KAPVAY — clonidine hydrochloride tablet, extended release
Concordia Pharmaceuticals Inc.
KAPVAY® (clonidine hydrochloride) extended-release is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications [see Clinical Studies (14)].
KAPVAY is an extended-release tablet to be taken orally with or without food. Swallow tablets whole. Do not crush, chew, or break tablets because this will increase the rate of clonidine release.
Due to the lack of controlled clinical trial data and differing pharmacokinetic profiles, substitution of KAPVAY for other clonidine products on a mg-per-mg basis is not recommended [see Clinical Pharmacology (12.3)].
The dose of KAPVAY, administered either as monotherapy or as adjunctive therapy to a psychostimulant, should be individualized according to the therapeutic needs and response of the patient. Dosing should be initiated with one 0.1 mg tablet at bedtime, and the daily dosage should be adjusted in increments of 0.1 mg/day at weekly intervals until the desired response is achieved. Doses should be taken twice a day, with either an equal or higher split dosage being given at bedtime (see Table 1).
|Total Daily Dose||Morning Dose||Bedtime Dose|
|0.1 mg/day||0.1 mg|
|0.2 mg/day||0.1 mg||0.1 mg|
|0.3 mg/day||0.1 mg||0.2 mg|
|0.4 mg/day||0.2 mg||0.2 mg|
Doses of KAPVAY higher than 0.4 mg/day (0.2 mg twice daily) were not evaluated in clinical trials for ADHD and are not recommended.
When KAPVAY is being added-on to a psychostimulant, the dose of the psychostimulant can be adjusted depending on the patient’s response to KAPVAY.
When discontinuing KAPVAY, the total daily dose should be tapered in decrements of no more than 0.1 mg every 3 to 7 days to avoid rebound hypertension [see Warnings and Precautions (5.3)].
If patients miss a dose of KAPVAY, they should skip that dose and take the next dose as scheduled. Do not take more than the prescribed total daily amount of KAPVAY in any 24-hour period.
KAPVAY is available as 0.1 mg strength extended-release tablets. The 0.1 mg tablets are round, white, non-scored, standard convex with debossing on one side. KAPVAY tablets must be swallowed whole and never crushed, cut or chewed.
KAPVAY is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. Reactions have included generalized rash, urticaria, and angioedema [see Adverse Reactions (6)].
Treatment with KAPVAY can cause dose-related decreases in blood pressure and heart rate [see Adverse Reactions (6.1)]. Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Titrate KAPVAY slowly in patients with a history of hypotension, and those with underlying conditions that may be worsened by hypotension and bradycardia; e.g., heart block, bradycardia, cardiovascular disease, vascular disease, cerebrovascular disease, or chronic renal failure. In patients who have a history of syncope or may have a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration, advise patients to avoid becoming dehydrated or overheated. Monitor blood pressure and heart rate, and adjust dosages accordingly in patients treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope.
Somnolence and sedation were commonly reported adverse reactions in clinical studies. In patients that completed 5 weeks of therapy in a controlled, fixed dose pediatric monotherapy study, 31% of patients treated with 0.4 mg/day and 38% treated with 0.2 mg/day versus 4% of placebo treated patients reported somnolence as an adverse event. In patients that completed 5 weeks of therapy in a controlled flexible dose pediatric adjunctive to stimulants study, 19% of patients treated with KAPVAY+stimulant versus 7% treated with placebo+stimulant reported somnolence. Before using KAPVAY with other centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines), consider the potential for additive sedative effects. Caution patients against operating heavy equipment or driving until they know how they respond to treatment with KAPVAY. Advise patients to avoid use with alcohol.
Abrupt discontinuation of KAPVAY can cause rebound hypertension. In adults with hypertension, sudden cessation of clonidine hydrochloride extended-release formulation treatment in the 0.2 to 0.6 mg/day range resulted in reports of headache, tachycardia, nausea, flushing, warm feeling, brief lightheadedness, tightness in chest, and anxiety. In adults with hypertension, sudden cessation of treatment with immediate-release 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.
No studies evaluating abrupt discontinuation of KAPVAY in children with ADHD have been conducted; however, to minimize the risk of rebound hypertension, gradually reduce the dose of KAPVAY in decrements of no more than 0.1 mg every 3 to 7 days. Patients should be instructed not to discontinue KAPVAY therapy without consulting their physician due to the potential risk of withdrawal effects.
In patients who have developed localized contact sensitization to clonidine transdermal system, continuation of clonidine transdermal system or substitution of oral KAPVAY therapy may be associated with the development of a generalized skin rash.
In patients who develop an allergic reaction from clonidine transdermal system, substitution of oral KAPVAY may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema).
The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. There have been post-marketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring IV atropine, IV isoproterenol, and temporary cardiac pacing while taking clonidine. Titrate KAPVAY slowly and monitor vital signs frequently in patients with cardiac conduction abnormalities or patients concomitantly treated with other sympatholytic drugs.
The following serious adverse reactions are described in greater detail elsewhere in labeling:
- Hypotension/bradycardia [see Warnings and Precautions (5.1)]
- Sedation and somnolence [see Warnings and Precautions (5.2)]
- Rebound hypertension [see Warnings and Precautions (5.3)]
- Allergic reactions [see Warnings and Precautions (5.4)]
- Cardiac Conduction Abnormalities [see Warnings and Precautions (5.5)]
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