Clarifoam Ef

Clarifoam Ef

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Side Effects & Adverse Reactions

Fetal Toxicity
Teratogenic Effects
Pregnancy Category D

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 candesartan cilexetil and hydrochlorothiazide 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 the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue candesartan cilexetil and hydrochlorothiazide, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to candesartan cilexetil and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia. (See PRECAUTIONS, Pediatric Use.)

There was no evidence of teratogenicity or other adverse effects on embryo-fetal development when pregnant mice, rats or rabbits were treated orally with candesartan cilexetil alone or in combination with hydrochlorothiazide. For mice, the maximum dose of candesartan cilexetil was 1000 mg/kg/day (about 150 times the maximum recommended daily human dose [MRHD]1). For rats, the maximum dose of candesartan cilexetil was 100 mg/kg/day (about 31 times the MRHD1). For rabbits, the maximum dose of candesartan cilexetil was 1 mg/kg/day (a maternally toxic dose that is about half the MRHD1). In each of these studies, hydrochlorothiazide was tested at the same dose level (10 mg/kg/day, about 4, 8, and 15 times the MRHD1 in mouse, rats, and rabbit, respectively). There was no evidence of harm to the rat or mouse fetus or embryo in studies in which hydrochlorothiazide was administered alone to the pregnant rat or mouse at doses of up to 1000 and 3000 mg/kg/day, respectively.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

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1Doses compared on the basis of body surface area. MRHD considered to be 32 mg for candesartan cilexetil and 12.5 mg for hydrochlorothiazide.

Hypotension

Candesartan cilexetil and hydrochlorothiazide can cause symptomatic hypotension. Symptomatic hypotension is most likely to occur in patients who have been volume and/or salt depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Patients with symptomatic hypotension may require temporarily reducing the dose of candesartan cilexetil and hydrochlorothiazide or volume repletion. Volume and/or salt depletion should be corrected before initiating therapy with candesartan cilexetil and hydrochlorothiazide.

In patients with heart failure, candesartan cilexetil and hydrochlorothiazide may cause excessive hypotension, which may lead to oliguria, azotemia, and (rarely) with acute renal failure and death (see WARNINGS: Impaired Renal Function). In such patients, candesartan cilexetil and hydrochlorothiazide therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of candesartan or diuretic is increased.

Impaired Renal Function

Monitor renal function periodically in patients treated with candesartan cilexetil and hydrochlorothiazide. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion) may be at particular risk of developing oliguria, progressive azotemia, or acute renal failure on candesartan cilexetil and hydrochlorothiazide. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on candesartan cilexetil and hydrochlorothiazide.

Potassium Abnormalities

Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesema can result in hypokalemia which appears difficult to treat despite potassium repletion. Monitor serum electrolytes periodically.

In clinical trials of various doses of candesartan cilexetil and hydrochlorothiazide, the incidence of hypertensive patients who developed hypokalemia (serum potassium < 3.5 mEq/L) was 2.5% versus 2.1% for placebo; the incidence of hyperkalemia (serum potassium > 5.7 mEq/L) was 0.4% versus 1% for placebo. No patient receiving candesartan cilexetil and hydrochlorothiazide 16 mg/12.5 mg or 32 mg/12.5 mg was discontinued due to increases or decreases in serum potassium.

Acute Myopia and Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Hypersensitivity Reaction

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.

Legal Issues

There is currently no legal information available for this drug.

FDA Safety Alerts

There are currently no FDA safety alerts available for this drug.

Manufacturer Warnings

There is currently no manufacturer warning information available for this drug.

FDA Labeling Changes

There are currently no FDA labeling changes available for this drug.

Uses

Candesartan cilexetil and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal 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 the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with candesartan cilexetil and hydrochlorothiazide tablets.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

This fixed dose combination is not indicated for initial therapy (see DOSAGE AND ADMINISTRATION).

History

There is currently no drug history available for this drug.

Other Information

Candesartan cilexetil and hydrochlorothiazide tablets combine an angiotensin II receptor (type AT1) antagonist and a diuretic, hydrochlorothiazide.

Candesartan cilexetil, a nonpeptide, is chemically described as (±)2-Ethoxy-1-[[2’-(1H-tetrazol-5-yl)[1,1’-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid-1-[[(Cyclohexyloxy)carbonyl]oxy]ethyl ester.

Its molecular formula is C33H34N6O6, and its structural formula is

Candesartan Structural Formula

Candesartan cilexetil, USP is a white to off-white powder with a molecular weight of 610.66. It is practically insoluble in water, soluble in methylene chloride and slightly soluble in methanol. Candesartan cilexetil is a racemic mixture containing one chiral center at the cyclohexyloxycarbonyloxy ethyl ester group. Following oral administration, candesartan cilexetil undergoes hydrolysis at the ester link to form the active drug, candesartan, which is achiral.

Hydrochlorothiazide is 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-,1,1-dioxide. Its molecular formula is C7H8ClN3O4S2 and its structural formula is

Hydrochlorothiazide Structural Formula

Hydrochlorothiazide, USP is a white, or practically white, practically odorless crystalline powder with a molecular weight of 297.7, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.

Candesartan cilexetil and hydrochlorothiazide tablets are available for oral administration in three tablet strengths of candesartan cilexetil and hydrochlorothiazide.

Candesartan cilexetil and hydrochlorothiazide tablets contain 16 mg or 32 mg of candesartan cilexetil, USP and 12.5 mg or 25 mg of hydrochlorothiazide, USP providing for the following available combinations: 16 mg/12.5 mg, 32 mg/12.5 mg or 32 mg/25 mg. The inactive ingredients of the tablets are carboxymethylcellulose calcium, corn starch, glyceryl stearate, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and yellow iron oxide. The 16 mg/12.5 mg tablet and 32 mg/25 mg tablet also contain red iron oxide as a colorant.

Clarifoam Ef Manufacturers


  • Onset Dermatologics Llc
    Clarifoam Ef (Sulfur,sulfacetamide Sodium) Aerosol, Foam [Onset Dermatologics Llc]

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