Amlodipine and benazepril

Name: Amlodipine and benazepril

What is the dosage for amlodipine and benazepril?

The dose of Lotrel is tailored to the patient's needs. The dose is one capsule once daily.

Amlodipine and Benazepril and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.  

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Amlodipine and benazepril falls into category D. It has been shown that use of amlodipine and benazepril in pregnant women caused some babies to be born with problems. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby. See FDA Warning section for more information.

Amlodipine and Benazepril and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

Minimal amounts of benazepril are excreted into the breast milk. It is unknown whether amlodipine is excreted in human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risks of using amlodipine and benazepril.

What other drugs will affect amlodipine and benazepril?

Many drugs can interact with amlodipine and benazepril. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

  • lithium;

  • probenecid;

  • simvastatin (Zocor, Vytorin);

  • a diuretic or "water pill";

  • gold injections to treat arthritis;

  • a shot for bee-sting allergy;

  • heart or blood pressure medication;

  • insulin or oral diabetes medicine;

  • a potassium supplement (such as K-Dur, Klor-Con), or a salt substitute that contains potassium;

  • an antibiotic--clarithromycin, telithromycin;

  • antifungal medicine--itraconazole, ketoconazole;

  • antiviral medicine to treat HIV/AIDS--indinavir, ritonavir, and others;

  • medicine to prevent organ transplant rejection--cyclosporine, everolimus, sirolimus, tacrolimus, temsirolimus; or

  • a nonsteroidal anti-inflammatory drug (NSAID)--ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete and many other drugs can interact with amlodipine and benazepril. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

amlodipine and benazepril Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common
  • Confusion
  • dizziness, lightheadedness, or fainting
  • fast or irregular heartbeat
  • nervousness
  • numbness or tingling in the hands, feet, or lips
  • shortness of breath
  • swelling of the ankles, feet, or lower legs
  • weakness or heaviness of the legs
Rare
  • Bleeding gums
  • chills
  • fever
  • nausea or vomiting
  • nosebleeds
  • pale skin
  • sores, ulcers, or white spots on the lips, tongue, or inside the mouth
  • stomach pain or bloating with fever, nausea, or vomiting
  • swelling of the face, mouth, hands, or feet
  • trouble with swallowing or breathing (sudden) or hoarseness
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin
Incidence not known
  • Chest pain
  • heartburn
  • pain or burning in the throat

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common
  • Cough (dry and continues)
  • feeling of warmth
  • redness of the face, neck, arms, and occasionally upper chest
  • sleepiness
Incidence not known
  • Acid or sour stomach
  • belching
  • blistering, crusting, irritation, itching, or reddening of the skin
  • body aches or pain
  • cracked, dry, or scaly skin
  • decreased interest in sexual intercourse
  • difficulty having a bowel movement (stool)
  • frequent urination
  • inability to have or keep an erection
  • increased volume of pale, dilute urine
  • indigestion
  • lack or loss of strength
  • loss in sexual ability, desire, drive, or performance
  • muscle or bone pain
  • shakiness in the legs, arms, hands, or feet
  • stomach discomfort or upset
  • sudden sweating
  • swelling
  • tender, swollen glands in the neck
  • trembling or shaking of the hands or feet
  • trouble with sleeping
  • voice changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How is this medicine (Amlodipine and Benazepril) best taken?

Use amlodipine and benazepril as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • Take this medicine at the same time of day.
  • To gain the most benefit, do not miss doses.
  • Keep taking amlodipine and benazepril as you have been told by your doctor or other health care provider, even if you feel well.
  • Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it has been 12 hours or more since the missed dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Dosage Forms and Strengths


Amlodipine and Benazepril hydrochloride capsules USP are available as follows:

2.5 mg/10 mg, 5 mg/10 mg, 5 mg/20 mg, 5 mg/40 mg, 10 mg/20 mg, and 10 mg/40 mg.

