Schedule H

Oral, Sublingual

• Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

• Sublingual tablets: 0.25 mg, 0.5 mg

• Extended-release tablets: 0.5 mg, 1 mg, 2 mg (limited availability)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Generalised Anxiety Disorder (GAD)

Parameter Dose

Starting dose 0.25–0.5 mg orally twice to three times daily

Titration Increase by 0.25–0.5 mg every 3–4 days based on clinical response

Usual maintenance dose 0.5–4 mg/day in divided doses (2–3 times daily)

Maximum dose 4 mg/day

Clinical Notes:

• Use lowest effective dose for shortest possible duration

• Short-acting agent; monitor for breakthrough anxiety between doses

• Taper gradually when discontinuing (reduce by 0.25–0.5 mg every 3 days)

• Not first-line for chronic anxiety — prefer SSRIs for long-term management

• Reassess need for continuation every 2–4 weeks

1. Panic Disorder (With or Without Agoraphobia)

Parameter Dose

Starting dose 0.5 mg orally three times daily (OR 0.5–1 mg/day in divided doses)

Titration Increase by 0.5–1 mg/day every 3–4 days based on response and tolerability

Usual maintenance dose 2–6 mg/day in divided doses

Maximum dose 10 mg/day (specialist psychiatry supervision required)

Clinical Notes:

• Higher doses often required compared to GAD

• Extended-release formulation may improve compliance and reduce interdose rebound

• Doses >6 mg/day require specialist psychiatric evaluation

• Combine with cognitive behavioural therapy for optimal outcomes

• Avoid abrupt discontinuation — high risk of rebound panic and withdrawal seizures

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Pre-procedural / Situational Anxiety (OFF-LABEL) 0.25–0.5 mg once or twice daily 1–3 days only Not required for short-term Indian hospital protocols; pragmatic use

Adjunctive Therapy in Treatment-Resistant Depression with Anxiety Features (OFF-LABEL) 0.25–0.5 mg two to three times daily Short-term only (2–4 weeks maximum) Specialist only (Psychiatrist) Limited evidence; Indian psychiatric practice consensus

Acute Alcohol Withdrawal — Mild to Moderate (OFF-LABEL) 0.5–1 mg three to four times daily 3–7 days with tapering Specialist only Indian de-addiction centre protocols; not first-line (prefer diazepam/lorazepam)

PAEDIATRIC DOSING (Specialist Only)

⚠️ Not routinely recommended in patients under 18 years of age. Use only under specialist paediatric psychiatry supervision.

Primary Indications

Not applicable — no approved paediatric indications in India.

Secondary Indications – Paediatrics (Off-label)

Indication Age Dose Duration Supervision Evidence Basis

Severe Refractory Anxiety Disorder (OFF-LABEL) ≥12 years only 0.005–0.02 mg/kg/day in 2–3 divided doses; titrate cautiously up to 0.06 mg/kg/day Short-term only (maximum 2–4 weeks) Specialist only (Child Psychiatrist) Limited evidence; Indian specialist psychiatric practice

Safety Monitoring:

• Sedation level, paradoxical reactions (agitation, aggression)

• Behavioural changes, cognitive impairment

• Signs of dependence

Age Restriction:

• Avoid below 12 years of age except under exceptional circumstances with specialist child psychiatry supervision

• Not recommended below 6 years under any circumstances

Mild to Moderate Impairment No dose adjustment required

Dialysis Not significantly removed by haemodialysis; no supplemental dose required

• Known hypersensitivity to alprazolam or other benzodiazepines

• Acute narrow-angle glaucoma

• Concurrent use with strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, cobicistat)

• Severe respiratory insufficiency or respiratory depression

• Acute pulmonary insufficiency

• Myasthenia gravis

• Sleep apnoea syndrome (severe/uncontrolled)

• Severe hepatic impairment

• Elderly or debilitated patients (increased sensitivity, fall risk)

• History of substance use disorder or alcohol dependence (high dependence potential)

• Mild to moderate sleep apnoea

• Chronic obstructive pulmonary disease

• Hepatic impairment (mild to moderate)

• History of depression or suicidal ideation

• Concurrent use with other CNS depressants

• Patients requiring prolonged treatment (dependence risk)

• History of paradoxical reactions to benzodiazepines

• Patients operating machinery or driving

Parameter Information

Overall Safety Avoid unless clearly necessary; associated with increased risk of congenital malformations (first trimester) and neonatal complications

Risk Floppy infant syndrome, neonatal withdrawal, respiratory depression if used near term

Preferred Alternatives SSRIs (sertraline, escitalopram) under obstetric-psychiatric supervision for chronic anxiety

When Use May Be Justified Acute, short-term use for severe anxiety when non-pharmacological and SSRI options have failed; joint obstetric-psychiatry decision

Monitoring Fetal growth, neonatal sedation, withdrawal symptoms after birth; avoid doses >2 mg/day near term

Parameter Information

Compatibility Not recommended for chronic use during breastfeeding

Expected Drug Level in Milk Low to moderate

Risk to Infant Sedation, poor feeding, weight loss, withdrawal symptoms with chronic exposure

Preferred Alternatives Sertraline or escitalopram (if antidepressant/anxiolytic needed)

If Short-term Use Essential Avoid breastfeeding for 4–6 hours after each dose; monitor infant closely

Infant Monitoring Sedation, feeding difficulties, weight gain, alertness

Parameter Recommendation

Starting dose 0.25 mg once or twice daily

Titration Increase by no more than 0.25 mg every 5–7 days

Maximum recommended 2 mg/day (lower than general adult maximum)

