Lotensin

GENERIC AVAILABLE: Yes

Single oral doses of 3 g/kg benazepril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 6 g/kg. Reduced activity was seen at 1 g/kg in mice and at 5 g/kg in rats. Human overdoses of benazepril have not been reported, but the most common manifestation of human benazepril overdosage is likely to be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Hypotension can be associated with electrolyte disturbances and renal failure.

Benazepril is only slightly dialyzable, but consider dialysis to support patients with severely impaired renal function [see WARNINGS AND PRECAUTIONS].

If ingestion is recent, consider activated charcoal. Consider gastric decontamination (e.g., vomiting, gastric lavage) in the early period after ingestion.

Monitor for blood pressure and clinical symptoms. Supportive management should be employed to ensure adequate hydration and to maintain systemic blood pressure.

In the case of marked hypotension, infuse physiological saline solution; as needed, consider vasopressors (e.g., catecholamines i.v.).

Lotensin is a prescription medicine used with other medications to treat high blood pressure. Lotensin belongs to a group of medications called angiotensin-converting enzyme (ACE) inhibitors. Lotensin works by blocking the ACE enzyme, which helps blood vessels to relax and lowers blood pressure.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamin, and herbal supplements. Especially tell your doctor if you take:

• diuretics 
• potassium-sparing diuretics
• potassium supplements
• lithium (Eskalith, Lithobid)
• NSAIDs
• injectable gold (sodium aurothiomalate)

This is not a complete list of Lotensin drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are breastfeeding or plan to breastfeed. Small amounts of Lotensin may be excreted in human breast milk. The effects are unknown.

If you take too much Lotensin, call your local Poison Control Center or seek emergency medical attention right away.

General

BP Monitoring and Treatment Goals

• Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

• When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

• If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

• Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

• Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

Administer benazepril orally once or twice daily without regard to meals.1

Administer benazepril as extemporaneously prepared oral suspension in pediatric patients unable to swallow tablets or in those for whom the calculated daily dosage does not correspond to the available tablet strengths.1

Preparation of extemporaneous suspension containing benazepril hydrochloride 2 mg/mL: Add 75 mL of suspending vehicle (Ora-Plus) to a polyethylene terephthalate (PET) bottle containing fifteen 20-mg tablets of benazepril hydrochloride; shake the contents for ≥2 minutes.1 Allow concentrated suspension to stand for a minimum of 60 minutes following reconstitution, then shake for a minimum of 1 additional minute.1 Dilute the concentrated suspension with 75 mL of syrup (Ora-Sweet); shake the container to disperse the ingredients.1 Shake suspension before dispensing each dose.1

Dosage

Benazepril is available as benazepril hydrochloride; dosage expressed in terms of the salt.1 11 12

Pediatric Patients

Children ≥6 years of age: Initially, 0.2 mg/kg (up to 10 mg) once daily.1 45 Adjust dosage until the desired BP goal is achieved (up to maximum dosage of 0.6 mg/kg or 40 mg daily).1 45

Adults

Initially, 10 mg once daily in patients not receiving a diuretic.1 4 13

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating benazepril.1 May cautiously resume diuretic therapy if BP not controlled adequately with benazepril alone.1 If diuretic cannot be discontinued, increase sodium intake and give lower initial benazepril hydrochloride dose (5 mg) under close medical supervision.1 13

Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.13

Usual dosage: 20–40 mg daily, given in 1 dose or 2 divided doses.1 13

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering benazepril in 2 divided doses.1 13

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.11

In studies using benazepril/hydrochlorothiazide fixed combination in dosages of benazepril hydrochloride 5–20 mg daily and hydrochlorothiazide 6.25–25 mg daily, BP response increased with increasing dosages of the drugs.11

If BP is not adequately controlled by monotherapy with benazepril, can switch to the fixed-combination preparation containing benazepril hydrochloride 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, benazepril hydrochloride 20 mg and hydrochlorothiazide 12.5 mg.11 Adjust dosage of either or both drugs according to patient’s response.11

If BP is controlled by monotherapy with hydrochlorothiazide 25 mg daily but potassium loss is problematic, can switch to fixed-combination preparation containing benazepril hydrochloride 5 mg and hydrochlorothiazide 6.25 mg.11

