Amlodipine and Benazepril

Amlodipine and benazepril is a combination medicine used to treat high blood pressure. Different products in this family have slightly different approved uses:

• Amlodipine and benazepril hydrochloride capsules (including Lotrel and generics) are approved to treat high blood pressure (hypertension) in adults — typically used when one blood pressure medicine alone hasn't worked well enough, or when amlodipine by itself causes swelling.
• Amlodipine besylate tablets (a separate product) are approved for high blood pressure, chronic stable angina (chest pain with predictable exertion), vasospastic angina (Prinzmetal's or variant angina, a type of spasm-related chest pain), and reducing cardiovascular risk in patients with angiographically documented coronary artery disease (CAD) without heart failure.
• Lowering blood pressure reduces the risk of strokes, heart attacks, and cardiovascular death.

This combination pairs two medicines that lower blood pressure in different ways. Benazepril is an ACE inhibitor — it blocks an enzyme (angiotensin-converting enzyme) that produces a substance called angiotensin II, which normally constricts blood vessels. Less angiotensin II means more relaxed blood vessels and lower blood pressure. Amlodipine is a calcium channel blocker — it prevents calcium from entering the smooth muscle cells in blood vessel walls. Without that calcium signal, vessel walls relax, reducing the resistance the heart has to pump against.

Because the two drugs work through separate pathways, combining them produces a stronger blood pressure reduction. As a bonus, benazepril partially counters the ankle swelling that amlodipine can sometimes cause on its own.

The combination capsule is taken once daily by mouth, with or without food. The full blood pressure-lowering effect is largely reached within about two weeks. Your prescriber will start at a low dose and adjust based on your response — do not change the dose on your own.

• Combination capsules (Lotrel and generics) are not recommended if your kidney function is severely reduced.
• If you have liver disease or are older, your doctor may start you at a lower dose because amlodipine stays in your body longer.
• Amlodipine besylate tablets (a different product) follow their own dosing schedule set by your prescriber.

Most side effects are mild and often improve over time. The most commonly reported ones include:

• Dry, persistent cough — very characteristic of ACE inhibitors like benazepril
• Swelling (edema), particularly in the ankles or feet — less common with the combination than with amlodipine alone
• Headache
• Dizziness
• Flushing or hot flashes
• Nausea, dry mouth, or stomach upset
• Fatigue or weakness

Get emergency help right away if you develop sudden swelling of your face, lips, tongue, or throat (angioedema), severe dizziness or fainting, worsening chest pain, or yellowing of the skin or eyes — these can be signs of a serious reaction.

• Fetal harm (Boxed Warning): This medicine can cause serious injury or death to an unborn baby, especially in the second and third trimesters. Stop it immediately if you become pregnant and call your doctor.
• Angioedema: Rare but potentially fatal swelling of the throat or airway can occur. Black patients are at higher risk. Stop the medicine and seek emergency care if swelling of the face, tongue, or throat develops. Abdominal angioedema (gut swelling with pain) can also occur.
• Low blood pressure: Most likely if you are dehydrated, on a low-salt diet, on diuretics, or have heart failure. Sit or stand up slowly if you feel lightheaded.
• Kidney function: This medicine can affect how well the kidneys work. Your doctor may monitor kidney function periodically, especially if you have existing kidney disease or take NSAIDs.
• High potassium (hyperkalemia): Benazepril can raise potassium levels, which can affect heart rhythm. Avoid potassium supplements or salt substitutes containing potassium unless your doctor approves.
• Liver problems: Rare cases of serious liver injury have been reported with ACE inhibitors. Contact your doctor if you develop jaundice or unusual fatigue.
• Worsening angina or heart attack: Starting or raising the amlodipine dose can rarely trigger worsening chest pain or a heart attack in people with severe coronary artery disease.