Contraindications


  • Do not coadminister aliskiren with angiotensin receptor blockers (ARBs), ACE inhibitors, including Amlodipine and Benazepril hydrochloride capsules in patients with diabetes.
  • Amlodipine and Benazepril hydrochloride capsules  are contraindicated in patients with a history of angioedema, with or without previous ACE inhibitor treatment, or patients who are hypersensitive to benazepril, to any other ACE inhibitor, to amlodipine, or to any of the excipients of Amlodipine and Benazepril hydrochloride capsules.
  • Amlodipine and Benazepril hydrochloride capsules are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Amlodipine and Benazepril hydrochloride capsules within 36 hours of switching to or from a neprilysin inhibitor, e.g., sacubitril/valsartan (see Warnings and Precautions 5.1)

Use in specific populations

Pregnancy


Teratogenic Effects

Pregnancy Category D

Use of drugs that act on the RAS during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Amlodipine and Benazepril hydrochloride as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the RAS from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the RAS for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Amlodipine and Benazepril hydrochloride, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Amlodipine and Benazepril hydrochloride for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4)].

Labor and Delivery


The effect of Amlodipine and Benazepril hydrochloride on labor and delivery has not been studied.

Nursing Mothers


Minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril, so that a newborn child ingesting nothing but breast milk would receive less than 0.1% of the maternal doses of benazepril and benazeprilat.

It is not known whether amlodipine is excreted in human milk. Nursing or drug should be discontinued.

Pediatric Use


Neonates with a History of in utero Exposure to Amlodipine and Benazepril hydrochloride

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Benazepril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means; there are occasional reports of benefit from these maneuvers, but experience is limited.

Geriatric Use

In geriatric patients, exposure to amlodipine is increased, thus consider lower initial doses of Amlodipine and Benazepril hydrochloride [see Clinical Pharmacology (12.3)].

Of the total number of patients who received Amlodipine and Benazepril hydrochloride in U.S. clinical studies of Amlodipine and Benazepril hydrochloride, over 19% were 65 years or older while about 2% were 75 years or older. Overall differences in effectiveness or safety were not observed between these patients and younger patients. Clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment

Exposure to amlodipine is increased in patients with hepatic insufficiency, thus consider using lower doses of Amlodipine and Benazepril hydrochloride [see Clinical Pharmacology (12.3)].

Renal Impairment

In patients with severe renal impairment systemic exposure to benazepril is increased. The recommended dose of benazepril in this subgroup is 5 mg which is not an available strength with Amlodipine and Benazepril hydrochloride. Amlodipine and Benazepril hydrochloride is not recommended in patients with severe renal impairment. No dose adjustment of Amlodipine and Benazepril hydrochloride is needed in patients with mild or moderate impairment of renal function [see Dosage and Administration (2.2), Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

Amlodipine and Benazepril Description

Amlodipine and Benazepril hydrochloride capsules USP are a combination of amlodipine besylate and benazepril hydrochloride.


Benazepril hydrochloride USP is a white to off-white, crystalline powder, soluble (greater than 100 mg/mL) in water, in ethanol, and in methanol. Benazepril hydrochloride’s chemical name is 3-[[1-(ethoxycarbonyl)-3-phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-(3S)-benzazepine-1-acetic acid monohydrochloride; its structural formula is:
 

                              


Its molecular formula is C24H28N2O5•HCl, and its molecular weight is 460.96.


Benazeprilat, the active metabolite of benazepril, is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Benazepril is converted to benazeprilat by hepatic cleavage of the ester group.


Amlodipine besylate USP is a white or almost white powder, slightly soluble in water and sparingly soluble in ethanol. Its chemical name is (R,S)3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4­-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulfonate; its structural formula is:
 



Its molecular formula is C20H25ClN2O5•C6H6O3S, and its molecular weight is 567.1.


Amlodipine besylate is the besylate salt of amlodipine, a dihydropyridine calcium channel blocker.


Amlodipine and Benazepril hydrochloride capsules USP are formulated in 6 different strengths for oral administration with a combination of amlodipine besylate equivalent to  2.5 mg, 5 mg or 10 mg of amlodipine, with 10 mg, 20 mg or 40 mg of benazepril hydrochloride providing for the following available combinations: 2.5 mg/10 mg, 5 mg/10 mg, 5 mg/20 mg, 5 mg/40 mg, 10 mg/20 mg, and 10 mg/40 mg.


The inactive ingredients of the capsules are colloidal silicon dioxide, crospovidone, gelatin, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, and titanium dioxide. In addition, the hard gelatin capsule shells of 5 mg/10 mg contains iron oxide black, iron oxide red, and iron oxide yellow, 5 mg/20 mg contains iron oxide red, 5 mg/40 mg and 10 mg/40 mg contains FD&C Blue 1, FD&C Red 3, and 10 mg/20 mg contains D&C Red 28, FD&C Blue 1, FD&C Red 40, and FD&C Yellow 5. The capsules are printed with edible ink containing black iron oxide and shellac.

