# Kapvay ### (clonidine hydrochloride, extended release) **Kapvay** (clonidine hydrochloride extended-release tablets); not controlled
[**Full Prescribing Information**](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0100c70d-7fde-46a1-8374-940550a27e43&type=display)[**DailyMed Drug Information**](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0100c70d-7fde-46a1-8374-940550a27e43)
--- ### **Summary** Kapvay is extended-release clonidine, a central alpha-2 adrenergic agonist and the first clonidine product approved for ADHD, in patients 6 to 17 years, as monotherapy or added to a stimulant. The tablet flattens the peak of immediate-release clonidine and is given twice daily, with the equal or larger share at bedtime. It is the choice when hyperactivity, impulsivity, tics or sleep onset dominate and a stimulant alone is not enough. Not controlled; the brand is no longer marketed, and generic supplies the product. --- ### **Forms & Strengths** - **Tablets, extended release:** 0.1 mg only, unscored - **No 0.2 mg or 0.3 mg extended-release tablet exists.** Those are immediate-release strengths --- ### **Dosing** - **Age:** 6-17 y/o; not established below 6 years - **Onset:** sedation within hours; ADHD benefit over weeks, trial endpoint at 5 weeks - **Duration:** dosed twice daily, about 12 hours apart; half-life about 12.6 hours - **Release Profile:** extended release; peak about 50% of immediate release, about 5 hours later, bioavailability about 89% - **Initial Dose:** 0.1 mg at bedtime for one week - **Titration:** 0.1 mg/day every 7 days, split twice daily with the equal or larger dose at bedtime: - 0.1 mg/day: 0.1 mg bedtime - 0.2 mg/day: 0.1 mg morning, 0.1 mg bedtime - 0.3 mg/day: 0.1 mg morning, 0.2 mg bedtime - 0.4 mg/day: 0.2 mg morning, 0.2 mg bedtime - **Max Dose:** 0.4 mg/day as 0.2 mg twice daily; higher doses were not evaluated - **Considerations:** Swallow whole, since the 0.1 mg tablet is unscored and crushing speeds release, so a 0.2 mg dose is two tablets and 0.4 mg/day is four. Never substitute mg-for-mg for another clonidine product, and never stop abruptly. --- ### **Pharmacology** - **Mechanism:** Central alpha-2 adrenergic agonist; reduces sympathetic outflow from the locus coeruleus and enhances prefrontal noradrenergic signalling. Mechanism in ADHD unknown. - **Delivery / Release:** Peak about 50% of immediate release, about 5 hours later; bioavailability about 89%. Food has no effect. - **Metabolism:** About 50% hepatic, 40% to 60% renal unchanged. Half-life about 12.6 hours in adults, up to 41 hours in severe renal impairment. - **Pediatric exposure:** Weight-normalised clearance is higher than in adults, 23% lower in females, 11% higher with methylphenidate and **44% lower with amphetamine.** - **Class Positioning:** Non-selective and more sedating than guanfacine ([Intuniv](https://wiki.joshnp.com/link/5)), which is alpha-2A selective. [Onyda XR](https://wiki.joshnp.com/link/119) shares the moiety once daily as a suspension; [immediate-release clonidine](https://wiki.joshnp.com/link/35) is not ADHD approved. --- ### **Indications** - **ADHD, as monotherapy** (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6-17 y/o - **ADHD, as adjunctive therapy to stimulants** (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6-17 y/o --- ### **Off-Label Uses** - **Tic disorders and Tourette syndrome** (ICD-10: F95.1, F95.2): most useful with comorbid ADHD; supported by controlled trials for the class. (AACAP 2013) - **Sleep-onset insomnia in ADHD** (ICD-10: G47.00): limited data; somnolence is a labeled adverse effect, not a demonstrated benefit - **Where the evidence does not support use:** - **Children under 6** (ICD-10: F90.x): insufficient (AHRQ 2018) - **Oppositional defiant disorder and aggression** (ICD-10: F91.3): insufficient - **Anxiety and PTSD** (ICD-10: F41.x, F43.1): insufficient --- ### **Contraindications & Warnings** - **Contraindicated:** history of hypersensitivity to clonidine, including generalised rash, urticaria or angioedema - **Use with