Schedule H

Oral, Intravenous (IV), Intramuscular (IM), Topical

• Tablet: 25 mg, 50 mg

• Syrup: 12.5 mg/5 mL

• Injection: 50 mg/mL (1 mL ampoule)

• Topical cream/lotion: 2%

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Allergic Conditions (Allergic Rhinitis, Urticaria, Angioedema)

Parameter Details

Starting dose 25 mg orally every 6–8 hours

Titration Increase to 50 mg per dose based on response and tolerability

Usual maintenance dose 75–150 mg/day in divided doses (TDS or QDS)

Maximum dose 300 mg/day (short-term use only)

Clinical notes:

• Second-generation antihistamines preferred for chronic allergic conditions due to less sedation

• Injectable route (IM/IV) reserved for acute severe urticaria or angioedema in emergency settings

• Significant sedation limits daytime use

1. Motion Sickness (Prophylaxis and Treatment)

Parameter Details

Starting dose 25–50 mg orally, 30 minutes before travel

Titration Not applicable

Usual maintenance dose 25–50 mg every 4–6 hours as needed

Maximum dose 150 mg/day

Clinical notes:

• Most effective when administered prophylactically before travel

• Significant sedation expected; warn patient against driving or operating machinery

1. Insomnia (Short-term Management Only)

Parameter Details

Starting dose 25 mg orally at bedtime

Titration May increase to 50 mg if needed

Usual maintenance dose 25–50 mg at bedtime

Maximum dose 50 mg/day

Clinical notes:

• Limit use to ≤7–10 days to prevent tolerance and avoid anticholinergic burden

• Not recommended for chronic insomnia management

• Non-pharmacological sleep hygiene measures should be first-line

1. Anaphylaxis (Adjunctive Therapy)

Parameter Details

Starting dose 25–50 mg IV slowly over 2–3 minutes OR deep IM

Titration Not applicable

Usual maintenance dose May repeat every 4–6 hours as needed

Maximum dose 400 mg/24 hours (parenteral)

Clinical notes:

• NEVER use as monotherapy for anaphylaxis — always administer with intramuscular adrenaline as first-line

• Adjunctive role only; used alongside adrenaline and corticosteroids

• IV route requires slow administration with monitoring for hypotension

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes

Drug-induced extrapyramidal symptoms (acute dystonia) 25–50 mg orally or IM, 2–4 times daily Short-term until symptoms resolve OFF-LABEL; Specialist only; Evidence: Standard psychiatry/neurology practice

Cough (antitussive adjunct) 25 mg orally every 6 hours Short-course only (≤5 days) OFF-LABEL; Often used in combination products; Limited evidence

PAEDIATRIC DOSING (Specialist Only)

⚠️ NOT RECOMMENDED in children below 2 years of age due to risk of respiratory depression, paradoxical excitation, and seizures — except under specialist/emergency supervision.

Primary Indications (Approved / Standard in India)

1. Allergic Conditions (Urticaria, Allergic Rhinitis)

2–6 years 6.25 mg orally (2.5 mL syrup) Every 4–6 hours 37.5 mg/day

6–12 years 12.5–25 mg orally Every 6–8 hours 150 mg/day

12 years 25–50 mg orally Every 6–8 hours 300 mg/day

Titration: Adjust based on clinical response; use lowest effective dose

Clinical notes:

• Monitor for sedation and paradoxical excitation (more common in younger children)

• Injectable form reserved for emergency/specialist settings only

• Prefer second-generation antihistamines for chronic allergic conditions in children

1. Motion Sickness (Prophylaxis)

2–6 years 6.25 mg orally 30 minutes before travel; repeat every 6 hours if needed (max 2 doses/day)

6–12 years 12.5–25 mg orally 30 minutes before travel; repeat every 6 hours if needed (max 3 doses/day)

12 years 25–50 mg orally 30 minutes before travel; repeat every 4–6 hours if needed

Secondary Indications — Paediatric Doses (Off-label)

