Intuniv
Intuniv
Generic Name
Intuniv
Mechanism
- Selective α2A‑adrenergic agonist: preferentially activates presynaptic α2A receptors, reducing presynaptic norepinephrine release in the prefrontal cortex.
- Enhances prefrontal cortical connectivity → improves working memory, impulse control, and executive function.
- Lowered postsynaptic α2A activity mediates the neurophysiological effect, distinguishing it from non‑selective α2 agonists.
Pharmacokinetics
| Parameter | Value / Description |
| Absorption | Oral, delayed‑release capsules; peak plasma concentration (Tmax) ~6–8 h. |
| Bioavailability | ~8% after single‑dose oral administration (low due to first‑pass). |
| Half‑life | ~17–20 h (extended‑release formulation). |
| Metabolism | Hepatic via CYP2D6 and non‑enzymatic pathways; minimal involvement of CYP3A4/5. |
| Excretion | Primarily renal (~25–30% unchanged), the rest as metabolites. |
| Steady‐state | Achieved after ~2–4 weeks of continuous dosing. |
Indications
- ADHD in patients 6–17 years (FDA‑approved).
- Off‑label therapeutic use in adults with ADHD, agitation, or insomnia associated with ADHD.
- May be combined with stimulants to enhance efficacy and reduce stimulant‑related side effects such as appetite suppression.
Contraindications
| Contraindications | Warnings |
| Hypersensitivity to guanfacine or excipients. | Severe hypotension or postural orthostatic hypotension. |
| Bradycardia (HR < 55 bpm) or third‑degree AV block. | Concomitant use of strong CYP2D6 inhibitors (e.g., fluoxetine) can elevate levels. |
| Significant hepatic dysfunction. | Abrupt discontinuation may cause rebound hypertension; taper slowly. |
| Persistent sleepiness or excessive sedation—discontinue if severe. |
Dosing
1. Initial dose: 1 mg once daily (usually in the evening).
2. Titration: Increase by 0.5–1 mg weekly as tolerated. Max recommended dose: 4 mg/day.
3. Administration: Chew or swallow the capsule whole; do not crush or chew (delayed‑release).
4. Timing: Take at the same time each day to maintain stable levels.
5. Food: Food does not significantly affect absorption; can be taken with or without meals.
*Example titration schedule for a 12‑year‑old:*
| Week | Dose (mg/day) |
| 1–2 | 1 |
| 3–4 | 1.5 |
| 5–6 | 2.5 |
| 7+ | 3.5–4.0 (if needed) |
Adverse Effects
| Category | Examples |
| Common (≥5 %) | Somnolence, fatigue, dry mouth, headache, dizziness, constipation, hypertension, initial hypotension. |
| Moderate (1–5 %) | Bradycardia, decreased appetite, insomnia, insomnia, mild abdominal pain. |
| Serious (<1 %) | Bradyarrhythmias (AV block), severe hypotension, syncope, marked sedation, anaphylaxis (rare). |
• Long‑term effects: Minimal growth suppression reported; monitor height/weight during routine follow‑up.
Monitoring
| Parameter | Frequency |
| Vital signs (BP, HR) | Baseline, 1–2 weeks after dose change, then every 4–6 weeks. |
| Growth metrics (height, weight) | Every visit or as per school health guidelines. |
| Serum creatinine / liver enzymes | Baseline, then annually or if clinically indicated. |
| Sleep quality | Assess daily at titration, especially if somnolence reported. |
| Adverse events | Document at each visit; note any cardiovascular symptoms. |
Clinical Pearls
- Start low, titrate slow: The most common adverse reaction is hypotension; gradual dose escalation mitigates this risk.
- Avoid sudden discontinuation: A rapid dose reduction can trigger rebound hypertension or tachycardia; taper by 0.5 mg per week.
- Adjunct to stimulants: Adding Intuniv can reduce stimulant‑induced insomnia, appetite loss, and peak‑dose jitter.
- Pediatric dosing precision: Use the liquid or chewable formulation for fine‑tuned dosing in younger children (under 6 kg).
- Potential for improved sleep: Many patients note easier sleep onset; consider night‑time dosing for ADHD‑related insomnia.
- Drug interactions: Concomitant use with CYP2D6 inhibitors (fluoxetine, paroxetine) may require closer BP monitoring.
- Non‑cognitive benefits: Emerging evidence suggests Intuniv may slightly improve inhibitory control in children with comorbid oppositional defiant disorder.
--
• Intuniv remains a cornerstone for non‑stimulant ADHD management in pediatric populations, offering a mechanism distinct from stimulants, a favorable side‑effect profile when titrated appropriately, and synergistic benefits when combined with other ADHD therapies.