Sedapen

Approved Indications:

• Anxiety disorders and short-term relief of symptoms of anxiety.
• Muscle spasms due to musculoskeletal conditions or neurological disorders.
• Seizure disorders, including adjunctive therapy for status epilepticus.
• Alcohol withdrawal syndrome, including acute agitation.
• Sedation before medical procedures or surgery.
• Management of acute agitation or delirium.
• Treatment of benzodiazepine withdrawal symptoms (clinically accepted in some cases).

Off-label / Clinically Accepted Uses:

• Management of insomnia related to anxiety or transient situational stress.
• Adjunctive treatment in spasticity related to cerebral palsy, multiple sclerosis.
• Use in refractory epilepsy for seizure clusters or emergency control.
• Treatment of catatonia in psychiatric settings.
• Control of severe agitation in psychiatric or critical care settings.

Route: Oral, Intramuscular (IM), Intravenous (IV), Rectal.

Adult Dosage:

• Anxiety: 2–10 mg orally, 2 to 4 times daily, adjusted per response.
• Muscle Spasm: 2–10 mg orally, 3 to 4 times daily.
• Seizures:
• IV/IM: 5–10 mg every 10 to 15 minutes as needed, max 30 mg/day.
• Rectal gel (for acute seizures): 0.2 to 0.5 mg/kg; maximum single dose depends on formulation.
• Alcohol withdrawal: 10 mg orally 3 to 4 times daily initially, tapered over days.
• Sedation: 5–15 mg IV/IM prior to procedure.

Pediatric Dosage:

• Seizures: 0.1 to 0.3 mg/kg IV/IM every 2 to 4 hours as needed, max 10 mg/dose.
• Use cautiously, doses adjusted by weight and clinical response.

Elderly:

• Start with lower doses (2–2.5 mg once or twice daily) due to increased sensitivity and risk of sedation, falls, and cognitive impairment.

Special Populations:

• Hepatic impairment: Reduce dose and frequency; increased half-life due to impaired metabolism.
• Renal impairment: No significant dose adjustment needed, but monitor clinical response.

Administration Notes:

• IV administration should be slow to avoid hypotension or respiratory depression.
• Rectal gel used for seizure emergencies should be administered as per approved protocol.
• Avoid abrupt discontinuation after long-term use to prevent withdrawal symptoms.

Diazepam is a benzodiazepine that acts by potentiating the effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system. It binds to specific benzodiazepine sites on the GABA-A receptor complex, increasing the frequency of chloride channel opening. This hyperpolarizes neurons, reducing neuronal excitability and producing anxiolytic, sedative-hypnotic, muscle relaxant, anticonvulsant, and amnestic effects. The overall outcome is CNS depression leading to relief from anxiety, muscle relaxation, and seizure control.

• Absorption: Rapid and nearly complete after oral administration; peak plasma levels in 1–1.5 hours.
• Distribution: Widely distributed with high lipid solubility; crosses blood-brain barrier and placenta; protein binding approximately 98%.
• Metabolism: Extensively metabolized in the liver via CYP3A4 and CYP2C19 into active metabolites including desmethyldiazepam (long half-life), temazepam, and oxazepam.
• Elimination: Metabolites excreted mainly in urine.
• Onset: Oral: 30–60 minutes; IV: within minutes.
• Half-life: Parent drug 20–50 hours; active metabolites may extend half-life up to 100 hours, contributing to prolonged effects.

• Pregnancy:
• FDA Category D. Associated with risk of congenital malformations, especially with first-trimester exposure. Potential for neonatal withdrawal or floppy infant syndrome if used late in pregnancy.
• Lactation:
• Excreted in breast milk; may cause sedation and feeding difficulties in the infant. Caution advised; benefits should outweigh risks.
• Note: Use only if clearly needed and under close supervision during pregnancy and breastfeeding.

• Benzodiazepine
• Anxiolytic, Sedative-Hypnotic, Anticonvulsant, Muscle Relaxant

• Known hypersensitivity to diazepam or other benzodiazepines.
• Severe respiratory insufficiency.
• Severe hepatic impairment.
• Myasthenia gravis.
• Sleep apnea syndrome.
• Acute narrow-angle glaucoma.
• Use in neonates (except under specialist guidance).

• Use with caution in elderly or debilitated patients due to increased risk of sedation, falls, and cognitive impairment.
• Risk of dependence, tolerance, and withdrawal syndrome with prolonged use; avoid abrupt discontinuation.
• CNS depressant effects may be potentiated by alcohol, opioids, or other CNS depressants—monitor closely.
• Respiratory depression risk, especially in patients with compromised pulmonary function.
• Paradoxical reactions such as agitation, aggression, or hallucinations can occur, particularly in children and elderly.
• Monitor liver function in long-term therapy.
• Caution in patients with a history of substance abuse or psychiatric disorders.

Common:

• Drowsiness, fatigue, dizziness
• Muscle weakness
• Ataxia, impaired coordination
• Cognitive impairment, confusion (especially elderly)
• Mild hypotension

Serious/Rare:

• Respiratory depression and apnea (especially IV administration)
• Paradoxical reactions (agitation, aggression, hallucinations)
• Dependence, tolerance, withdrawal seizures
• Hepatic dysfunction
• Allergic reactions (rash, angioedema)

• CNS depressants (alcohol, opioids, barbiturates): Increased sedation and respiratory depression.
• CYP3A4 inhibitors (ketoconazole, erythromycin): Increased diazepam plasma levels, prolonged sedation.
• CYP3A4 inducers (rifampin, carbamazepine): Reduced diazepam efficacy.
• Cimetidine: May increase plasma levels.
• Phenytoin: Potential altered metabolism of both drugs.
• Oral contraceptives: May increase diazepam levels.
• Theophylline and aminophylline: May decrease diazepam sedation.

• Current clinical guidelines recommend limiting benzodiazepine use to short-term therapy due to dependence risks.
• Emphasis on careful patient selection, especially in elderly and patients with respiratory disease.
• Increased warnings on combined use with opioids due to risk of fatal respiratory depression.
• Updated recommendations stress gradual tapering to discontinue therapy safely.
• Use in seizure emergencies remains an important indication; rectal gel formulations have been widely adopted for out-of-hospital use.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep container tightly closed.
• Do not freeze.
• Store oral and injectable forms separately and according to manufacturer’s instructions.
• Keep out of reach of children.