WARNING: FETAL TOXICITY
id: 5238bbd7-0681-4cdf-adff-d5f48e3b2362
displayName: BOXED WARNING SECTION
FDA Article Code: 34066-1
When pregnancy is detected, discontinue Benazepril HCl and Hydrochlorothiazide as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity
DESCRIPTION
id: e91ae0d6-024f-41fb-af2c-6b4f4b374efa
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Benazepril hydrochloride USP is a white to off-white crystalline powder, soluble (>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 empirical formula is C
24
H
28
N
2
O
5
·HCl, and its molecular weight is 460.96.
Benazeprilat, the active metabolite of benazepril, is a nonsulfhydryl angiotensin-converting enzyme inhibitor. Benazepril is converted to benazeprilat by hepatic cleavage of the ester group.
Hydrochlorothiazide USP is a white, or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n-butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide’s chemical name is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; its structural formula is
Its empirical formula is C
7
H
8
ClN
3
O
4
S
2
, and its molecular weight is 297.73. Hydrochlorothiazide is a thiazide diuretic.
Benazepril HCl and Hydrochlorothiazide is a combination of benazepril and hydrochlorothiazide USP. The tablets are formulated for oral administration with a combination of 10 or 20 mg of benazepril and 12.5 or 25 mg of hydrochlorothiazide USP. The inactive ingredients of the tablets are cellulose compounds, crospovidone, hydrogenated castor oil, iron oxides (10/12.5-mg, 20/12.5-mg, and 20/25-mg tablets), lactose, polyethylene glycol, talc, and titanium dioxide.
INDICATIONS AND USAGE
id: 4d497023-efcb-4698-93c7-2ab11862a539
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Benazepril HCl and Hydrochlorothiazide is indicated for the treatment of hypertension.
This fixed combination drug is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION).
CONTRAINDICATIONS
id: 42681bbf-db68-4021-b815-d86f2ef593a8
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Benazepril HCl and Hydrochlorothiazide is contraindicated in patients who are anuric.
Benazepril HCl and Hydrochlorothiazide is also contraindicated in patients who are hypersensitive to benazepril, to any other ACE inhibitor, to hydrochlorothiazide, or to other sulfonamide-derived drugs. Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma.
Benazepril HCl and Hydrochlorothiazide is also contraindicated in patients with a history of angioedema with or without previous ACE inhibitor treatment.
Benazepril HCl and Hydrochlorothiazide is contraindicated in combination with a neprilysin (e.g., sacubitril). Do not administer Benazepril HCl and Hydrochlorothiazide within 36 hours of switching to or from sacubitril/valsartan a neprilysin inhibitor (see WARNINGS and PRECAUTIONS).
Do not co-administer aliskiren with angiotensin receptor blockers, ACE inhibitors, including Benazepril HCl and Hydrochlorothiazide in patients with diabetes.
ADVERSE REACTIONS
id: d5cf65c9-e444-49dc-bc7f-d3b47457b0de
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Benazepril HCl and Hydrochlorothiazide has been evaluated for safety in over 2500 patients with hypertension; over 500 of these patients were treated for at least 6 months, and over 200 were treated for more than 1 year.
The reported side effects were generally mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects was required in approximately 7% of U.S. patients treated with Benazepril HCl and Hydrochlorothiazide and in 4% of patients treated with placebo.
The most common reasons for discontinuation of therapy with Benazepril HCl and Hydrochlorothiazide in U.S. studies were cough (1.0%; see PRECAUTIONS), “dizziness” (1.0%), headache (0.6%), and fatigue (0.6%).
The side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with Benazepril HCl and Hydrochlorothiazide are shown in the table below.
|
Reactions Possibly or Probably Drug-Related
Patients in U.S. Placebo-Controlled Studies |
|
Benazepril HCl and Hydrochlorothiazide
N = 665
|
Placebo
N = 235
|
|
N |
% |
N |
% |
| “Dizziness” |
41 |
6.3 |
8 |
3.4 |
| Fatigue |
34 |
5.2 |
6 |
2.6 |
| Postural Dizziness |
23 |
3.5 |
1 |
0.4 |
| Headache |
20 |
3.1 |
10 |
4.3 |
| Cough |
14 |
2.1 |
3 |
1.3 |
| Hypertonia |
10 |
1.5 |
3 |
1.3 |
| Vertigo |
10 |
1.5 |
2 |
0.9 |
| Nausea |
9 |
1.4 |
2 |
0.9 |
| Impotence |
8 |
1.2 |
0 |
0.0 |
| Somnolence |
8 |
1.2 |
1 |
0.4 |
Other side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in 0.3% to 1.0% of patients treated with Benazepril HCl and Hydrochlorothiazide were the following:
Cardiovascular:Palpitations, flushing.
Gastrointestinal:Vomiting, diarrhea, dyspepsia, anorexia, and constipation.
Neurologic and Psychiatric:Insomnia, nervousness, paresthesia, libido decrease, dry mouth, taste perversion, and tinnitus.
Dermatologic:Rash and sweating.
Other:Urinary frequency, arthralgia, myalgia, asthenia, and pain (including chest pain and abdominal pain).
Other adverse experiences reported in 0.3% or more of Benazepril HCL and Hydrochlorothiazide patients in U.S. controlled clinical trials, and rarer events seen in post-marketing experience, were the following; asterisked entries occurred in more than 1% of patients (in some, a causal relationship to Benazepril HCl and Hydrochlorothiazide is uncertain):
Cardiovascular:Syncope, peripheral vascular disorder, and tachycardia.
