Kapvay

(clonidine hydrochloride, extended release)

Kapvay (clonidine hydrochloride extended-release tablets); not controlled

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), which is alpha-2A selective. Onyda XR shares the moiety once daily as a suspension; immediate-release clonidine 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 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, 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

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