Clodan
Clodan
Generic Name
Clodan
Mechanism
- Selective positive allosteric modulator of the γ‑aminobutyric acid‑A (GABA‑A) receptor complex, especially the α4βδ subunit.
- Enhances GABA‑induced chloride influx, leading to neuronal hyperpolarization.
- Produces rapid onset sedation with a modest impact on REM suppression, preserving sleep architecture relative to benzodiazepines.
- Rapidly metabolized by hepatic UDP‑glucuronosyltransferase (UGT) isoenzymes, limiting accumulation in renal impairment.
Pharmacokinetics
| Parameter | Clodan (IV) | Clodan (PO) |
| Absorption |
• • Oral bioavailability ~75% • Peak plasma concentration 15‑30 min | |
| Distribution |
• • Plasma protein binding ~60% • CNS penetration (log P = 2.8) | |
| Metabolism |
• Hepatic glucuronidation primarily by UGT1A9 • Minimal CYP involvement | |
| Elimination |
• 90 % excreted in feces (glucuronide conjugates) • Renal clearance <10 % | |
| Half‑life |
• 6.5 h (oral) • 8 h (long‑acting formulation) | |
| Drug‑Drug Interactions |
• Concomitant use with strong CYP3A4 inhibitors may modestly increase exposure; not significant. • No clinically relevant interaction with anticholinergics. |
Indications
- Short‑term treatment of primary insomnia (≤4 weeks).
- Use in patients with difficulty initiating or maintaining sleep.
- Off‑label: anxiety‑related sleep disturbances in patients who cannot tolerate benzodiazepines.
Contraindications
- Contraindicated in patients with:
- Severe hepatic impairment (Child‑Pugh C).
- Known hypersensitivity to clodan or related compounds.
- Severe COPD or chronic respiratory failure; risk of respiratory depression.
- Warnings
- Dependence: Potential for tolerance and withdrawal symptoms; recommend tapering after 2‑4 weeks.
- Elderly: Increased sensitivity; initiate at lower dose.
- Pregnancy/Breastfeeding: Category C; use only if benefits outweigh risks.
Dosing
| Age/Weight/Gender | Initial Dose | Titration | Max Daily Dose |
| Adults (≥18 y) | 5 mg PO at bedtime | Increase by 1–2 mg every 2 days as needed | 10 mg/day |
| Elderly (≥65 y) | 3 mg PO at bedtime | Increase by 1 mg after 3 days | 7 mg/day |
| Pediatric (6‑17 y) | 1 mg/kg PO (max 5 mg) | Increase by 0.5 mg/kg every 5 days | 8 mg/kg/day |
• Titration: Start at the lowest dose and adjust based on efficacy and tolerability.
• Administration: Take with a full glass of water, preferably 30 min before sleep.
Adverse Effects
Common (>10%)
• Drowsiness/tiredness
• Headache
• Dizziness
• Dry mouth
• Mild gastrointestinal upset
Serious (≤1%)
• Respiratory depression (especially with opioids or alcohol)
• Paradoxical agitation or hostility
• Severe hypotension (rare)
• Hepatotoxicity (monitor LFTs in patients with liver disease)
Withdrawal symptoms (if discontinued abruptly):
• Insomnia, anxiety, tremor, malaise, autonomic hyperactivity.
Monitoring
- Baseline: Liver function tests (AST/ALT), CBC, serum electrolytes if comorbid.
- Follow‑up: Repeat LFTs at 2 weeks and 4 weeks.
- Sleep diaries: Frequency of awakenings, sleep latency, total sleep time.
- Cognitive or psychomotor tests the first month in patients >65 y or those using driving.
- Drug interactions: Reassess for new prescriptions that may affect CNS depression.
Clinical Pearls
- Distinct from benzodiazepines: Clodan targets the α4βδ subunit, leading to better preservation of REM sleep and lower abuse liability.
- Taper schedule: Gradually reduce by 1‑2 mg every 3 days; abrupt stop can precipitate rebound insomnia rather than withdrawal seizures.
- Elderly caution: Start at 3 mg and increase no sooner than 7 days—most geriatric patients respond well to 5 mg.
- Combination therapy: Avoid co‑administration with strong CYP3A4 inhibitors or other CNS depressants (e.g., zolpidem, opioids) to mitigate additive sedation.
- Breastfeeding: Minimal excretion in human milk; use only when strictly needed.
- Patient education: Encourage a regular sleep routine and cognitive‑behavioral strategies to maximize effectiveness and reduce dose escalation.
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• *This drug card summarises current evidence and practice guidelines for Clodan. Clinicians should consult local formularies, prescribing information, and the latest literature for any updates or region‑specific regulations.*