Amlodipine and Benazepril - Clinical Pharmacology

Mechanism of Action


Benazepril
 
Benazepril and benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and in animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.

Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion.  The latter decrease may result in a small increase of serum potassium. Hypertensive patients treated with benazepril and amlodipine for up to 56 weeks had elevations of serum potassium up to 0.2 mEq/L [see Warnings and Precautions (5.8)].

Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. In animal studies, benazepril had no inhibitory effect on the vasopressor response to angiotensin II and did not interfere with the hemodynamic effects of the autonomic neurotransmitters acetylcholine, epinephrine, and norepinephrine.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Amlodipine and Benazepril hydrochloride remains to be elucidated.

While the mechanism through which benazepril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin aldosterone system, benazepril has an antihypertensive effect even in patients with low-renin hypertension.

Amlodipine
 
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

Pharmacodynamics


Benazepril 

Single and multiple doses of 10 mg or more of benazepril cause inhibition of plasma ACE activity by at least 80% to 90% for at least 24 hours after dosing. For up to 4 hours after a 10 mg dose, pressor responses to exogenous angiotensin I were inhibited by 60% to 90%.

Administration of benazepril to patients with mild-to-moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent, with no compensatory tachycardia. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt and/or volume depleted [see Warnings and Precautions (5.4)].

The antihypertensive effects of benazepril were not appreciably different in patients receiving high- or low-sodium diets.

In normal human volunteers, single doses of benazepril caused an increase in renal blood flow but had no effect on glomerular filtration rate.

Amlodipine

Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing.

With chronic once-daily administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105 to 114 mmHg) had about 50% greater response than patients with mild hypertension (diastolic pressure 90 to 104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressure (+1/-2 mmHg).

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria.

As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume. In hemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and humans, even when coadministered with beta blockers to humans.

Amlodipine does not change sinoatrial (SA) nodal function or atrioventricular (AV) conduction in intact animals or humans. In clinical studies in which amlodipine was administered in combination with beta blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed.

Amlodipine has demonstrated beneficial clinical effects in patients with chronic stable angina, vasospastic angina and angiographically documented coronary artery disease.

Pharmacokinetics

The rate and extent of absorption of benazepril and amlodipine from Amlodipine and Benazepril hydrochloride are the same as when administered as individual tablets. Absorption from the individual tablets is not influenced by the presence of food in the gastrointestinal tract; food effects on absorption from Amlodipine and Benazepril hydrochloride have not been studied.

Absorption:  Following oral administration of Amlodipine and Benazepril hydrochloride, peak plasma concentrations of amlodipine are reached in 6 to 12 hours. Absolute bioavailability has been calculated as between 64% and 90%. Following oral administration of Amlodipine and Benazepril hydrochloride, the peak plasma concentrations of benazepril are reached in 0.5 to 2 hours. The cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat, which reaches peak plasma concentrations in 1.5 to 4 hours. The extent of absorption of benazepril is at least 37%. Amlodipine and Benazepril exhibit dose proportional pharmacokinetics between the therapeutic dose range of 2.5 and 10 mg and 10 and 20 mg, respectively.

Distribution:  The apparent volume of distribution of amlodipine is about 21 L/kg. In vitro studies indicate that approximately 93% of circulating amlodipine is bound to plasma proteins in hypertensive patients. The apparent volume of distribution of benazeprilat is about 0.7 L/kg. Approximately 93% of circulating amlodipine is bound to plasma proteins, and the bound fraction of benazeprilat is slightly higher. On the basis of in vitro studies, benazeprilat’s degree of protein binding should be unaffected by age, by hepatic dysfunction, orover the therapeutic concentration rangeby concentration.

Metabolism:  Amlodipine is extensively (approximately 90%) metabolized in the liver to inactive metabolites. Benazepril is extensively metabolized to form benazeprilat as the main metabolite, which occurs by enzymatic hydrolysis, mainly in the liver. Two minor metabolites are the acyl glucuronide conjugates of benazepril and benazeprilat.

