Candesartan Cilexetil (5 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ATACAND
- ATACAND HCT
- CANDESARTAN CILEXETIL
- CANDESARTAN CILEXETIL AND HYDROCHLOROTHIAZIDE
- CANDESARTAN CILEXETIL; HYDROCHLOROTHIAZIDE
Boxed Warning
• When pregnancy is detected, discontinue candesartan cilexetil and hydrochlorothiazide tablets 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
Indications and Usage
Candesartan cilexitil 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 cilexitil 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 r
Dosage and Administration
The usual recommended starting dose of candesartan cilexetil is 16 mg once daily when it is used as monotherapy in patients who are not volume depleted. Candesartan cilexetil can be administered once or twice daily with total daily doses ranging from 8 mg to 32 mg. Patients requiring further reduction in blood pressure should be titrated to 32 mg. Doses larger than 32 mg do not appear to have a greater blood pressure lowering effect. Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily. Use in Renal Impairment: Dosing recommendations for candesartan cilexetil and hydrochlorothiazide in patients with creatinine clearance < 30 mg/min cannot be provided (see SPECIAL POPULATIONS, Renal Insufficiency). Use in moderate to severe Hepatic Impairment: Candesartan cilexetil and hydrochlorothiazide is not recommended for initiation because the appropriate starting dose, 8 mg, cannot be given. (see SPECIAL POPULATIONS, Hepatic Insufficiency). Replacement Therapy: The combination may be substituted for the titrated components. Dose Titration by Clinical Effect: A patient whose blood pressure is not controlled on 25 mg of hydrochlorothiazide once daily can expect an incremental effect from candesartan cilexetil and hydrochlorothiazide tablets 16 mg/12.5 mg. A patient whose blood pressure is controlled on 25 mg of hydrochlorothiazide but is experiencing decreases in serum potassium can expect the same or incremental blood pressure effects from candesartan cilexetil and hydrochlorothiazide tablets 16 mg/12.5 mg and serum potassium may improve. A patient whose blood pressure is not controlled on 32 mg of candesartan cilexetil can expect incremental blood pressure effects from candesartan cilexetil and hydrochlorothiazide tablets 32 mg/12.5 mg and then 32 mg/25 mg. The maximal antihypertensive effect of any dose of candesartan cilexetil and hydrochlorothiazide tablets can be expected within 4 weeks of initiating that dose. Candesartan cilexetil and hydrochlorothiazid
Contraindications
Candesartan cilexetil and hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to candesartan, to hydrochlorothiazide or to other sulfonamide-derived drugs. Do not co-administer aliskiren with candesartan cliexetil and hydrochlorothiazide in patients with diabetes (see PRECAUTIONS, Drug Interactions). Candesartan cliexetil and hydrochlorothiazide is contraindicated in patients with anuria.
Adverse Reactions
Candesartan Cilexetil-Hydrochlorothiazide Candesartan cilexitil and hydrochlorothiazide tablets has been evaluated for safety in more than 2800 patients treated for hypertension. More than 750 of these patients were studied for at least six months and more than 500 patients were treated for at least one year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse events reported with candesartan cilexitil and hydrochlorothiazide tablets was comparable to placebo. The overall frequency of adverse experiences was not related to dose, age, gender, or race. In placebo-controlled trials that included 1089 patients treated with various combinations of candesartan cilexetil (doses of 2 to 32 mg) and hydrochlorothiazide (doses of 6.25 mg to 25 mg) and 592 patients treated with placebo, adverse events, whether or not attributed to treatment, occurring in greater than 2% of patients treated with candesartan cilexitil and hydrochlorothiazide tablets and that were more frequent for candesartan cilexitil and hydrochlorothiazide tablets than placebo were: Respiratory System Disorder: upper respiratory tract infection (3.6% vs 3.0%); Body as a Whole: back pain (3.3% vs 2.4%); influenza-like symptoms (2.5% vs 1.9%); Central/Peripheral Nervous System: dizziness (2.9% vs 1.2%). Post-Marketing Experience The following have been very rarely reported in post-marketing experience with candesartan cilexetil: Digestive: Abnormal hepatic function and hepatitis. Hematologic: Neutropenia, leukopenia, and agranulocytosis. Immunologic: Angioedema Metabolic and Nutritional Disorders: Hyperkalemia, hyponatremia. Respiratory System Disorders: Cough Skin and Appendages Disorders: Pruritus, rash and urticaria. Rare reports of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers. Hydrochlorothiazide Other adverse experiences that have been reported with hy
Drug Interactions
Because candesartan is not significantly metabolized by the cytochrome P450 system and at therapeutic concentrations has no effects on P450 enzymes, interactions with drugs that inhibit or are metabolized by those enzymes would not be expected. Interactions common to both Candesartan Cilexetil and Hydrochlorothiazide Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including candesartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving candesartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including candesartan may be attenuated by NSAIDs including selective COX-2 inhibitors. Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Monitor serum lithium levels during concomitant use. Interactions with Candesartan Cilexetil Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on candesartan cilexetil and hydrochlorothiazide and other agents that affect the RAS. Co-administration of candesartan cilexetil and hydrochlorothiazide with potassium sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that raise serum potassium
Overdosage
Candesartan Cilexetil – Hydrochlorothiazide No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg. Limited data are available in regard to overdosage with candesartan cilexetil in humans. The most likely manifestations of overdosage with candesartan cilexetil would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be initiated. For hydrochlorothiazide, the most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. Candesartan cannot be removed by hemodialysis. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. Treatment To obtain up-to-date information about the treatment of overdose, consult your Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and altered pharmacokinetics in your patient.