Amlodipine and benazepril

Yes

Capsules (mg amlodipine/mg benazepril): 2.5/10; 5/10;5/20; 5/40; 10/20; and 10/40

Lotrel should be stored at room temperature, 15 C - 30 C (59 C - 86 F).

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Take amlodipine and benazepril exactly as prescribed.

Amlodipine and benazepril comes in capsule form and is taken once a day, at the same time each day, with or without food.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of amlodipine and benazepril at the same time.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

The recommended inital dose of amlodipine and benazepril is 1 capsule of amlodipine 2.5mg/benazepril 10mg orally once daily. The antihypertensive effect of amlodipine and benazepril is largely attained within 2 weeks. If blood pressure remains uncontrolled, the dose may be titrated up to amlodipine 10mg/benazepril 40mg once daily. The dosing should be individualized and adjusted according to the patient's clinical response.

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You may take amlodipine and benazepril with or without food. Take the medicine at the same time each day.

Vomiting, diarrhea, or heavy sweating can cause you to become dehydrated. Drink plenty of water each day while you are taking this medicine.

Your blood pressure will need to be checked often, and you may also need frequent blood tests.

If you need surgery, tell the surgeon ahead of time that you are using amlodipine and benazepril. You may need to stop using the medicine for a short time.

You may have very low blood pressure while taking this medicine. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. Prolonged illness can lead to a serious electrolyte imbalance, making it dangerous for you to use amlodipine and benazepril.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Store at room temperature away from moisture and heat.

Get emergency medical help if you have signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat. You may be more likely to have an allergic reaction if you are African-American.

Some side effects may not occur until after you have used the medicine for several months.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• swelling in your hands or feet, rapid weight gain;

• new or worsened chest pain;

• fever, chills, sore throat, body aches, flu symptoms;

• high potassium--nausea, slow or unusual heart rate, weakness, loss of movement; or

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• cough;

• dizziness; or

• swelling in your hands or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Hypertension:

Initial dose: Amlodipine 2.5 mg-Benazepril 10 mg orally once a day
Maintenance dose: Amlodipine 2.5 to 10 mg-Benazepril 10 to 40 mg orally once a day
Maximum dose: Amlodipine: 10 mg/day; Benazepril 80 mg/day

Comments:
-May increase dose after 2 weeks as needed to achieve blood pressure goal.
-Adding benazepril to amlodipine should not be expected to provide additional blood pressure reduction in African Americans.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For amlodipine and benazepril, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to amlodipine and benazepril or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of amlodipine and benazepril combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of amlodipine and benazepril combination in the elderly. However, elderly patients are more likely to have age-related kidney or liver problems, which may require caution and an adjustment in the dose for patients receiving amlodipine and benazepril combination.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking amlodipine and benazepril, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amlodipine and benazepril with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Aliskiren
• Sacubitril

Using amlodipine and benazepril with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alteplase, Recombinant
• Amiloride
• Amiodarone
• Atazanavir
• Azathioprine
• Azilsartan
• Azilsartan Medoxomil
• Candesartan Cilexetil
• Canrenoate
• Ceritinib
• Clarithromycin
• Clopidogrel
• Conivaptan
• Cyclosporine
• Dantrolene
• Digoxin
• Domperidone
• Droperidol
• Eliglustat
• Eplerenone
• Eprosartan
• Everolimus
• Idelalisib
• Irbesartan
• Lacosamide
• Lithium
• Losartan
• Mercaptopurine
• Netupitant
• Olmesartan Medoxomil
• Piperaquine
• Potassium
• Simvastatin
• Sirolimus
• Spironolactone
• Tacrolimus
• Tegafur
• Telaprevir
• Telmisartan
• Triamterene
• Trimethoprim
• Valsartan