Elimination:  Amlodipine elimination from plasma is biphasic with a terminal elimination half-life of approximately 30 to 50 hours. Steady-state plasma levels are reached after once-daily dosing for 7 to 8 days. Ten percent of unchanged drug and 60% of amlodipine metabolites are excreted in urine. Effective elimination half-life of amlodipine is 2 days. Benazepril is eliminated mainly by metabolic clearance. Benazeprilat is eliminated via the kidneys and the bile; renal excretion is the main route in patients with normal renal function. In the urine, benazepril accounts for less than 1 % and benazeprilat for about 20 % of an oral dose. Elimination of benazeprilat is biphasic with an initial half-life of about 3 hours and a terminal half-life of about 22 hours. Benazeprilat’s effective elimination half-life is 10 to 11 hours, while that of amlodipine is about 2 days, so steady-state levels of the 2 components are achieved after about a week of once-daily dosing.

Special Populations

Geriatric Patients:  No specific clinical studies were performed to understand the impact of age on the pharmacokinetics of Amlodipine and Benazepril as fixed dose combination. As individual component amlodipine is extensively metabolized in the liver. In the elderly, clearance of amlodipine is decreased with resulting increases in peak plasma levels, elimination half-life and area-under-the-plasma-concentration curve [see Use in Specific Populations (8.5)].

Hepatic Impairment:  Patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40 to 60%. Pharmacokinetics of benazepril is not significantly influenced by hepatic impairment [see Use in Specific Populations (8.6)].

Renal Impairment:  The disposition of benazepril and benazeprilat in patients with mild-to-moderate renal insufficiency (CrCl greater than 30 mL/min) is similar to that in patients with normal renal function. In patients with CrCl less than or equal to 30 mL/min, peak benazeprilat levels and the effective half-life increase, resulting in higher systemic exposures. Pharmacokinetics of amlodipine is not significantly influenced by renal impairment [see Dosage and Administration (2.2), Use in Specific Populations (8.7) and Warnings and Precautions (5.7)].

Drug Interactions

Amlodipine

In vitro data in human plasma indicate that amlodipine has no effect on the protein binding of digoxin, phenytoin, warfarin, and indomethacin.

Cimetidine:  Coadministration of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine.

Grapefruit juice: Coadministration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.

Maalox® (antacid): Coadministration of the antacid Maalox with a single dose of amlodipine had no significant effect on the pharmacokinetics of amlodipine.

Sildenafil: A single 100 mg dose of sildenafil in subjects with essential hypertension had no effect on the pharmacokinetic parameters of amlodipine. When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.

Atorvastatin: Coadministration of multiple 10 mg doses of amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.

Digoxin: Coadministration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.

Ethanol (alcohol): Single and multiple 10 mg doses of amlodipine had no significant effect on the pharmacokinetics of ethanol.

Warfarin: Coadministration of amlodipine with warfarin did not change the warfarin prothrombin response time.

Simvastatin: Coadministration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone.

CYP3A Inhibitors: Coadministration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. Erythromycin coadministration in healthy volunteers did not significantly change amlodipine systemic exposure. However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent.

Benazepril

The pharmacokinetic properties of benazepril are not affected by hydrochlorothiazide, furosemide, chlorthalidone, digoxin, propranolol, atenolol, nifedipine, amlodipine, naproxen, acetylsalicylic acid, or cimetidine. Likewise the administration of benazepril does not substantially affect the pharmacokinetics of these medications.

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 5 mg/40 mg (100 Capsules Bottle)


NDC 65862-585-01
Rx only
Amlodipine and
Benazepril
Hydrochloride
Capsules USP 
5 mg*/40 mg
AUROBINDO               100 Capsules




Pharmacologic Category

  • Angiotensin-Converting Enzyme (ACE) Inhibitor
  • Antianginal Agent
  • Antihypertensive
  • Calcium Channel Blocker
  • Calcium Channel Blocker, Dihydropyridine

Dosing Renal Impairment

CrCl >30 mL/minute: No dosage adjustment necessary.

CrCl ≤30 mL/minute: Use is not recommended.

Adverse Reactions

See individual agents.

