Junel 1.5/30
Junel 1.5/30
Generic Name
Junel 1.5/30
Mechanism
- Positive allosteric modulation of GABAA receptors: Clobazam binds to a distinct site on the α‑2/α‑3 subunits, enhancing chloride influx when GABA is present.
- Inhibition of excitatory neurotransmission: The hyperpolarization of neuronal membranes reduces seizure activity and dampens anxiety pathways.
- Selectivity: Lower affinity for α‑1 subunits → reduced risk of sedation and ataxia compared with other benzodiazepines.
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Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | Rapid; Tmax 1–2 h | Oral formulation; food slightly delays absorption. |
| Bioavailability | ~50 % | First‑pass metabolism. |
| Distribution | Large volume (~1,100 L) | High protein binding (~91 % to albumin). |
| Metabolism | Hepatic CYP3A4/2D6 → active metabolites (N‑desmethyl‑clobazam) | N‑desmethyl‑clobazam half‑life ≈ 46 h. |
| Elimination | Renal and biliary | Renal clearance ~0.003 L/h/kg. |
| Half‑life | Induction: 20–35 h; with N‑desmethyl: ~50 h | Prolonged due to active metabolite. |
| Adjustments | Reduce dose in hepatic impairment (moderate) | Shunt liver → ↓ clearance, ↑ exposure. |
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Indications
- Adjunctive therapy for focal seizures (partial‑onset seizures) in adults and children.
- Management of acute benzodiazepine‑resistant seizures when rapid onset is desired.
- Short‑term treatment of agitation or severe anxiety (off‑label, with close monitoring).
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Contraindications
Contraindications
• Known hypersensitivity to clobazam or any benzodiazepine.
• Concomitant use of high‑dose opioid analgesics or other central nervous agents that may increase CNS depression.
Warnings
• Cognitive/psychomotor impairment: Should not drive until effect assessed.
• Re‑emergent diarrhea: Risk after abrupt discontinuation of long‑term therapy.
• Pregnancy Category C: Use only if benefits outweigh risks; monitor fetal development.
• Breastfeeding: Clobazam detectable in breast milk; advise caution.
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Dosing
| Situation | Dose | Route | Frequency | Notes |
| Initial | 5 mg PO BID (total 10 mg/day) | Oral | Twice daily | Start low; titrate up 3–5 mg weekly. |
| Maintenance | 20–35 mg/day (divided) | Oral | Twice daily | Max 35 mg/day. |
| Seizure‑free | 20 mg/day | Oral | Once daily | Maintain until at least 12 weeks. |
| Acute anxiety | 5–10 mg PO every 4–6 h | Oral | PRN | Do not exceed 25 mg/day. |
• Formulation: 1.5 mg tablets – count tablets accordingly (e.g., 3 tablets BID = 9 mg/day).
• With food: Improves tolerance, minimal impact on Tmax.
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Adverse Effects
Common (≥ 5 %)
• Somnolence, dizziness, fatigue.
• Weakness, unsteady gait.
• Headache.
Serious/Uncommon (< 1 %)
• Hypersensitivity rash or Stevens–Johnson syndrome.
• Severe action disorder (paradoxical agitation).
• Delirium or cognitive decline in elderly.
• Tendon rupture (rare).
Withdrawal
• Abrupt cessation can precipitate seizures, anxiety, tremor, or delirium.
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Monitoring
- Baseline: Liver function (AST/ALT), renal function (serum creatinine, eGFR), pregnancy test if applicable.
- Therapeutic Drug Monitoring: Not routinely required unless hepatic impairment or drug interactions suspected.
- Regularly: Physical exam for ataxia, mood changes; seizure diary compliance.
- Annual: Baseline cognitive assessment in elderly patients.
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Clinical Pearls
1. Give “clobazam first‑dose”: A slow titration avoids early withdrawal convulsions seen with abrupt initiation.
2. Active metabolite check: In patients on CYP3A4 inhibitors (ketoconazole, macrolides) serum N‑desmethyl‑clobazam may rise; consider a dose reduction.
3. Biphasic toxicity: Peak CNS depression occurs at 1–2 h, but toxic metabolism may linger until day 3–4 due to the long half‑life of the metabolite.
4. NSAID plus clobazam: NSAIDs can elevate plasma clobazam via CYP inhibition; monitor for increased sedation.
5. Use with caution in fragile elders: The drug’s high protein binding and long half‑life make it prone to accumulation in frail or demented seniors.
6. Avoid benzodiazepine‑dependent patients: Switching to clobazam may precipitate withdrawal; cross‑dose with a short‑acting benzodiazepine if necessary.
7. Dietary fat: Reduces clobazam absorption by ~10 %; advise patients to take separate from high‑fat meals when managing seizures.
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• Key Takeaway:
Junel 1.5/30 (clobazam) is a selective benzodiazepine providing effective adjunctive therapy for focal seizures with a favorable safety profile when titrated appropriately, monitored diligently, and used with caution in vulnerable populations.