If BP is controlled with benazepril and hydrochlorothiazide (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.11

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.12

In studies using benazepril/amlodipine fixed combination in dosages of benazepril hydrochloride 10–40 mg daily and amlodipine 2.5–10 mg daily, BP response increased with increasing amlodipine dosage in all patient groups and increased with increasing benazepril dosage in nonblack patient groups.12

If BP is not adequately controlled by monotherapy with benazepril (or another ACE inhibitor) or amlodipine (or another dihydropyridine-derivative calcium-channel blocker), can switch to benazepril/amlodipine fixed combination.12

If BP is adequately controlled by monotherapy with amlodipine, but edema has developed, can switch to benazepril/amlodipine fixed combination to achieve similar or better BP control without edema.12 May be prudent to reduce amlodipine dosage, especially in nonblack patients, when benazepril is initiated to avoid excessive antihypertensive response.12

If BP is controlled with benazepril and amlodipine (administered separately), can switch to the fixed-combination preparation containing the corresponding individual doses for convenience.12

Adjust dosage of benazepril/amlodipine fixed combination according to patient’s response; consider that steady-state plasma concentrations of benazepril and amlodipine are reached after 2 and 7 days, respectively.12

In small or frail individuals, preparations containing benazepril in fixed combination with 5 or 10 mg of amlodipine exceed the initial recommended dosage (2.5 mg daily) of amlodipine.12

Prescribing Limits

Pediatric Patients

Maximum 0.6 mg/kg or 40 mg of benazepril hydrochloride daily.1 45

Adults

Maximum 80 mg of benazepril hydrochloride daily.1

Special Populations

The following information addresses dosage of benazepril in special populations. Dosages of drugs administered in fixed combination with benazepril also may require adjustment in certain patient populations; the need for such dosage adjustments must be considered in the context of cautions, precautions, and contraindications specific to that population and drug.11 12

Hepatic Impairment

Preparations containing benazepril in fixed combination with 5 or 10 mg of amlodipine exceed the initial recommended dosage of amlodipine (2.5 mg daily) in patients with hepatic impairment.12

Renal Impairment

Initially, benazepril hydrochloride 5 mg once daily in adults with Clcr <30 mL/minute or Scr >3 mg/dL; titrate until BP is controlled or to maximum of 40 mg daily.1 Use of benazepril not recommended in pediatric patients with Clcr <30 mL/minute per 1.73 m2.1 45

Preparations containing benazepril in fixed combination with hydrochlorothiazide are not recommended in patients with Clcr ≤30 mL/minute or Scr >3 mg/dL.11 Loop diuretics are preferred to thiazides in these patients.11

Preparations containing benazepril in fixed combination with amlodipine are not recommended in patients with Clcr ≤30 mL/minute or Scr >3 mg/dL.12

Geriatric Patients

Select dosage of benazepril carefully.1 11 12 (See Geriatric Use under Cautions.)

Preparations containing benazepril in fixed combination with 5 or 10 mg of amlodipine exceed the initial recommended dosage (2.5 mg daily) of amlodipine in geriatric patients.12

Volume- and/or Salt-depleted Patients

Correct volume and/or salt depletion prior to initiation of benazepril therapy or initiate therapy under close medical supervision using lower initial dosage.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In addition to the use of benazepril, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium (salt). Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that this medicine will not cure your high blood pressure but it does help control it. Therefore, you must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

If your child cannot swallow the tablets, an oral liquid may be given. Ask your doctor or pharmacist about this.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults—At first, 10 milligrams (mg) once a day. Your doctor may increase your dose up to 20 to 40 mg per day, taken as a single dose or divided into two doses.
    • Children 6 years of age and older—Dose is based on body weight and must be determined by your doctor. The starting dose is usually 0.2 milligram (mg) per kilogram (kg) of body weight per day. Your doctor may adjust the dose as needed. However, the dose is usually not more than 0.6 mg per kg of body weight or 40 mg per day.
    • Children younger than 6 years of age—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the mixed oral liquid in the refrigerator and store it for up to 30 days. Do not freeze.

