Kapvay Information
Kapvay (Clonidine) . Indications And Usage
Kapvay (Clonidine) (clonidine hydrochloride) extended-release is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to stimulant medications.
The efficacy of Kapvay (Clonidine) in the treatment of ADHD is based on two controlled trials (one monotherapy and one adjunctive to stimulant medication) in children and adolescents ages 6-17 who met DSM-IV criteria for ADHD hyperactive or combined hyperactive/inattentive subtypes [see ]. In the adjunctive study, Kapvay (Clonidine) was administered to patients who had been on a stable regimen of either methylphenidate or amphetamine (or their derivatives) and who had not achieved an optimal response. The effectiveness of Kapvay (Clonidine) for longer-term use (more than 5 weeks) has not been systematically evaluated in controlled trials.
A diagnosis of ADHD implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; "on the go"; excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.
Kapvay (Clonidine) . Dosage And Administration
Kapvay (Clonidine) is an extended-release tablet formulation of clonidine hydrochloride. While it is dosed twice a day, the same as the immediate-release clonidine formulation, it is not to be used interchangeably with the immediate-release formulation.
Kapvay (Clonidine) is an extended-release tablet and, therefore, must be swallowed whole and never crushed, cut or chewed. Kapvay (Clonidine) may be taken with or without food.
Due to the lack of controlled clinical trial data and differing pharmacokinetic profiles, substitution of Kapvay (Clonidine) for other clonidine products on a mg-per-mg basis is not recommended.
The dose of Kapvay (Clonidine) , 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).
Doses of Kapvay (Clonidine) 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 (Clonidine) is being added-on to a psychostimulant, the dose of the psychostimulant can be adjusted depending on the patient's response to Kapvay (Clonidine) .
Kapvay (Clonidine) . Dosage Form And Strengths
Kapvay (Clonidine) tablets are available in two strengths, 0.1 mg and 0.2 mg as an extended-release formulation. Both the 0.1 mg and 0.2 mg tablets are white, non-scored, standard convex with debossing on one side. The 0.1 mg tablets are round and the 0.2 mg tablets are oval. Kapvay (Clonidine) tablets must be swallowed whole and never crushed, cut or chewed.
Kapvay (Clonidine) . Contraindications
Kapvay (Clonidine) should not be used in patients with known hypersensitivity to clonidine.
Kapvay (Clonidine) . Warnings And Precautions
Treatment with Kapvay (Clonidine) can cause dose related decreases in blood pressure and heart rate. In patients that completed 5 weeks of treatment in a controlled, fixed-dose monotherapy study in pediatric patients, during the treatment period the maximum placebo-subtracted mean change in systolic blood pressure was -4.0 mmHg on Kapvay (Clonidine) 0.2 mg/day and -8.8 mmHg on Kapvay (Clonidine) 0.4 mg/day. The maximum placebo-subtracted mean change in diastolic blood pressure was -4.0 mmHg on Kapvay (Clonidine) 0.2 mg/day and -7.3 mmHg on Kapvay (Clonidine) 0.4 mg/day. The maximum placebo-subtracted mean change in heart rate was -4.0 beats per minute on Kapvay (Clonidine) 0.2 mg/day and -7.7 beats per minute on Kapvay (Clonidine) 0.4 mg/day.
During the taper period of the fixed-dose monotherapy study the maximum placebo-subtracted mean change in systolic blood pressure was +3.4 mmHg on Kapvay (Clonidine) 0.2 mg/day and -5.6 mmHg on Kapvay (Clonidine) 0.4 mg/day. The maximum placebo-subtracted mean change in diastolic blood pressure was +3.3 mmHg on Kapvay (Clonidine) 0.2 mg/day and -5.4 mmHg on Kapvay (Clonidine) 0.4 mg/day. The maximum placebo-subtracted mean change in heart rate was -0.6 beats per minute on Kapvay (Clonidine) 0.2 mg/day and -3.0 beats per minute on Kapvay (Clonidine) 0.4 mg/day.
Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Use Kapvay (Clonidine) with caution in patients with a history of hypotension, heart block, bradycardia, or cardiovascular disease, because it can decrease blood pressure and heart rate. Use caution in treating 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. Use Kapvay (Clonidine) with caution in patients treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope. Advise patients to avoid becoming dehydrated or overheated.
No studies evaluating abrupt discontinuation of Kapvay (Clonidine) in children with ADHD have been conducted. In children and adolescents with ADHD, physicians should gradually reduce the dose of Kapvay (Clonidine) in decrements of no more than 0.1 mg every 3 to 7 days. Patients should be instructed not to discontinue Kapvay (Clonidine) therapy without consulting their physician due to the potential risk of withdrawal effects.
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.
In patients who have developed localized contact sensitization to clonidine transdermal system, continuation of clonidine transdermal system or 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 clonidine transdermal system, substitution of oral clonidine hydrochloride may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema).
Kapvay (Clonidine) . Drug Interactions
No drug interaction studies have been conducted with Kapvay (Clonidine) in children. The following have been reported with other oral immediate release formulations of clonidine.
Kapvay (Clonidine) . Use In Specific Populations
A study was conducted in which young rats were treated orally with clonidine hydrochloride from day 21 of age to adulthood at doses of up to 300 mcg/kg/day, which is approximately 3 times the maximum recommended human dose (MRHD) of 0.4 mg/day on a mg/m basis. A slight delay in onset of preputial separation was seen in males treated with the highest dose (with a no-effect dose of 100 mcg/kg/day, which is approximately equal to the MRHD), but there were no drug effects on fertility or on other measures of sexual or neurobehavioral development.
