Captopril And Hydrochlorothiazide

Description

DESCRIPTION Captopril and hydrochlorothiazide tablets, USP for oral administration combines two antihypertensive agents: captopril and hydrochlorothiazide. Captopril, the first of a new class of antihypertensive agents, is a specific competitive inhibitor of angiotensin I-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I to angiotensin II. Hydrochlorothiazide is a benzothiadiazide (thiazide) diuretic-antihypertensive. Captopril, USP is a white to off-white crystalline powder with characteristic sulfide-like odor; it is freely soluble in water, ethanol, methanol, chloroform, isopropyl alcohol and methylene chloride and soluble in ethyl acetate. It dissolves in dilute solution of alkali hydroxide. Hydrochlorothiazide, USP is a white or almost white, almost odorless crystalline powder. Very slightly soluble in water, sparingly soluble in Ethanol and Methanol, soluble in Acetone. Freely soluble in N,N-Dimethylformamide, in n-Butylamine and in diluted solutions of alkali hydroxides. Practically insoluble in Ether, in Chloroform and in diluted mineral acids. Captopril is designated chemically as 1-[(2S)-3-Mercapto-2-methylpropionyl]-L-proline; Hydrochlorothiazide is 6-Chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Their structural formulas are: Captopril and hydrochlorothiazide tablets are available for oral administration in four combinations of captopril with hydrochlorothiazide: 25 mg with 15 mg, 25 mg with 25 mg, 50 mg with 15 mg, and 50 mg with 25 mg. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch (corn) and sodium lauryl sulfate. The 25 mg/25 mg and 50 mg/25 mg tablets also contain FD&C Yellow No. 6 Aluminum Lake. captopril-struct

What Is Captopril And Hydrochlorothiazide Used For?

INDICATIONS & USAGE Captopril and hydrochlorothiazide tablets are indicated for the treatment of hypertension. The blood pressure lowering effects of captopril and thiazides are approximately additive. This fixed combination drug may be used as initial therapy or substituted for previously titrated doses of the individual components. When captopril and hydrochlorothiazide are given together it may not be necessary to administer captopril in divided doses to attain blood pressure control at trough (before the next dose). Also, with such a combination, a daily dose of 15 mg of hydrochlorothiazide may be adequate. Treatment may, therefore, be initiated with captopril and hydrochlorothiazide tablets 25 mg/15 mg once daily. Subsequent titration should be with additional doses of the components (captopril, hydrochlorothiazide) as single agents or as captopril and hydrochlorothiazide tablets 50 mg/15 mg, 25 mg/25 mg, or 50 mg/25 mg (see DOSAGE AND ADMINISTRATION ). In using captopril and hydrochlorothiazide, consideration should be given to the risk of neutropenia/agranulocytosis (see WARNINGS ). Captopril and hydrochlorothiazide may be used for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, particularly those with collagen vascular disease, captopril and hydrochlorothiazide should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to other drug combinations. ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema ).

Dosage and Administration

DOSAGE & ADMINISTRATION DOSAGE MUST BE INDIVIDUALIZED ACCORDING TO PATIENT'S RESPONSE. Captopril and hydrochlorothiazide tablets may be substituted for the previously titrated individual components. Alternatively, therapy may be instituted with a single tablet of captopril and hydrochlorothiazide 25 mg/15 mg taken once daily. For patients insufficiently responsive to the initial dose, additional captopril or hydrochlorothiazide may be added as individual components or by using captopril and hydrochlorothiazide tablets 50 mg/15 mg, 25 mg/25 mg or 50 mg/25 mg, or divided doses may be used. Because the full effect of a given dose may not be attained for 6 to 8 weeks, dosage adjustments should generally be made at 6 week intervals, unless the clinical situation demands more rapid adjustment. In general, daily doses of captopril should not exceed 150 mg and of hydrochlorothiazide should not exceed 50 mg. Captopril and hydrochlorothiazide tablets should be taken one hour before meals. Dosage Adjustment in Renal Impairment: Because captopril and hydrochlorothiazide are excreted primarily by the kidneys, excretion rates are reduced in patients with impaired renal function. These patients will take longer to reach steady-state captopril levels and will reach higher steady-state levels for a given daily dose than patients with normal renal function. Therefore, these patients may respond to smaller or less frequent doses of captopril and hydrochlorothiazide. After the desired therapeutic effect has been achieved, the dose intervals should be increased or the total daily dose reduced until the minimal effective dose is achieved. When concomitant diuretic therapy is required in patients with severe renal impairment, a loop diuretic (e.g., furosemide), rather than a thiazide diuretic is preferred for use with captopril; therefore, for patients with severe renal dysfunction the captopril-hydrochlorothiazide combination tablet is not usually recommended. (See WARNINGS: Captopril: Anaphylactoid Reactions During Membrane Exposure and PRECAUTIONS: Hemodialysis ).

