Catapres-TTS-1

Clinical summary

Indications and usage INDICATIONS AND USAGE Catapres‑TTS ® is indicated in the treatment of hypertension. It may be employed alone or concomitantly with other antihypertensive agents. Dosage and administration DOSAGE AND ADMINISTRATION Apply Catapres‑TTS ® (clonidine transdermal system) once every 7 days to a hairless area of intact skin on the upper outer arm or chest. Each new application of Catapres‑TTS ® should be on a different skin site from the previous location. If the system loosens during 7‑day wearing, the adhesive cover should be applied directly over the system to ensure good adhesion. There have been rare reports of the need for patch changes prior to 7 days to maintain blood pressure control. To initiate therapy, Catapres‑TTS ® dosage should be titrated according to individual therapeutic requirements, starting with Catapres‑TTS ® -1. If after one or two weeks the desired reduction in blood pressure is not achieved, increase the dosage by adding another Catapres‑TTS ® -1 or changing to a larger system. An increase in dosage above two Catapres‑TTS ® -3 is usually not associated with additional efficacy. When substituting Catapres‑TTS ® for oral clonidine or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of Catapres‑TTS ® may not commence until 2‑3 days after initial application. Therefore, gradual reduction of prior drug dosage is advised. Some or all previous antihypertensive treatment may have to be continued, particularly in patients with more severe forms of hypertension. Renal Impairment Patients with renal impairment may benefit from a lower initial dose. Patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis. Warnings and cautions WARNINGS Withdrawal Patients should be instructed not to discontinue therapy without consulting their physician. Sudden cessation of clonidine treatment has, in some cases, resulted in symptoms such as nervousness, agitation, headache, tremor, and confusion accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma. The likelihood of such 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. Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal. When discontinuing therapy with Catapres, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal symptomatology. An excessive rise in blood pressure following discontinuation of Catapres‑TTS ® therapy can be reversed by administration of oral clonidine hydrochloride or by intravenous phentolamine. If therapy is to be discontinued in patients receiving a beta‑blocker and clonidine concurrently, the beta‑blocker should be withdrawn several days before the gradual discontinuation of Catapres‑TTS ® . Drug interactions Drug Interactions Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine is also taking tricyclic antidepressants, the hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose. If a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated. Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction e.g., digitalis, calcium channel blockers, and beta‑blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see Toxicology ). Pregnancy Pregnancy Teratogenic Effects Reproduction studies performed in rabbits at doses up to approximately 3 times the oral maximum recommended daily human dose (MRDHD) of Catapres ® (clonidine hydrochloride) produced no evidence of a teratogenic or embryotoxic potential in rabbits. In rats, however, doses as low as 1/3 the oral MRDHD (1/15 the MRDHD on a mg/m 2 basis) of clonidine 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 oral MRDHD) when the dams were treated on gestation days 6 to 15. Increases in resorption were observed at much higher dose levels (40 times the oral MRDHD on a mg/kg basis; 4 to 8 times the MRDHD on a mg/m 2 basis) in mice and rats treated on