in cardiology, internal medicine, and clinical pharmacology with documented academic background and clinical experience.
iMedic Medical Review Board — independent panel of medical experts who review all content according to ESC, AHA, and WHO guidelines using the GRADE evidence framework.
Evidence standard: All medical claims in this article are based on peer-reviewed research, official product information (SmPC/PIL), and international clinical guidelines. The evidence level is 1A where applicable, based on systematic reviews and meta-analyses of randomized controlled trials.
Conflict of interest: None. iMedic receives no commercial funding and has no financial relationships with pharmaceutical companies.