Using amlodipine and benazepril with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Amtolmetin Guacil
• Azosemide
• Bromfenac
• Bufexamac
• Bumetanide
• Bupivacaine
• Bupivacaine Liposome
• Capsaicin
• Celecoxib
• Choline Salicylate
• Clonixin
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Dipyrone
• Droxicam
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Furosemide
• Gold Sodium Thiomalate
• Ibuprofen
• Indinavir
• Indomethacin
• Ketoprofen
• Ketorolac
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Nesiritide
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piretanide
• Piroxicam
• Proglumetacin
• Propionic Acid
• Propyphenazone
• Proquazone
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Valdecoxib

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of amlodipine and benazepril. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina (severe chest pain), history of or
• Electrolyte imbalance (e.g., low sodium in the blood) or
• Fluid imbalances (caused by dehydration, vomiting, or diarrhea) or
• Kidney disease or
• Liver disease—Use with caution. May make these conditions worse.

• Angioedema (swelling of the face, lips, tongue, throat, arms, or legs) with other ACE inhibitors, history of—May increase risk of this condition occurring again.

• Aortic stenosis (heart valve problem), severe or
• Heart disease, severe, history of or
• Heart failure, severe, history of—Use with caution. May cause side effects to become worse.

• Congestive heart failure, severe—Use may lead to kidney problems.

• Diabetes or
• Kidney problems—Increased risk of potassium levels in the body becoming too high.

• Diabetic patients who are also taking aliskiren (Tekturna®)—Should not be used in these patients.

• If you have an allergy to amlodipine, benazepril, or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have ever had a very bad or life-threatening reaction called angioedema. Signs may be swelling of the hands, face, lips, eyes, tongue, or throat; trouble breathing; trouble swallowing; unusual hoarseness.
• If you have kidney disease.
• If you are taking a drug that has aliskiren in it and you also have high blood sugar (diabetes) or kidney problems. Check with your doctor or pharmacist if you are not sure if a drug you take has aliskiren in it.
• If you have taken a drug that has sacubitril in it in the last 36 hours.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with amlodipine and benazepril.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Drug/Drug Interactions

Amlodipine

Simvastatin: Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

CYP3A4 Inhibitors:  Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A4 inhibitors to determine the need for dose adjustment.

CYP3A4 Inducers:  No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers.

Benazepril

Potassium Supplements and Potassium-Sparing Diuretics: Benazepril can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. If concomitant use of such agents is indicated, the patient’s serum potassium should be monitored frequently.

Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. When coadministering Amlodipine and Benazepril hydrochloride and lithium, frequent monitoring of serum lithium levels is recommended.

Gold:  Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors):  In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy.

The antihypertensive effect of ACE inhibitors, including benazepril, may be attenuated by NSAIDs.

Antidiabetic Agents:  In rare cases, diabetic patients receiving an ACE inhibitor (including benazepril) concomitantly with insulin or oral antidiabetics may develop hypoglycemia. Such patients should therefore be advised about the possibility of hypoglycemic reactions, and should be monitored accordingly.

Mammalian Target of Rapamycin (mTOR) Inhibitors: The risk of angioedema may be increased in patients receiving coadministration of ACE inhibitors and mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus).

Dual Blockade of the Renin-Angiotensin System (RAS):  Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Amlodipine and Benazepril hydrochloride and other agents that block the RAS.

Do not coadminister aliskiren with Amlodipine and Benazepril hydrochloride in patients with diabetes. Avoid use of aliskiren with Amlodipine and Benazepril hydrochloride

in patients with renal impairment [glomerular filtration rate (GFR) < 60 mL/min].

Neprilysin Inhibitor

Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema. [see Warnings and Precautions 5.1]

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity and mutagenicity studies have not been conducted with this combination.  However, these studies have been conducted with Amlodipine and Benazepril alone (see below). No adverse effects on fertility occurred when the benazepril:amlodipine combination was given orally to rats of either sex at doses up to 15:7.5 mg (benazepril:amlodipine)/kg/day, prior to mating and throughout gestation.

