"The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the marketing of selexipag (Uptravi, Actelion Registration Ltd) for the treatment of adults with pulmonary arterial hypertension (PAH)./"...
Sudden interruption of treatment with oral clonidine has, in some cases, resulted in symptoms such as nervousness, agitation, headache, and tremor accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma. Rare instances of hypertensive encephalopathy, cerebrovascular accidents, and death have been reported after clonidine withdrawal. Sudden cessation of Jenloga (clonidine tablets) treatment in the 0.2 to 0.6 mg per day range resulted in reports of headache, tachycardia, nausea, flushing, warm feeling, brief lightheadedness, tightness in chest, and anxiety, although rebound hypertension as assessed by ambulatory blood pressure monitoring (ABPM) was not noted.
The likelihood of reactions to discontinuation of clonidine therapy appears to be greater after administration of higher doses or continuation of concomitant beta-blocker treatment, and special caution is therefore advised in these situations. An excessive rise in blood pressure following discontinuation of clonidine hydrochloride therapy can be reversed by administration of oral clonidine hydrochloride or by intravenous phentolamine.
When discontinuing therapy with Jenloga (clonidine tablets) , reduce the dose gradually over 2 to 4 days to minimize withdrawal symptomatology. If therapy is to be discontinued in patients receiving a beta-blocker and Jenloga (clonidine tablets) concurrently, withdraw the beta-blocker several days before the gradual discontinuation of Jenloga (clonidine tablets) . Instruct patients not to discontinue therapy without consulting a physician.
In patients who have developed localized contact sensitization to a clonidine transdermal system, substitution of oral clonidine therapy may result in the development of a generalized skin rash.
In patients who develop an allergic reaction from a clonidine transdermal system, substitution of oral clonidine may elicit an allergic reaction (including generalized rash, urticaria, or angioedema).
Use in Patients with Vascular Disease, Cardiac Conduction Disease, or Chronic Renal Failure
Uptitrate slowly in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease or chronic renal failure.
Continue administration of Jenloga (clonidine tablets) to within four hours of surgery and resume as soon as possible thereafter. Carefully monitor blood pressure during surgery. Additional measures to control blood pressure should be readily available if required.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Clonidine HCI was not carcinogenic when administered in the diets of rats (up to 132 weeks of exposure) at doses as high as 1620 mcg/kg/day in males (human equivalent dose: 260 mcg/kg/day) and 2040 mcg/kg/day in females (HED 324 mcg/kg/day) or the diets of mice (up to 78 weeks of exposure) at doses as high as 2500 mcg/kg/day (HED 203 mcg/kg/day). There was no evidence of genotoxicity in the Ames test for mutagenicity or mouse micronucleus test for clastogenicity. Fertility of male or female rats was unaffected by clonidine HCI doses as high as 150 mcg/kg/day (HED 24 mcg/kg/day). In a separate experiment, fertility of female rats appeared to be adversely affected at dose levels of 500 and 2000 mcg/kg/day (HED 80 and 324 mcg/kg/day, respectively).
In several studies with oral clonidine hydrochloride, a dose-dependent increase in the incidence and severity of spontaneous retinal degeneration was seen in albino rats treated for six months or longer. Tissue distribution studies in dogs and monkeys showed a concentration of clonidine in the choroid. In combination with amitriptyline, clonidine hydrochloride administration led to the development of corneal lesions in rats within 5 days.
In view of the retinal degeneration seen in rats, eye examinations were performed during clinical trials in 908 patients before, and periodically after, the start of clonidine therapy. In 353 of these 908 patients, the eye examinations were carried out over periods of 24 months or longer. Except for some dryness of the eyes, no drug-related abnormal ophthalmological findings were recorded and, according to specialized tests such as electroretinography and macular dazzle, retinal function was unchanged.
Use In Specific Populations
Pregnancy Category C
Oral administration of clonidine HCI to pregnant rabbits during embryo/fetal organogenesis, at doses up to 80 mcg/kg/day (human equivalent dose 26 mcg/kg/day), produced no evidence of teratogenic or embryotoxic potential. In pregnant rats, however, doses as low as 15 mcg/kg/day (HED 2.4 mcg/kg/day) were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating and throughout gestation. Increased resorptions were not associated with treatment at the same or higher dose levels (up to 150 mcg/kg/day (HED 24 mcg/kg/day)) when treatment of the dams was restricted to gestation days 6-15. Increases in resorptions were observed in both mice and rats at 500 or more mcg/kg/day (HED 80 mcg/kg/day for rats and 40 mcg/kg/day for mice) when the animals were treated on gestation days 1-14.
Clonidine hydrochloride is excreted in human milk and should generally not be administered to a nursing woman.
Safety and effectiveness in pediatric patients below the age of eighteen have not been established.
Patients with Renal Impairment
The initial dosage should be based on the degree of impairment. Monitor patients carefully for hypotension and bradycardia, and titrate to higher doses cautiously. Because only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/25/2010
Additional Jenloga Information
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