Several medicines and supplements can interact with amlodipine and benazepril — always tell your prescriber and pharmacist everything you take:

• Potassium supplements or potassium-sparing diuretics (e.g., spironolactone, amiloride) — can raise potassium to dangerous levels when combined with benazepril
• Lithium — benazepril raises lithium blood levels, increasing the risk of lithium toxicity
• NSAIDs (ibuprofen, naproxen, COX-2 inhibitors) — reduce blood pressure control and can harm kidney function, especially in older or dehydrated patients
• Simvastatin — amlodipine raises simvastatin exposure; simvastatin doses must be capped when taken with amlodipine
• CYP3A4 inhibitors (certain antifungals, macrolide antibiotics, HIV medicines) — increase amlodipine levels in the blood, raising risk of low blood pressure and swelling
• CYP3A4 inducers (rifampicin, St. John's Wort) — may reduce amlodipine's effectiveness
• Other RAS-blocking medicines (ARBs, aliskiren) — combining them increases risks of low blood pressure, high potassium, and kidney failure; aliskiren must not be combined with this medicine in patients with diabetes
• Injectable gold — can cause flushing, nausea, vomiting, and low blood pressure when used with ACE inhibitors
• Insulin or oral diabetes medicines — benazepril may enhance blood-sugar-lowering effects, raising the risk of low blood sugar
• Neprilysin inhibitors (sacubitril/valsartan) — must not be taken together; wait at least 36 hours after stopping one before starting the other
• mTOR inhibitors (sirolimus, everolimus, temsirolimus) — increase the risk of angioedema when combined with ACE inhibitors

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Pregnancy: Do not take this medicine if you are pregnant or planning to become pregnant. It can cause serious fetal injury or death, especially after the first trimester. Discuss alternative blood pressure treatments with your doctor.
• History of angioedema: Do not take this medicine if you have ever had angioedema (severe swelling), whether or not it was caused by an ACE inhibitor before.
• Allergy: Do not take it if you are allergic to benazepril, amlodipine, or any other ACE inhibitor.
• Neprilysin inhibitor use: Do not start this medicine within 36 hours of stopping sacubitril/valsartan (Entresto), and vice versa.
• Diabetes + aliskiren: Do not combine this medicine with aliskiren if you have diabetes.
• Kidney disease: This combination capsule is not recommended in severe kidney impairment. Mild-to-moderate impairment usually doesn't require a dose change.
• Liver disease: Your doctor may use a lower starting dose since amlodipine builds up more in people with liver problems.
• Older adults: Amlodipine is cleared more slowly with age; lower starting doses may be appropriate.
• Children: Safety and effectiveness of the combination capsule have not been established in pediatric patients.
• Breastfeeding: Small amounts of benazepril and amlodipine pass into breast milk; discuss the risks and benefits with your doctor.

Taking too much of this medicine is most likely to cause a dangerous drop in blood pressure (hypotension) and rapid heart rate. If you suspect an overdose, call 911 or your regional Poison Control Center immediately. Treatment in a hospital setting may include close cardiac monitoring, IV fluids, and other supportive care as needed.

Benazepril blocks ACE activity by 80–90% for at least 24 hours after a dose, leading to sustained lowering of both sitting and standing blood pressure without causing a compensatory increase in heart rate. Amlodipine widens peripheral blood vessels, lowering the resistance the heart pumps against; its blood-pressure-lowering effect lasts at least 24 hours with once-daily dosing and is greater in people with higher baseline blood pressure. In patients with normal kidney function, amlodipine also increases blood flow through the kidneys without reducing the filtration rate.

After taking the combination capsule, amlodipine reaches its peak blood level in 6–12 hours, while benazepril peaks in about 0.5–2 hours and is quickly converted in the liver to its active form (benazeprilat), which peaks at 1.5–4 hours. Both drugs are heavily processed by the liver; amlodipine has a very long effective half-life of about 2 days, and benazeprilat's effective half-life is 10–11 hours, so steady blood levels of both components are reached after about one week of daily dosing. Benazeprilat is cleared mainly by the kidneys, so its levels rise in people with severe kidney impairment; amlodipine is cleared more slowly in older adults and people with liver disease.

Store at 20°-25°C (68°-77°F); Protect from moisture. Dispense in tight container (USP).