" Citing a lack of cardiovascular benefit, the FDA is taking the unusual step of withdrawing approvals it had previously given for use of niacin and fenofibric acid with statins to treat high cholesterol.
The decision affects niac"...
Chlorthalidone should be used with caution in severe renal disease. In patients with renal disease, chlorthalidone or related drugs may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function. Chlorthalidone should be used with caution in patients with impaired hepatic function or progressive liver disease, because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Sensitivity reactions may occur in patients with a history of allergy or bronchial asthma.
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported with thiazide diuretics which are structurally related to chlorthalidone. However, systemic lupus erythematosus has not been reported following chlorthalidone administration.
In patients who have developed localized contact sensitization to transdermal clonidine, substitution of oral clonidine hydrochloride therapy may be associated with the development of a generalized skin rash.
In patients who develop an allergic reaction from transdermal clonidine that extends beyond the local patch site (such as generalized skin rash, urticaria, or angioedema), oral clonidine hydrochloride substitution may elicit a similar reaction.
As with all antihypertensive therapy, clonidine hydrochloride should be used with caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease or chronic renal failure.
Patients should be instructed not to discontinue therapy without consulting their physician. Sudden cessation of clonidine treatment has resulted in subjective symptoms such as nervousness, agitation and headache, accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma, but such occurrences have usually been associated with previous administration of high oral doses (exceeding 1.2 mg/day) and/or with continuation of concomitant beta-blocker therapy. Rare instances of hypertensive encephalopathy and death have been reported. When discontinuing therapy with clonidine hydrochloride, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal symptomatology.
An excessive rise in blood pressure following clonidine hydrochloride discontinuance can be reversed by administration of oral clonidine or by intravenous phentolamine. If therapy is to be discontinued in patients receiving beta-blockers and clonidine concurrently, beta-blockers should be discontinued several days before the gradual withdrawal of clonidine hydrochloride.
Administration of clonidine hydrochloride should be continued to within four hours of surgery and resumed as soon as possible thereafter. The blood pressure should be carefully monitored and appropriate measures instituted to control it as necessary.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 132-week (fixed concentration) dietary administration study in rats, clonidine hydrochloride administered at 32 to 46 times the maximum recommended daily human oral dose was unassociated with evidence of carcinogenic potential.
Fertility of male or female rats was unaffected by clonidine hydrochloride doses as high as 150 mcg/kg or about 3 times the maximum recommended daily human oral dose (MRDHD). Fertility of female rats did, however, appear to be affected (in another experiment) at dose levels of 500 to 2000 mcg/kg or 10 to 40 times the MRDHD.
Usage in Pregnancy
Pregnancy Category C
Reproduction studies performed in rabbits at doses up to approximately 3 times the maximum recommended daily human dose (MRDHD) of clonidine hydrochloride have revealed no evidence of teratogenic or embryotoxic potential. In rats however, doses as low as 1/3 the MRDHD were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating. Increased resorptions were not associated with treatment at the same or at higher dose levels (up to 3 times the MRDHD) when dams were treated days 6 to 15 of gestation. Increased resorptions were observed at much higher levels (40 times the MRDHD) in rats and mice treated days 1 to 14 of gestation (lowest dose employed in that study was 500 mcg/kg). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
As clonidine hydrochloride is excreted in human milk, caution should be exercised when it is administered to a nursing woman.
Safety and effectiveness in the pediatric population have not been established.
Hypokalemia and other electrolyte abnormalities, including hyponatremia and hypochloremic alkalosis, are common in patients receiving chlorthalidone. These abnormalities are dose-related but may occur even at the lowest marketed doses of chlorthalidone. Serum electrolytes should be determined before initiating therapy and at periodic intervals during therapy. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. All patients taking chlorthalidone should be observed for clinical signs of electrolyte imbalance, including dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, palpitations and gastrointestinal disturbances, such as nausea and vomiting. Digitalis therapy may exaggerate metabolic effects of hypokalemia especially with reference to myocardial activity.
Any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather: appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In cases of actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone.
Increases in serum glucose may occur and latent diabetes mellitus may become manifest during chlorthalidone therapy (see PRECAUTIONS: Chlorthalidone: DRUG INTERACTIONS). Chlorthalidone and related drugs may decrease serum PBI levels without signs of thyroid disturbance.
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.
All patients receiving chlorthalidone should be observed for clinical signs of fluid or electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No information is available.
Usage in Pregnancy
Pregnancy Category B
Reproduction studies have been performed in the rat and the rabbit at doses up to 420 times the human dose and have revealed no evidence of harm to the fetus due to chlorthalidone. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Thiazides cross the placental barrier and appear in cord blood. The use of chlorthalidone and related drugs in pregnant women requires that the anticipated benefits of the drug be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult.
Thiazides are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from chlorthalidone, 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.
Safety and effectiveness in the pediatric population have not been established.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/28/2009
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