A fixed-dose combination (FDC) of a selective serotonin reuptake inhibitor (SSRI) and a benzodiazepine. Paroxetine treats the underlying depressive/anxiety disorder, while Clonazepam provides rapid symptomatic relief of acute anxiety, agitation, and panic. This combination is used for specific, severe presentations but requires careful monitoring due to risks of sedation, dependence, and complex pharmacokinetics.
Adult: One tablet (Paroxetine 12.5mg + Clonazepam 0.5mg) once daily, usually at bedtime. May be initiated at half tablet for first 3-5 days in sensitive patients. Maximum duration of continuous combination therapy should not exceed 4-6 weeks.
Note: Take orally with or without food. Swallow whole with water. Taking at bedtime minimizes daytime sedation. DO NOT crush or chew. Do not discontinue abruptly; taper clonazepam component first under medical guidance.
Paroxetine is a potent and selective inhibitor of neuronal serotonin (5-HT) reuptake in the presynaptic membrane, increasing synaptic 5-HT concentration. Clonazepam is a benzodiazepine that potentiates the effect of the inhibitory neurotransmitter GABA by binding to the GABA-A receptor-chloride channel complex, increasing neuronal membrane permeability to chloride ions, resulting in hyperpolarization and reduced neuronal excitability.
Pregnancy: Category D (Paroxetine): Evidence of human fetal risk (cardiac malformations, particularly atrial/ventricular septal defects, especially in first trimester). Category D (Clonazepam): Potential for neonatal withdrawal syndrome, floppy infant syndrome, and teratogenicity (cleft lip/palate). AVOID in pregnancy unless absolutely necessary. If used, lowest effective dose for shortest duration. Neonatal monitoring required.
Driving: IMPAIRED ABILITY. Causes drowsiness, dizziness, blurred vision, and impaired motor coordination. Patients should not drive or operate heavy machinery, especially during initial treatment and dose adjustments.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Selegiline | Risk of fatal serotonin syndrome. | Contraindicated |
| Other CNS Depressants - Alcohol, Opioids, Barbiturates, Other Benzodiazepines | Profound additive CNS depression, respiratory depression, coma. | Major |
| Strong CYP2D6 Inhibitors (e.g., Quinidine) or Inducers | Alters paroxetine levels. Paroxetine itself is a potent CYP2D6 inhibitor. | Moderate |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin, Fluconazole) | Increases clonazepam levels, increasing sedation. | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin) | Decreases clonazepam levels, reducing efficacy. | Moderate |
| Warfarin, NSAIDs (e.g., Aspirin, Ibuprofen) | Increased risk of bleeding (paroxetine impairs platelet aggregation). | Moderate |
| Tamoxifen | Paroxetine (CYP2D6 inhibitor) reduces conversion to active endoxifen, diminishing efficacy in breast cancer. | Major |
| Digoxin | Paroxetine may increase digoxin levels. | Moderate |
| Theophylline | Clonazepam may antagonize theophylline's effects. | Minor |
Same composition (Paroxetine (12.5mg) + Clonazepam (0.5mg)), different brands: