AMLODIPINE BESYLATE AND BENAZEPRIL HYDROCHLORIDE capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

AMLODIPINE BESYLATE (UNII: 864V2Q084H) (AMLODIPINE - UNII:1J444QC288), BENAZEPRIL HYDROCHLORIDE (UNII: N1SN99T69T) (BENAZEPRILAT - UNII:JRM708L703)

Available from:

Lupin Pharmaceuticals, Inc.

INN (International Name):

AMLODIPINE BESYLATE

Composition:

AMLODIPINE 2.5 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Amlodipine and benazepril hydrochloride capsules are indicated for the treatment of hypertension in patients not adequately controlled on monotherapy with either agent. - Do not coadminister aliskiren with angiotensin receptor blockers (ARBs), ACE inhibitors, including amlodipine and benazepril hydrochloride in patients with diabetes. - Amlodipine and benazepril hydrochloride is 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 is 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)] . Risk Summary Amlodipine and benazepril hydrochloride capsules can cause fetal harm when administered to a pregnant woman. 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. 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. When pregnancy is detected, discontinue amlodipine and benazepril hydrochloride capsules as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to amlodipine and benazepril hydrochloride for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to amlodipine and benazepril hydrochloride, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data Benazepril and Amlodipine: 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 twice the amlodipine dose delivered when the maximum recommended dose of amlodipine and benazepril hydrochloride capsules is given to a 60 kg patient. Similarly, the 5 mg/kg/day dose of benazepril is approximately equivalent with the benazepril dose delivered when the maximum recommended dose of amlodipine and benazepril hydrochloride capsules is given to a 60 kg patient. 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 (12 times the MRHD on a body surface area basis, assuming a 60 kg patient). Rabbits received doses of up to 1.5:0.75 mg/kg/day (equivalent to the maximum recommended dose of amlodipine and benazepril hydrochloride capsules given to a 60 kg patient). Risk Summary 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. Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine or benazepril on milk production. Safety and effectiveness in pediatric patients have not been established. 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. Exposure to amlodipine is increased in patients with hepatic insufficiency, thus consider using lower doses of amlodipine and benazepril hydrochloride capsules [see Clinical Pharmacology (12.3)] . 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 capsules. Amlodipine and benazepril hydrochloride capsules are not recommended in patients with severe renal impairment. No dose adjustment of amlodipine and benazepril hydrochloride capsules 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)] .

Product summary:

Amlodipine and benazepril hydrochloride capsules USP are available as capsules containing 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. Amlodipine and benazepril hydrochloride capsules USP, 2.5 mg/10 mg are size '2' capsules with white opaque cap and white opaque body, imprinted with 'LU' (in black ink) on cap and 'E11' (in black ink) on body, containing white to off-white powder and white to off-white, circular tablet, debossed with '1' on one side and plain on the other side. NDC 68180-755-01    Bottles of 100 capsules NDC 68180-755-02    Bottles of 500 capsules               NDC 68180-755-03    Bottles of 1000 capsules Amlodipine and benazepril hydrochloride capsules USP, 5 mg/10 mg are size '2' capsules with yellow opaque cap and yellow opaque body, imprinted with 'LU' (in black ink) on cap and 'E12' (in black ink) on body, containing white to off-white powder and white to off-white, circular tablet, debossed with '1' on one side and plain on the other side. NDC 68180-756-01    Bottles of 100 capsules NDC 68180-756-02    Bottles of 500 capsules NDC 68180-756-03    Bottles of 1000 capsules Amlodipine and benazepril hydrochloride capsules USP, 5 mg/20 mg are size '2' capsules with flesh opaque cap and flesh opaque body, imprinted with 'LU' (in black ink) on cap and 'E13' (in black ink) on body, containing white to off-white powder and white to off-white, circular tablet, plain on both sides. NDC 68180-459-01    Bottles of 100 capsules NDC 68180-459-02    Bottles of 500 capsules NDC 68180-459-03    Bottles of 1000 capsules Amlodipine and benazepril hydrochloride capsules USP, 5 mg/40 mg are size '2' capsules with dark green cap and white body, imprinted with 'LU' (in black ink) on cap and 'E15' (in black ink) on body, containing white to off-white powder and two white to off-white, circular tablets, plain on both sides. NDC 68180-463-01    Bottles of 100 capsules NDC 68180-463-02    Bottles of 500 capsules NDC 68180-463-03    Bottles of 1000 capsules Amlodipine and benazepril hydrochloride capsules USP, 10 mg/20 mg are size '2' capsules with brown cap and brown body, imprinted with 'LU' (in black ink) on cap and 'E14' (in black ink) on body, containing white to off-white powder and white to off-white, circular tablet, plain on both sides. NDC 68180-472-01    Bottles of 100 capsules NDC 68180-472-02    Bottles of 500 capsules NDC 68180-472-03    Bottles of 1000 capsules Amlodipine and benazepril hydrochloride capsules USP, 10 mg/40 mg are size '2' capsules with dark blue cap and white body, imprinted with 'LU' (in black ink) on cap and 'E16' (in black ink) on body, containing white to off-white powder and two white to off-white, circular tablets, plain on both sides. NDC 68180-473-01    Bottles of 100 capsules NDC 68180-473-02    Bottles of 500 capsules NDC 68180-473-03    Bottles of 1000 capsules Storage : Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature.] Protect from moisture. Dispense in tight container (USP).  