Kapvay (Clonidine) has not been studied in children with ADHD less than 6 years old.
Kapvay (Clonidine) . Overdosage
Clonidine overdose:
Consult with a Certified Poison Control Center for up-to-date guidance and advice.
Kapvay (Clonidine) . Description
Kapvay (Clonidine) (clonidine hydrochloride) extended-release is a centrally acting alpha-adrenergic agonist available as 0.1 mg or 0.2 mg extended-release tablets for oral administration. Each 0.1 mg and 0.2 mg tablet is equivalent to 0.087 mg and 0.174 mg, respectively, of the free base.
The inactive ingredients are sodium lauryl sulfate, lactose monohydrate, hypromellose type 2208, partially pregelatinized starch, colloidal silicon dioxide, and magnesium stearate. The formulation is designed to delay the absorption of active drug in order to decrease peak to trough plasma concentration differences. Clonidine hydrochloride is an imidazoline derivative and exists as a mesomeric compound. The chemical name is 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride. The following is the structural formula:
CHClN•HCl Mol. Wt. 266.56
Clonidine hydrochloride is an odorless, bitter, white, crystalline substance soluble in water and alcohol.
Kapvay (Clonidine) Nonclinical Toxicology
Clonidine HCl was not carcinogenic when administered in the diet of rats (for up to 132 weeks) or mice (for up to 78 weeks) at doses of up to 1620 (male rats), 2040 (female rats), or 2500 (mice) mcg/kg/day. These doses are approximately 20, 25, and 15 times, respectively, the maximum recommended human dose (MRHD) of 0.4 mg/day on a mg/m basis.
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 HCl doses as high as 150 mcg/kg/day (approximately 3 times the MRDHD on a mg/m basis). In a separate experiment, fertility of female rats appeared to be adversely affected at dose levels of 500 and 2000 mcg/kg/day (10 and 40 times the MRHD on a mg/ m basis).
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 adult patients before, and periodically after, the start of clonidine therapy for hypertension. 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.
Kapvay (Clonidine) . Clinical Studies
The efficacy of Kapvay (Clonidine) in the treatment of ADHD was established in 2 (one monotherapy and one adjunctive therapy) placebo-controlled trials in pediatric patients aged 6 to 17, who met DSM-IV criteria of ADHD hyperactive or combined hyperactive/inattentive subtypes. Signs and symptoms of ADHD were evaluated using the investigator administered and scored ADHD Rating Scale-IV-Parent Version (ADHDRS-IV) total score including hyperactive/impulsivity and inattentive subscales.
Study 1 was an 8-week randomized, double-blind, placebo-controlled, fixed dose study of children and adolescents aged 6 to 17 (N=236) with a 5-week primary efficacy endpoint. Patients were randomly assigned to one of the following three treatment groups: Kapvay (Clonidine) (CLON) 0.2 mg/day (N=78), Kapvay (Clonidine) 0.4 mg/day (N=80), or placebo (N=78). Dosing for the Kapvay (Clonidine) groups started at 0.1 mg/day and was titrated in increments of 0.1 mg/week to their respective dose (as divided doses). Patients were maintained at their dose for a minimum of 2 weeks before being gradually tapered down to 0.1 mg/day at the last week of treatment. At both doses, improvements in ADHD symptoms were statistically significantly superior in Kapvay (Clonidine) -treated patients compared with placebo-treated patients at the end of 5 weeks as measured by the ADHDRS-IV total score.
Study 2 was an 8-week randomized, double-blind, placebo-controlled, flexible dose study in children and adolescents aged 6 to 17 (N=198) with a 5-week primary efficacy end point. Patients had been treated with a psychostimulant (methylphenidate or amphetamine) for four weeks with inadequate response. Patients were randomly assigned to one of two treatment groups: Kapvay (Clonidine) adjunct to a psychostimulant (N=102) or psychostimulant alone (N=96). The Kapvay (Clonidine) dose was initiated at 0.1 mg/day and doses were titrated in increments of 0.1 mg/week up to 0.4 mg/day, as divided doses, over a 3-week period based on tolerability and clinical response. The dose was maintained for a minimum of 2 weeks before being gradually tapered to 0.1 mg/day at the last week of treatment. ADHD symptoms were statistically significantly improved in Kapvay (Clonidine) plus stimulant group compared with the stimulant alone group at the end of 5 weeks as measured by the ADHDRS-IV total score.
Kapvay (Clonidine) How Supplied/storage And Handling
Kapvay (Clonidine) extended-release tablets are white, non-scored, standard convex with debossing ("651" for 0.1 mg and "652" for 0.2 mg) on one side.
The 0.1 mg are round tablets supplied in bottles containing 60 (NDC 59630-658-60) or 180 tablets (NDC 59630-658-18).
The 0.2 mg are oval tablets supplied in bottles containing 60 (NDC 59630-659-60) or 180 tablets (NDC 59630-659-18).
Kapvay (Clonidine) Patient Counseling Information
Kapvay (Clonidine)
Kapvay (Clonidine)
Kapvay (Clonidine) . Mg tablet Bottle Label
NDC 59630-658-60
Kapvay (Clonidine)
(clonidine hydrochloride) extended-release tablets 0.1 mg 60 count bottle label
0.1 mg
Rx Only
Shionogi Pharma, Inc.
Kapvay (Clonidine) . Mg tablet Bottle Label
NDC 59630-659-60
Kapvay (Clonidine)
(clonidine hydrochloride) extended-release tablets 60 count bottle label
0.2 mg
Rx Only
Shionogi Pharma, Inc.