caution:** - Hypotension, heart block, bradycardia, cardiovascular or cerebrovascular disease, chronic renal failure; titrate slowly - Syncope, orthostatic hypotension, or a tendency to dehydration; avoid dehydration and overheating - Conduction abnormality or concurrent sympatholytics; severe bradycardia needing pacing reported - Concurrent CNS depressants, because of additive sedation - Renal impairment; set the initial dose by degree of impairment. Haemodialysis needs no supplemental dose - Prior sensitisation to the clonidine patch; oral use may cause generalised rash - **Screen before starting:** - Heart rate and blood pressure, supine and standing; the label makes this mandatory - Syncope, palpitations, conduction disease, family history of sudden cardiac death - Renal function - Sedating and sympatholytic co-medication, including beta-blockers and digitalis --- ### **Drug Interactions** - **Sinus node and AV nodal agents** (digitalis, calcium channel blockers, beta-blockers): additive bradycardia and AV block; label says **avoid use.** If unavoidable, check vitals each visit - **CNS depressants** (alcohol, barbiturates, benzodiazepines, phenothiazines, sedating antihistamines): potentiated sedation; the label says **avoid use** - **Antihypertensives:** potentiated hypotension; monitor blood pressure and adjust - **Tricyclic antidepressants:** may counteract the hypotensive effect; monitor blood pressure and adjust - **Amphetamine:** clonidine clearance 44% lower, so exposure is higher than with methylphenidate; titrate more cautiously and watch for sedation and bradycardia --- ### **Administration** - Twice daily, about 12 hours apart, larger or equal share at bedtime; week 1 bedtime only - **Swallow whole.** Do not crush, chew or break; the 0.1 mg tablet is unscored and cannot be halved - A 0.2 mg dose is two 0.1 mg tablets, and 0.4 mg/day is four tablets a day. Write the quantity accordingly - For a child who cannot swallow tablets, [Onyda XR](https://wiki.joshnp.com/link/119) is extended-release clonidine as a suspension - **Missed dose:** skip it; never exceed the prescribed daily total. Food does not matter - **Switching:** no mg-for-mg substitution with [immediate-release clonidine](https://wiki.joshnp.com/link/35), Nexiclon XR or the patch; stop it and titrate from 0.1 mg - Do not stop abruptly; see Discontinuation & Taper --- ### **Side Effects** - **Common** (monotherapy, 0.2 / 0.4 mg/day vs placebo): - Somnolence 38 / 31 vs 4%; fatigue 16 / 13 vs 1%; headache 20 / 13 vs 16% - Upper abdominal pain 15 / 10 vs 12%; irritability 9 / 5 vs 4%; nightmare 4 / 9 vs 0% - As adjunct: somnolence 19 vs 7%, fatigue 14 vs 4% - Stopped for adverse effects: 7% at 0.2 mg/day, 20% at 0.4 mg/day, vs 1% placebo - **Serious:** - Rebound hypertension on abrupt discontinuation; taper - Dose-related hypotension and bradycardia; at 0.4 mg/day systolic fell 8.8, diastolic 7.3 mmHg, heart rate 7.7 bpm - Syncope; stop and check orthostatic vitals before further titration - Conduction abnormality or AV block; severe bradycardia has needed pacing. Obtain an ECG and stop - Allergic reactions including angioedema; discontinue - Hallucinations and QT prolongation, post-marketing; discontinue and reassess --- ### **Monitoring & Labs** - **Heart rate and blood pressure:** baseline, 1 to 2 weeks after each increment, then every 3 months; hold titration for bradycardia by age - **Orthostatics:** lying and standing at baseline, every dose change, and any dizziness visit - **Sedation:** ask about school-day sleepiness at every titration visit and every visit for 3 months - **Rebound hypertension risk:** at every refill confirm no missed doses; recheck blood pressure at each taper step - **ADHD response:** rated scale at 5 to 8 weeks, matching the trial endpoint - **ECG:** not routine; baseline if conduction disease, syncope history or concurrent sympatholytics, and promptly for new syncope or bradycardia - **Renal function:** baseline and annually - **Mood and perception:** ask about hallucinations and mood change each visit - **Laboratory:** no routine laboratory monitoring required --- ### **Discontinuation & Taper** - **Never stop abruptly.