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

HYDROCHLORIDE CAPSULE
Lupin Pharmaceuticals, Inc.
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Patient Information
AMLODIPINE AND BENAZEPRIL HYDROCHLORIDE CAPSULES USP
(am loe′ di peen and ben az′ e pril hye′′ droe klor′ ide)
Read this Patient Information leaflet before you start taking
amlodipine and benazepril hydrochloride
capsules and each time you get a refill. There may be new information.
This leaflet does not replace talking
with your doctor. If you have any questions, ask your doctor or
pharmacist.
What is the most important information I should know about amlodipine
and benazepril hydrochloride
capsules?
•
Amlodipine and benazepril hydrochloride capsules can cause harm or
death to an unborn baby.
•
Talk to your doctor about other ways to lower your blood pressure if
you plan to become pregnant.
•
If you get pregnant while taking amlodipine and benazepril
hydrochloride capsules, tell your doctor
right away.
What is amlodipine and benazepril hydrochloride capsule?
Amlodipine and benazepril hydrochloride capsule contains 2
prescription medicines that work together to
lower blood pressure: amlodipine besylate (the active ingredient found
in Norvasc®), a calcium channel
blocker, and benazepril hydrochloride (Lotensin®), an ACE inhibitor.
Your doctor will prescribe amlodipine
and benazepril hydrochloride capsules only after other medicines
haven't worked.
High Blood Pressure (hypertension).Blood pressure is the force of
blood in your blood vessels. You have
high blood pressure when the force is too much. Amlodipine and
benazepril hydrochloride capsules can help
your blood vessels relax so your blood pressure is lower.
Amlodipine and benazepril hydrochloride capsules have not been studied
in children.
Who should not take amlodipine and benazepril hydrochloride capsules?
Don't take amlodipine and benazepril hydrochloride capsules if you are
allergic to any of the ingredients.
There is a complete list at the end of this leaflet.
What should I tell my Doctor before taking amlodipine and benazepril
hydrochloride capsules?
Tell yo

Summary of Product characteristics

AMLODIPINE BESYLATE AND BENAZEPRIL HYDROCHLORIDE- AMLODIPINE
BESYLATE AND BENAZEPRIL HYDROCHLORIDE CAPSULE
LUPIN PHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
AMLODIPINE AND
BENAZEPRIL HYDROCHLORIDE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING
INFORMATION FOR AMLODIPINE AND BENAZEPRIL HYDROCHLORIDE CAPSULES.
AMLODIPINE AND BENAZEPRIL HYDROCHLORIDE CAPSULES, FOR ORAL USE.
INITIAL U.S. APPROVAL: 1995
WARNING: FETAL TOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
WHEN PREGNANCY IS DETECTED, DISCONTINUE AMLODIPINE AND BENAZEPRIL
HYDROCHLORIDE
CAPSULES AS SOON AS POSSIBLE (5.5).
DRUGS THAT ACT DIRECTLY ON THE RENIN-ANGIOTENSIN SYSTEM (RAS) CAN
CAUSE INJURY AND
DEATH TO THE DEVELOPING FETUS (5.5)
INDICATIONS AND USAGE
Amlodipine and benazepril hydrochloride capsule, is a combination
capsule of amlodipine, a
dihydropyridine calcium channel blocker (DHP CCB) and benazepril, an
angiotensin converting-enzyme
(ACE) inhibitor. Amlodipine and benazepril hydrochloride capsule, is
indicated for the treatment of
hypertension in patients not adequately controlled on monotherapy with
either agent (1).
DOSAGE AND ADMINISTRATION
Usual starting dose is 2.5/10 mg. (2.1)
May be used as add-on therapy for patients not adequately controlled
with either a dihydropyridine
calcium channel blocker or an ACE inhibitor. (2.2)
Patients who experience edema with amlodipine may be switched to
amlodipine and benazepril
hydrochloride capsules, containing a lower dose of amlodipine. (2.1)
DOSAGE FORMS AND STRENGTHS
Capsules (amlodipine/benazepril mg): 2.5/10, 5/10, 5/20, 5/40, 10/20,
10/40 (3)
CONTRAINDICATIONS
Do not coadminister aliskiren with ACE inhibitors, including
amlodipine and benazepril hydrochloride, in
patients with diabetes. (4)
Amlodipine and benazepril hydrochloride is contraindicated in patients
with a history of angioedema or
patients who are hypersensitive to benazepril or to amlodipine. (4)
Amlodipine and ben