For Healthcare Professionals

Applies to amlodipine / benazepril: oral capsule

General

The most common side effects were cough, headache, dizziness, and edema.[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness
Frequency not reported: Tremor

Amlodipine:
Common (1% to 10%): Headache, dizziness
Postmarketing reports: Dysgeusia, hypoesthesia, paresthesia, syncope, peripheral neuropathy, hypertonia

Benazepril:
Common (1% to 10%): Headache, dizziness
Postmarketing reports: Paresthesia, dysgeusia[Ref]

Respiratory

Common (1% to 10%): Cough
Frequency not reported: Pharyngitis

Amlodipine:
Uncommon (0.1% to 1%): Cough
Postmarketing reports: Rhinitis

Benazepril:
Common (1% to 10%): Cough[Ref]

Other

Common (1% to 10%): Edema
Frequency not reported: Asthenia, fatigue

Amlodipine:
Common (1% to 10%): Edema
Postmarketing reports: Malaise

Benazepril:
Uncommon (0.1% to 1%): Edema[Ref]

Amlodipine-induced peripheral edema is dose dependent. Benazepril reduces the incidence of edema when added to amlodipine.[Ref]

Genitourinary

Frequency not reported: Impotence, polyuria

Amlodipine:
Postmarketing reports: Micturition disorder, nocturia, erectile dysfunction[Ref]

Gastrointestinal

Frequency not reported: Dry mouth, nausea, abdominal pain, constipation, diarrhea, dyspepsia, esophagitis

Amlodipine:
Postmarketing reports: Gingival hyperplasia, gastritis[Ref]

Musculoskeletal

Frequency not reported: Back pain, musculoskeletal pain, cramps, muscle cramps

Amlodipine:
Postmarketing reports: Muscle spasms, arthralgia

Benazepril:
Postmarketing reports: Arthralgia, arthritis, myalgia[Ref]

Dermatologic

Frequency not reported: Rash, skin nodule, dermatitis

Amlodipine:
Postmarketing reports: Hyperhidrosis, pruritus, skin discoloration, urticaria, erythema multiform

Benazepril:
Postmarketing reports: Stevens-Johnson syndrome, pemphigus, pruritus, photosensitivity reaction[Ref]

Psychiatric

Frequency not reported: Insomnia, nervousness, anxiety, libido decreased[Ref]

Cardiovascular

Frequency not reported: Flushing, hot flashes

Amlodipine:
Postmarketing reports: Tachycardia, hypotension, vasculitis

Benazepril:
Postmarketing reports: Orthostatic symptoms, hypotension, angina pectoris, arrhythmia[Ref]

Ocular

Amlodipine:
Postmarketing reports: Visual impairment, diplopia

Benazepril:
Postmarketing reports: Impaired vision[Ref]

Metabolic

Frequency not reported: Hypokalemia

Amlodipine:
Postmarketing reports: Hyperglycemia, weight decrease or gain[Ref]

Immunologic

Amlodipine:
Postmarketing reports: Allergic reaction[Ref]

Renal

Benazepril
Postmarketing reports: Serum creatinine increased, BUN increased, renal impairment[Ref]

Hematologic

Frequency not reported: Neutropenia

Amlodipine:
Postmarketing reports: Leucocytopenia

Benazepril:
Postmarketing reports: Hemolytic anemia, thrombocytopenia, agranulocytosis, neutropenia[Ref]

Hepatic

Amlodipine:
Postmarketing reports: Jaundice, hepatic enzyme elevations

Benazepril:
Postmarketing reports: Pancreatitis[Ref]

Some side effects of amlodipine / benazepril may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Liver Dose Adjustments

Dose adjustment(s) may be required; however, no specific guidelines have been suggested. Caution recommended.

Precautions

US BOXED WARNING:
-FETAL TOXICITY: If pregnancy is detected, discontinue this drug as soon as possible. Drugs that act directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Other Comments

Monitoring:
-Assess renal function and serum electrolytes prior to initiating therapy and periodically during treatment.
-Monitor congestive heart failure patients closely for the first 2 weeks of treatment with this drug and following a dose increase of this drug or a concomitant diuretic.

Patient advice:
-Females of childbearing age should be informed of the consequences of exposure to this drug during pregnancy; ask these patients to report pregnancies as soon as possible.
-Advise patients to immediately report any signs or symptoms of angioedema (breathing difficulty or swelling of face, eyes, lips, or tongue) and to stop taking this drug until consulting a physician.

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