** Reduce the total daily dose by no more than 0.1 mg every 3 to 7 days; from 0.4 mg/day that is 12 days to 4 weeks - Abrupt cessation in adults: headache, tachycardia, nausea, flushing, chest tightness, anxiety - With immediate-release clonidine: nervousness, agitation, tremor, and a rapid rise in blood pressure - Even trial tapers caused events: abdominal pain 6% and raised heart rate 3% at 0.4 mg/day - Measure blood pressure and heart rate at each taper step and after the last dose - A vomiting illness that prevents dosing is de facto abrupt discontinuation; tell families to call - **Drug holidays are not appropriate for this class.** Weekend and summer breaks are a rebound hypertension risk here --- ### **Pregnancy & Lactation** - **Pregnancy:** decades of human use show no identified risk of major birth defects or miscarriage. Animal resorptions at 10x (rat) and 5x (mouse); no rabbit effect to 3x. - **Lactation:** relative infant dose 4.1% to 8.4%; milk levels about double maternal serum. Most infants unaffected; one case of sedation, hypotonia and apnoea. Monitor for lethargy, tachypnoea and poor feeding. (LactMed 2024) - **Lactation, milk supply:** dose-related oxytocin and prolactin effects, with postpartum galactorrhea reported. Other agents are preferred while nursing a newborn or preterm infant. (LactMed 2024) - **Fertility:** animal studies suggest impaired fertility in both sexes - **Exposure Registry:** National Pregnancy Registry for ADHD Medications, 1-866-961-2388, [womensmentalhealth.org](https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/) --- ### **Counseling Points** - **Counsel the family on:** - Sleepiness in the first weeks: expected, dose related, commonest reason for stopping - The ADHD benefit taking weeks while sleepiness arrives on night one - The twice-daily schedule, larger dose at bedtime; this is not the once-daily clonidine - Swallowing the tablet whole, and that a 0.2 mg dose is two tablets since there is no half tablet - Never stopping on their own; name rebound high blood pressure in those words, and never doubling a missed dose - Calling if a stomach bug stops the medicine going down - Avoiding alcohol and sedating medicines, including antihistamines - **Advise them to call for:** - Fainting, or dizziness on standing that does not settle - A pulse that feels very slow or irregular - Daytime sleepiness affecting school, or a child hard to wake - Severe headache with blurred vision, especially after missed doses - New hives, facial or lip swelling, a widespread rash, or hallucinations - Any vomiting illness that stops the medicine going down --- ### **References** 1. DailyMed. Clonidine hydrochloride extended-release tablets prescribing information. Actavis Pharma, Inc. 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0100c70d-7fde-46a1-8374-940550a27e43 2. DailyMed. Clonidine hydrochloride extended-release tablets, USP prescribing information. Ajanta Pharma USA Inc. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df80255e-f942-4d9f-8edd-cc95795772cb 3. LactMed. Clonidine. Drugs and Lactation Database, National Institute of Child Health and Human Development. 2024. https://www.ncbi.nlm.nih.gov/books/NBK501628/ 4. American Academy of Pediatrics. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/ 5. AACAP. Practice parameter for the assessment and treatment of children and adolescents with tic disorders. Journal of the American Academy of Child and Adolescent Psychiatry. 2013. https://www.jaacap.org/article/S0890-8567(13)00695-3/fulltext 6. AHRQ. Attention deficit hyperactivity disorder: diagnosis and treatment in children and adolescents. Comparative Effectiveness Review No. 203. 2018. https://www.ncbi.nlm.nih.gov/books/NBK487764/ 7. FDA. openFDA National Drug Code Directory, clonidine, queried by generic name across all labelers. 2026. https://api.fda.gov/drug/ndc.json?search=generic\_name:%22clonidine%22&limit=1000