Body as a Whole:Infection, back pain*, flu syndrome*, fever, chills, and neck pain.
Dermatologic: Photosensitivity and pruritus.
Gastrointestinal:Gastroenteritis, flatulence, and tooth disorder.
Neurologic and Psychiatric:Hypesthesia, abnormal vision, abnormal dreams, and retinal disorder.
Respiratory:Upper respiratory infection*, epistaxis, bronchitis, rhinitis*, sinusitis*, and voice alteration.
Other:Conjunctivitis, arthritis, urinary tract infection, alopecia, and urinary frequency*.
Post-Marketing Experience
The following adverse reactions have been identified during post-approval use of either benazepril or hydrochlorothiazide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure:
Benazepril: Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pemphigus, and thrombocytopenia, eosinophilic pneumonitis.
Hydrochlorothiazide
Digestive: Pancreatitis, small bowel angioedema, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia.
Neurologic:Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.
Musculoskeletal:Muscle spasm.
Hematologic:Aplastic anemia, agranulocytosis, leukopenia, neutropenia, and thrombocytopenia.
Metabolic:Hyperglycemia, glycosuria, hyperuricemia, pyrexia, asthenia, parathyroid gland changes with hypercalcemia and hypophosphatemia.
Hypersensitivity:Anaphylactoid reactions, necrotizing angiitis, respiratory distress (including pneumonitis and pulmonary edema), purpura, urticaria, rash, and photosensitivity.
Skin: Erythema multiforme including Stevens-Johnson syndrome, and exfoliative dermatitis including toxic epidermal necrolysis.
OVERDOSAGE
id: 85d3bf58-ca0c-4f1f-bc99-351ecb7171d4
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
No specific information is available on the treatment of overdosage with Benazepril HCl and Hydrochlorothiazide; treatment should be symptomatic and supportive. Therapy with Benazepril HCl and Hydrochlorothiazide should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.
Single oral doses of 1 g/kg of benazepril caused reduced activity in mice, and doses of 3 g/kg were associated with significant lethality. Reduction of activity in rats was not seen until they had received doses of 5 g/kg, and doses of 6 g/kg were not lethal. In single-dose studies of hydrochlorothiazide, most rats survived doses up to 2.75 g/kg.
Data from human overdoses of benazepril are scanty, but the most common manifestation of human benazepril overdosage is likely to be hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
Laboratory determinations of serum levels of benazepril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of benazepril overdose.
No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of benazepril and its metabolites. Benazeprilat is only slightly dialyzable, but dialysis might be considered in overdosed patients with severely impaired renal function (see WARNINGS).
Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of benazepril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of benazepril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat benazepril overdose by infusion of normal saline solution.
DOSAGE AND ADMINISTRATION
id: ae3936bc-a659-4602-8bf6-c73912004206
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Dose once daily. The dosage may then be increased after 2-3 weeks as needed to help achieve blood pressure goals. The maximum recommended dose is 20mg/25mg.
Switch Therapy: A patient whose blood pressure is not adequately controlled with benazepril alone or with hydrochlorothiazide alone may be switched to combination therapy with Benazepril HCl and Hydrochlorothiazide. The usual recommended starting dose is 10/12.5 mg once daily to control blood pressure.
Replacement Therapy:The combination may be substituted for the titrated individual components.
HOW SUPPLIED
id: c29fb745-876c-4f23-aceb-432988e93433
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Benazepril HCl USP and Hydrochlorothiazide USP is available in tablets of three different strengths:
|
Benazepril HCl
|
Hydrochlorothiazide
|
Tablet Color
|
| 10 mg |
12.5 mg |
light pink |
| 20 mg |
12.5 mg |
grayish-violet |
| 20 mg |
25 mg |
red |
Tablets of each strength are supplied in bottles that contain a desiccant and 100 tablets.
The National Drug Codes for the various packages are:
|
Dose
|
Bottle of 100
|
Tablet Imprint
|
| 10/12.5 |
NDC 64980-194-01 |
452 |
| 20/12.5 |
NDC 64980-195-01 |
453 |
| 20/25 |
NDC 64980-196-01 |
454 |
Tablets are oblong and scored, with “LOTENSIN HCT” on one side and appropriate number imprinted on the other side.
Storage: Do not store above 86ºF (30ºC). Protect from moisture and light. Dispense in tight, light
-resistant container (USP).
Distributed by:
Rising Pharmaceuticals, Inc.
Saddle Brook, NJ 07663
Manufactured for:
Validus Pharmaceuticals LLC
Parsippany, NJ 07054
© 2017 Validus Pharmaceuticals LLC
60064-01 August 2017
PRINCIPAL DISPLAY PANEL 10/12.5 Package Label
id: ccd8fa10-35ee-43c0-8902-c84a7878a3ad
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Rising® NDC 64980-194-01
Benazepril HCl and
Hydrochlorothiazide USP
10/12.5 mg
100 Tablets Rx only
PRINCIPAL DISPLAY PANEL 20/12.5 Package Label
id: 10b2335f-3e14-4358-8ad3-ec5736504be2
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Rising® NDC 64980-195-01
Benazepril HCl and
Hydrochlorothiazide USP
20/12.5 mg
100 Tablets Rx only
PRINCIPAL DISPLAY PANEL 20/25 Package Label
id: 15da04b0-6c5d-40e1-ad64-0ada4f97c380
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Rising® NDC 64980-196-01
Benazepril HCl and
Hydrochlorothiazide USP
20/25 mg
100 Tablets Rx only