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:

• Chills
• cold sweats
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• unusual tiredness or weakness

• Arm, back, or jaw pain
• blistering, peeling, or loosening of the skin
• bloating or swelling of the face, arms, hands, lower legs, or feet
• chest pain or discomfort
• diarrhea
• fast, irregular, pounding, or racing heartbeat or pulse
• feeling of warmth
• fever
• general feeling of tiredness or weakness
• itching
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• nausea
• rapid breathing
• rapid weight gain
• red skin lesions, often with a purple center
• red, irritated eyes
• redness of the face, neck, arms, and occasionally, upper chest
• shortness of breath
• skin rash
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• sweating
• tingling of the hands or feet
• unusual weight gain or loss
• wheezing

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:

• Headache

• Cough
• dizziness
• sleepiness or unusual drowsiness

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.

• It is used to treat high blood pressure.
• It may be given to you for other reasons. Talk with the doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Benazepril hydrochloride, USP is a white to off-white crystalline powder, soluble (> 100 mg/mL) in water, in ethanol, and in methanol. Its chemical name is benazepril 3-[[1-(ethoxy-carbonyl)-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 empirical formula is C24H28N2O5•HCl, and its molecular weight is 460.96.

Benazeprilat, the active metabolite of benazepril, is a non-sulfhydryl angiotensin-converting enzyme inhibitor.

Lotensin is supplied as tablets containing 10 mg, 20 mg, and 40 mg of benazepril hydrochloride for oral administration. The inactive ingredients are colloidal silicon dioxide, crospovidone, hydrogenated castor oil (10 mg and 20 mg tablets), hypromellose, iron oxides, lactose, magnesium stearate (40 mg tablets), microcrystalline cellulose, polysorbate 80, propylene glycol (40 mg tablets), starch, talc, and titanium dioxide.

Hypertension

Adult Patients

In single-dose studies, Lotensin lowered blood pressure within 1 hour, with peak reductions achieved between 2 and 4 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. In multiple-dose studies, once-daily doses of between 20 mg and 80 mg decreased seated pressure 24 hours after dosing by about 6 to 12 mm Hg systolic and 4 to 7 mm Hg diastolic. The trough values represent reductions of about 50% of that seen at peak.

Four dose-response studies using once-daily dosing were conducted in 470 mild-to-moderate hypertensive patients not using diuretics. The minimal effective once-daily dose of Lotensin was 10 mg; but further falls in blood pressure, especially at morning trough, were seen with higher doses in the studied dosing range (10 to 80 mg). In studies comparing the same daily dose of Lotensin given as a single morning dose or as a twice-daily dose, blood pressure reductions at the time of morning trough blood levels were greater with the divided regimen.

The antihypertensive effects of Lotensin 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.

Use of Lotensin in combination with thiazide diuretics gives a blood-pressure-lowering effect greater than that seen with either agent alone. By blocking the renin-angiotensin-aldosterone axis, administration of Lotensin tends to reduce the potassium loss associated with the diuretic.

Pediatric Patients

In a clinical study of 107 pediatric patients, 7 to 16 years of age, with either systolic or diastolic pressure above the 95th percentile, patients were given 0.1 or 0.2 mg/kg then titrated up to 0.3 or 0.6 mg/kg with a maximum dose of 40 mg once daily. After four weeks of treatment, the 85 patients whose blood pressure was reduced on therapy were then randomized to either placebo or benazepril and were followed up for an additional two weeks. At the end of two weeks, blood pressure (both systolic and diastolic) in children withdrawn to placebo rose by 4 to 6 mm Hg more than in children on benazepril. No dose-response was observed.

• Lotensin is a brand (trade) name for benazepril.
• Benazepril inhibits an enzyme called angiotensin-converting enzyme. This enzyme is involved in the production of angiotensin II, a powerful vasoconstrictor (narrows arteries), which also stimulates the release of the hormone aldosterone from the adrenal glands (aldosterone increases blood pressure). By inhibiting this enzyme, benazepril opens up the arteries (vasodilates) and lowers blood pressure.
• Lotensin (benazepril) belongs to a group of medicines known as angiotensin-converting enzyme (ACE) inhibitors.