Benazepril:  No evidence of carcinogenicity was found when benazepril was administered to rats and mice for up to 2 years at doses of up to 150 mg/kg/day. When compared on the basis of body surface area, this dose is 18 and 9 times (rats and mice, respectively) the maximum recommended human dose (MRHD) (calculations assume a patient weight of 60 kg). No mutagenic activity was detected in the Ames test in bacteria, in an in vitro test for forward mutations in cultured mammalian cells, or in a nucleus anomaly test. At doses of 50 to 500 mg/kg/day (6 to 60 times the MRHD on a body surface area basis), benazepril had no adverse effect on the reproductive performance of male and female rats.

Amlodipine:  Rats and mice treated with amlodipine maleate in the diet for up to 2 years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg amlodipine/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on a body surface area basis, similar to the MRHD of 10 mg amlodipine/day. For the rat, the highest dose was, on a body surface area basis, about two and a half times the MRHD. (Calculations based on a 60 kg patient.) Mutagenicity studies conducted with amlodipine maleate revealed no drug-related effects at either the gene or chromosome level. There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and females for 14 days prior to mating) at doses of up to 10 mg amlodipine/kg/day (about 10 times the MRHD of 10 mg/day on a body surface area basis).

Reproductive Toxicity

When rats received benazepril:amlodipine at doses ranging from 5:2.5 to 50:25 mg/kg/day, dystocia was observed at an increasing dose-related incidence at all doses tested. On a body surface area basis, the 2.5 mg/kg/day dose of amlodipine is 3.6 times the amlodipine dose delivered when the maximum recommended dose of Amlodipine and Benazepril hydrochloride is given to a 50 kg woman. Similarly, the 5 mg/kg/day dose of benazepril is approximately twice the benazepril dose delivered when the maximum recommended dose of Amlodipine and Benazepril hydrochloride is given to a 50 kg woman. No teratogenic effects were seen when benazepril and amlodipine were administered in combination to pregnant rats or rabbits. Rats received doses of up to 50:25 mg (benazepril:amlodipine)/kg/day (24 times the MRHD on a body surface area basis, assuming a 50 kg woman). Rabbits received doses of up to 1.5:0.75 mg/kg/day (equivalent to the maximum recommended dose of Amlodipine and Benazepril hydrochloride given to a 50 kg woman).

Benazepril:  No teratogenic effects of benazepril were seen in studies of pregnant rats, mice, and rabbits. On a body surface area basis, the maximum doses used in these studies were 60 times (in rats), 9 times (in mice), and about equivalent to (in rabbits) the MRHD (assuming a 50 kg woman).

Amlodipine:  No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses of up to 10 mg amlodipine/kg/day (respectively, about 10 and 20 times the MRHD of 10 mg amlodipine on a body surface area basis) during their respective periods of major organogenesis. (Calculations based on a patient weight of 60 kg.) However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) for rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Lotrel:

2.5/10: Amlodipine 2.5 mg and benazepril hydrochloride 10 mg

5/10: Amlodipine 5 mg and benazepril hydrochloride 10 mg

5/20: Amlodipine 5 mg and benazepril hydrochloride 20 mg

5/40: Amlodipine 5 mg and benazepril hydrochloride 40 mg

10/20: Amlodipine 10 mg and benazepril hydrochloride 20 mg

10/40: Amlodipine 10 mg and benazepril hydrochloride 40 mg

Generic:

2.5/10: Amlodipine 2.5 mg and benazepril hydrochloride 10 mg

5/10: Amlodipine 5 mg and benazepril hydrochloride 10 mg

5/20: Amlodipine 5 mg and benazepril hydrochloride 20 mg

5/40: Amlodipine 5 mg and benazepril hydrochloride 40 mg

10/20: Amlodipine 10 mg and benazepril hydrochloride 20 mg

10/40: Amlodipine 10 mg and benazepril hydrochloride 40 mg

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

See individual agents.

BUN, electrolytes, serum creatinine, and blood pressure. In patients with renal impairment and/or collagen vascular disease, monitor CBC with differential periodically.