Increased Risks Falls, fractures, oversedation, cognitive impairment, paradoxical reactions, delirium

Additional Precautions Avoid long-term use; consider safer alternatives (SSRIs, buspirone) for chronic anxiety; regular reassessment mandatory

Interacting Drug Mechanism Effect Management

Ketoconazole, Itraconazole Strong CYP3A4 inhibition Markedly increased alprazolam levels; severe sedation risk Contraindicated — avoid combination

Ritonavir, Cobicistat Strong CYP3A4 inhibition Significantly increased alprazolam exposure Contraindicated — avoid combination

Opioids (morphine, tramadol, fentanyl) Additive CNS depression Profound sedation, respiratory depression, coma, death Avoid if possible; if essential, reduce doses of both and monitor closely

Alcohol Additive CNS depression Severe sedation, respiratory depression, psychomotor impairment Avoid concurrent use; counsel patient

Fluvoxamine CYP3A4 inhibition Increased alprazolam levels (2–3 fold) Reduce alprazolam dose by 50%; monitor closely

Interacting Drug Effect Management

Clarithromycin, Erythromycin Moderate CYP3A4 inhibition; increased alprazolam levels Monitor for increased sedation; consider dose reduction

Fluconazole Moderate CYP3A4 inhibition Monitor clinical response; may need dose adjustment

Carbamazepine, Phenytoin CYP3A4 induction; reduced alprazolam efficacy May need higher alprazolam doses; monitor for breakthrough anxiety

Rifampicin Strong CYP3A4 induction Significantly reduced alprazolam efficacy

Theophylline May antagonise sedative effect Monitor for reduced anxiolytic efficacy

Digoxin Possible increased digoxin levels (especially in elderly) Monitor digoxin levels in elderly patients

Cimetidine Inhibits hepatic metabolism Monitor for increased sedation

Other CNS depressants (antihistamines, antipsychotics) Additive sedation Use with caution; monitor for oversedation

• Drowsiness, sedation

• Fatigue, lethargy

• Dizziness, lightheadedness

• Impaired coordination, ataxia

• Memory impairment, anterograde amnesia

• Dry mouth

• Headache

• Blurred vision

• Constipation

• Changes in libido

Adverse Effect Clinical Action

Physical dependence and withdrawal syndrome (anxiety, insomnia, tremors, seizures) Taper gradually over weeks; never discontinue abruptly after prolonged use

Respiratory depression (especially with opioids/alcohol) Discontinue; supportive care; flumazenil if severe (use with caution)

Paradoxical reactions (agitation, aggression, hostility, disinhibition) Discontinue immediately; more common in elderly and children

Suicidal ideation (in depressed patients) Close monitoring; psychiatric evaluation

Seizures (on abrupt discontinuation) Hospitalisation may be required; reinstitute benzodiazepine and taper slowly

Severe hypotension Supportive care; IV fluids

Angioedema (rare) Discontinue permanently; emergency management

After initiation (1–2 weeks) Sedation level, efficacy, behavioural changes, signs of dependence

Long-term (if continued) Reassess need for continuation every 2–4 weeks; monitor for tolerance, dependence, cognitive impairment

On discontinuation Taper over 2–4 weeks minimum (longer if prolonged use); monitor for withdrawal symptoms (anxiety, insomnia, tremor, seizures)

• Restyl™ (Cipla) — 0.25 mg, 0.5 mg, 1 mg tablets

• Alprax™ (Torrent) — 0.25 mg, 0.5 mg, 1 mg tablets

• Trika™ (Unichem) — 0.25 mg, 0.5 mg tablets

• Alzolam™ (Micro Labs) — 0.25 mg, 0.5 mg, 1 mg tablets

• Zolax™ (Sun Pharma) — 0.25 mg, 0.5 mg tablets

• Anxit™ (Micro Labs) — 0.25 mg, 0.5 mg tablets

• Alprazolam SR / XR (various) — extended-release formulations

Fixed-Dose Combinations (FDCs):

• FDCs with antidepressants exist but are not routinely recommended outside specialist psychiatry

0.25 mg tablet ₹1.50–₹3.00 per tablet —

0.5 mg tablet ₹2.00–₹5.00 per tablet —

Regulatory: Not listed under NLEM 2022; not under NPPA price control; prices vary by brand and region

1. Not first-line for chronic anxiety — SSRIs (escitalopram, sertraline) are preferred for long-term anxiety management; reserve alprazolam for short-term use or acute exacerbations

1. Short half-life issue — Rebound anxiety and interdose withdrawal common; consider extended-release formulation or longer-acting benzodiazepine (clonazepam) for panic disorder if frequent dosing problematic

1. Taper slowly on discontinuation — Reduce by 0.25–0.5 mg every 3–5 days; withdrawal seizures can occur with abrupt cessation after >2 weeks of regular use

1. Elderly prescribing — Start very low (0.25 mg), titrate slowly; strongly associated with falls, fractures, and cognitive decline; avoid if possible

1. Dependence risk counselling — Warn patients about dependence with use beyond 2–4 weeks; avoid in patients with substance use history

1. Driving and machinery warning — Mandatory counselling; impairment may persist even without subjective sedation

anxiolytic; benzodiazepine; panic-disorder; GAD; short-acting; dependence-risk; elderly-caution; hepatic-caution; pregnancy-avoid; Schedule-H; psychiatric-use

RxIndia v1.0 — 07 May 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine

• AIIMS Psychiatry Prescribing Protocols

• Indian Psychiatric Society Consensus Statements

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• WHO Essential Medicines List (supportive reference for paediatric considerations)