Side Effects (Adverse Reactions)

ADVERSE REACTIONS Captopril : Reported incidences are based on clinical trials involving approximately 7000 patients. Renal : About one of 100 patients developed proteinuria (see WARNINGS ). Each of the following has been reported in approximately 1 to 2 of 1000 patients and are of uncertain relationship to drug use: renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria, and urinary frequency. Hematologic : Neutropenia/agranulocytosis has occurred (see WARNINGS ). Cases of anemia, thrombocytopenia, and pancytopenia have been reported. Dermatologic : Rash, often with pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 4 to 7 (depending on renal status and dose) of 100 patients, usually during the first four weeks of therapy. It is usually maculopapular, and rarely urticarial. The rash is usually mild and disappears within a few days of dosage reduction, short-term treatment with an antihistaminic agent, and/or discontinuing therapy; remission may occur even if captopril is continued. Pruritus, without rash, occurs in about 2 of 100 patients. Between 7 and 10 percent of patients with skin rash have shown eosinophilia and/or positive ANA titers. A reversible associated pemphigoid-like lesion, and photosensitivity, have also been reported. Flushing or pallor has been reported in 2 to 5 of 1000 patients. Cardiovascular : Hypotension may occur; see WARNINGS and PRECAUTIONS (Drug Interactions) for discussion of hypotension with captopril therapy. Tachycardia, chest pain, and palpitations have each been observed in approximately 1 of 100 patients. Angina pectoris, myocardial infarction, Raynaud’s syndrome, and congestive heart failure have each occurred in 2 to 3 of 1000 patients. Dysgeusia : Approximately 2 to 4 (depending on renal status and dose) of 100 patients developed a diminution or loss of taste perception. Taste impairment is reversible and usually self-limited (2 to 3 months) even with continued drug administration. Weight loss may be associated with the loss of taste. Angioedema : Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported in approximately one in 1000 patients. Angioedema involving the upper airways has caused fatal airway obstruction. (See WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema and PRECAUTIONS: Information for Patients ). Cough : Cough has been reported in 0.5 to 2% of patients treated with captopril in clinical trials (see PRECAUTIONS: General: Captopril: Cough ). The following have been reported in about 0.5 to 2 percent of patients but did not appear at increased frequency compared to placebo or other treatments used in controlled trials: gastric irritation, abdominal pain, nausea, vomiting, diarrhea, anorexia, constipation, aphthous ulcers, peptic ulcer, dizziness, headache, malaise, fatigue, insomnia, dry mouth, dyspnea, alopecia, paresthesias. Other clinical adverse effects reported since the drug was marketed are listed below by body system. In this setting, an incidence or causal relationship cannot be accurately determined. Body as a Whole : Anaphylactoid reactions (see WARNINGS: Captopril: Anaphylactoid and Possibly Related Reactions and PRECAUTIONS: Hemodialysis ). General : asthenia, gynecomastia. Cardiovascular : cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope. Dermatologic : bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis. Gastrointestinal : pancreatitis, glossitis, dyspepsia. Hematologic : anemia, including aplastic and hemolytic. Hepatobiliary : jaundice, hepatitis, including rare cases of necrosis, cholestasis. Metabolic : symptomatic hyponatremia. Musculoskeletal : myalgia, myasthenia. Nervous/Psychiatric : ataxia, confusion, depression, nervousness, somnolence. Respiratory : bronchospasm, eosinophilic pneumonitis, rhinitis. Special Senses...

