Generic name: Hydrochlorothiazide, USP and propranolol hydrochloride, USP.

Capozide is a diuretic combination medication that is used to treat high blood pressure and fluid retention. It contains the drugs hydrochlorothiazide and captopril. Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention. Captopril is an ACE inhibitor that relaxes blood vessels, allowing blood to flow more easily. This combination medication is used to treat hypertension (high blood pressure). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This medication may also be used to treat congestive heart failure.

Pharmacokinetics

Capozide is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations of hydrochlorothiazide and captopril are reached in 1-2 hours and 2-4 hours, respectively. The bioavailability of hydrochlorothiazide is approximately 70%. Hydrochlorothiazide crosses the placental but not the blood-brain barrier.

Indications and usage

Capozide is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.

Captopril: Captopril, an ACE inhibitor, is a white, crystalline powder with a molecular weight of 427.0. It is soluble in water and insoluble in ethanol.

Hydrochlorothiazide: Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.7. It is soluble in water and insoluble in ethanol.

Chemically, hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its structural formula is:

Each CAPOZIDE tablet for oral administration contains 25 mg of captopril and 25 mg of hydrochlorothiazide USP. In addition, each tablet contains the following inactive ingredients: anhydrous lactose NF, carnauba wax, colloidal silicon dioxide, crospovidone USP, hypromellose USP2910 3cP, magnesium stearate NF and microcrystalline cellulose NF. Iron oxide red is the color additive in the tablet coating.

Contraindictions

Capozide is contraindicated in patients with:

  • Anuria.
  • Hypersensitivity to any ingredient in this product.

WARNINGS AND PRECAUTIONS

Sulfonamide Hypersensitivity Reactions: CAPOZIDE contains hydrochlorothiazide, a sulfonamide. Some patients with hypersensitivity to other sulfonamide-derived drugs have experienced cross-sensitivity to hydrochlorothiazide.

Fetal Toxicity: Use of drugs that act on the renin-angiotensin system 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 CAPOZIDE 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 renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In animal reproduction studies, administration of ACE inhibitors during pregnancy has been associated with fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, death).

Because of the potential for serious adverse reactions in nursing infants from CAPOZIDE, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

Do not co-administer aliskiren with CAPOZIDE in patients with diabetes. Avoid use of aliskiren with CAPOZIDE in patients with renal impairment (GFR <60 mL/min).

ACE inhibitors can cause hypotension and acute renal insufficiency, especially when used concomitantly with diuretics. Monitor blood pressure and serum creatinine levels closely. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on CAPOZIDE and other agents that affect the RAS.

Excessive Hypotension: CAPOZIDE can cause symptomatic hypotension, particularly in patients with renal impairment (GFR <60 mL/min), or hypovolemia. If hypotension occurs, place the patient in a supine position and, if necessary, give an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment with CAPOZIDE, which usually can be continued without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops after the initial dose of CAPOZIDE and persists for more than 1 hour after administration or requires treatment, a reduction of the dose or discontinuation of treatment may be necessary.

Hyperkalemia: CAPOZIDE can cause hyperkalemia, particularly in patients with renal impairment (GFR <60 mL/min) and diabetes mellitus. Monitor serum potassium levels closely. If hyperkalemia occurs, treatment should be symptomatic and supportive. Severe hyperkalemia may require hemodialysis.

Hypersensitivity Reactions: Hypersensitivity reactions to hydrochlorothiazide may occur in some patients. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. There have been reports of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema. If hypersensitivity reactions occur, discontinue CAPOZIDE and institute appropriate therapy.

Anaphylactoid Reactions During Desensitization: Anaphylactoid reactions during dialysis have occurred in patients treated with ACE inhibitors. These reactions have also been reported in patients receiving prodrugs of ACE inhibitors (angiotensin-converting enzyme inhibitor-related compounds) that are metabolized to ACE inhibitors. There have been reports of angioedema involving the tongue, glottis, or larynx. Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has also been reported. These reactions have been associated with upper respiratory tract swelling, dyspnea, wheezing, and stridor. There has also been one report of death in a patient with severe angioedema after laryngeal manipulation that resulted in airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, CAPOZIDE should be discontinued immediately and appropriate emergency therapy instituted.

Non-Steroidal Anti-inflammatory Agents (NSAIAs): In some patients treated with CAPOZIDE, elevation in BUN or serum creatinine, or both has occurred. These changes are more likely to occur in elderly patients and those with renal impairment. Monitor serum creatinine and BUN levels periodically in patients receiving CAPOZIDE and NSAIAs.

Sarcoidosis: Sarcoidosis, or a similar form of Granulomatous disease, has been reported in association with the use of thiazide diuretics. Discontinue CAPOZIDE if sarcoidosis develops.

Thiazides have been shown to cross the placental barrier and appear in cord blood. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from hydrochlorothiazide. Thiazides should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Dosage and Administration

The recommended initial dose of Capozide is one tablet taken orally twice a day. The dosage may be adjusted upward to a maximum recommended dose of two tablets twice a day as needed to control blood pressure. If blood pressure is not controlled with CAPOZIDE alone, diuretic therapy should be resumed. If additional reduction in blood pressure is required, another antihypertensive agent from a different class may be added.

For patients who cannot tolerate the full blood pressure lowering effect of two CAPOZIDE tablets, a single tablet twice daily may provide adequate control of blood pressure.

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

CAPOZIDE Tablets are available as follows:

25 mg/15 mg Pink, film coated, capsule shaped tablets debossed “WPI” on one side and “3375” on the other. Bottle of 100 NDC 0536-3375-01. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Keep in a tight container. Protect from light and moisture. Dispense in a tight container as defined in the USP/NF.