Drug Interactions

Drug Interactions: Captopril : Hypotension—Patients On Diuretic Therapy : Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restrictions or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of captopril. The possibility of hypotensive effects with captopril can be minimized by either discontinuing the diuretic or increasing the salt intake approximately one week prior to initiation of treatment with captopril or initiating therapy with small doses (6.25 or 12.5 mg). Alternatively, provide medical supervision for at least one hour after the initial dose. If hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of normal saline. This transient hypotensive response is not a contraindication to further doses which can be given without difficulty once the blood pressure has increased after volume expansion. Agents Having Vasodilator Activity : Data on the effect of concomitant use of other vasodilators in patients receiving captopril for heart failure are not available; therefore, nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril. If resumed during captopril therapy, such agents should be administered cautiously, and perhaps at lower dosage. Agents Causing Renin Release : Captopril’s effect will be augmented by antihypertensive agents that cause renin release. For example, diuretics (e.g., thiazides) may activate the renin-angiotensin-aldosterone system. Agents Affecting Sympathetic Activity : The sympathetic nervous system may be especially important in supporting blood pressure in patients receiving captopril alone or with diuretics. Therefore, agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive. Agents Increasing Serum Potassium : Since captopril decreases aldosterone production, elevation of serum potassium may occur. Potassium-sparing diuretics such as spironolactone, triamterene, or amiloride, or potassium supplements, should be given only for documented hypokalemia, and then with caution, since they may lead to a significant increase of serum potassium. Salt substitutes containing potassium should also be used with caution. Gold : Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including captopril and hydrochlorothiazide tablets. Inhibitors of Endogenous Prostaglandin Synthesis : It has been...

Contraindications

CONTRAINDICATIONS Captopril : This product is contraindicated in patients who are hypersensitive to captopril or any other angiotensin-converting enzyme inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor). Hydrochlorothiazide : Hydrochlorothiazide is contraindicated in anuria. It is also contraindicated in patients who have previously demonstrated hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs.

Pregnancy and Breastfeeding

Pregnancy Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Nursing Mothers Both captopril and hydrochlorothiazide are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from both drugs, a decision should be made whether to discontinue nursing or to discontinue therapy taking into account the importance of captopril and hydrochlorothiazide to the mother. (See PRECAUTIONS: Pediatric Use. )

Overdosage

OVERDOSAGE Captopril : Correction of hypotension would be of primary concern. Volume expansion with an intravenous infusion of normal saline is the treatment of choice for restoration of blood pressure. While captopril may be removed from the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the circulation of neonates or children. Peritoneal dialysis is not effective for removing captopril; there is no information concerning exchange transfusion for removing captopril from the general circulation. Hydrochlorothiazide : In addition to the expected diuresis, overdosage of thiazides may produce varying degrees of lethargy which may progress to coma within a few hours, with minimal depression of respiration and cardiovascular function and without evidence of serum electrolyte changes or dehydration. The mechanism of thiazide-induced CNS depression is unknown. Gastrointestinal irritation and hypermotility may occur. Transitory increase in BUN has been reported, and serum electrolyte changes may occur, especially in patients with impaired renal function. In addition to gastric lavage and supportive therapy for stupor or coma, symptomatic treatment of gastrointestinal effects may be needed. The degree to which hydrochlorothiazide is removed by hemodialysis has not been clearly established. Measures as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function should be instituted.

How Supplied

HOW SUPPLIED Captopril and Hydrochlorothiazide Tablets, USP are available containing 25 mg or 50 mg of captopril, USP with 15 mg or 25 mg of hydrochlorothiazide, USP providing the following available combinations: 25 mg/15 mg, 25 mg/25 mg, 50 mg/15 mg or 50 mg/25 mg. The 25 mg/15 mg tablets are supplied as a white, round, biconvex tablet debossed with ‘R over 27’ on one side of the tablet and quadrisect scored on the other side. They are available as follows: Bottles of 90 tablets - NDC 16571-827-09 The 25 mg/25 mg tablets are supplied as a peach, round, biconvex tablet debossed with ‘R over 28’ on one side of the tablet and quadrisect scored on the other side. They are available as follows: Bottles of 90 tablets - NDC 16571-828-09 The 50 mg/15 mg tablets are supplied as a white, capsule-shaped, biconvex tablet debossed with ‘ R ’ to the left of the partial score and ‘ 29 ’ to the right of the partial score on one side of the tablet and partially scored on the other side. They are available as follows: Bottles of 90 tablets - NDC 16571-829-09 The 50 mg/25 mg tablets are supplied as a peach, capsule-shaped, biconvex tablet debossed with R to the left of the partial score and 30 to the right of the partial score on one side of the tablet and partially scored on the other side. They are available as follows: Bottles of 90 tablets - NDC 16571-830-09 Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture. Manufactured for: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Issued: 12/2022 200640 PIR83001-00