Indication Dose Age Notes

Acute dystonia (drug-induced extrapyramidal symptoms) 1–2 mg/kg/dose IM or IV >2 years OFF-LABEL; Maximum 50 mg per dose; Emergency/Specialist only; Evidence: Paediatric emergency practice

⚠️ Safety Monitoring:

• Respiratory rate and effort (especially in younger children)

• Level of sedation

• Signs of paradoxical excitation (agitation, hyperactivity)

• Anticholinergic effects (dry mouth, urinary retention)

Dialysis Not significantly dialyzed; use lower doses with monitoring

• Known hypersensitivity to diphenhydramine or other ethanolamine antihistamines

• Narrow-angle glaucoma (risk of precipitating acute angle-closure)

• Symptomatic benign prostatic hyperplasia or bladder neck obstruction

• Acute asthma attack (may thicken bronchial secretions)

• Neonates and premature infants

• Concurrent use with MAO inhibitors (within 14 days)

• Breastfeeding mothers using topical application on breasts

• Elderly patients (increased anticholinergic sensitivity, fall risk, cognitive impairment)

• Epilepsy or seizure disorders (may lower seizure threshold)

• Cardiovascular disease (may cause tachycardia, hypotension)

• Hepatic or renal impairment

• Patients with pyloroduodenal obstruction

• Patients operating machinery or driving (significant sedation)

• Concurrent use of other CNS depressants

• Hyperthyroidism

• Stenosing peptic ulcer

Parameter Details

Risk category Category B (generally considered low risk for short-term use)

General safety Limited human data; no clear teratogenicity in observational studies

Preferred use Short courses for allergic conditions or nausea under obstetrician supervision

Preferred alternatives Chlorpheniramine, Loratadine, or Cetirizine for allergies

Monitoring Avoid near term (third trimester) — risk of neonatal CNS depression and withdrawal; monitor fetal movements

Parameter Details

Compatibility Generally compatible for short-term use

Drug levels in milk Low

Infant monitoring Sedation, irritability, poor feeding, unusual drowsiness

Preferred alternatives Loratadine or Cetirizine preferred for long-term allergy management

Caution May reduce milk production due to anticholinergic effects

Parameter Recommendation

Starting dose 12.5–25 mg once or twice daily

Titration Slow; increase only after 48–72 hours if tolerated

Specific risks Falls, excessive sedation, confusion, paradoxical agitation, urinary retention, constipation, cognitive impairment

Recommendation Listed in Beers Criteria as potentially inappropriate; avoid routine use in elderly; prefer second-generation antihistamines when feasible

Interacting Drug/Class Effect Recommendation

MAO inhibitors Severe anticholinergic toxicity, hypertensive crisis, CNS excitation Contraindicated — avoid within 14 days of MAOI use

CNS depressants (opioids, benzodiazepines, alcohol, barbiturates) Additive sedation and respiratory depression Avoid combination or significantly reduce doses; close monitoring required

Anticholinergic drugs (TCAs, atropine, oxybutynin, ipratropium) Increased anticholinergic toxicity (urinary retention, constipation, delirium, hyperthermia) Avoid combination in elderly; monitor closely if essential

QT-prolonging drugs Potential additive QT prolongation at high doses Monitor ECG if combination unavoidable

Interacting Drug/Class Effect Recommendation

SSRIs (fluoxetine, sertraline, paroxetine) Additive CNS effects; CYP2D6 inhibition may increase diphenhydramine levels Monitor for increased sedation

Levodopa Anticholinergic antagonism may reduce levodopa efficacy Avoid if possible; monitor Parkinson's control

Metoclopramide Antagonism of prokinetic effect Avoid concurrent use if possible

Antihypertensives Additive hypotensive effects Monitor blood pressure

Phenytoin Potential increased CNS depression Monitor closely

• Sedation / drowsiness (very common)

• Dry mouth

• Dizziness / light-headedness

• Blurred vision

• Constipation

• Urinary hesitancy / retention

• Impaired coordination and concentration

• Thickening of bronchial secretions

Adverse Effect Clinical Notes

Respiratory depression Especially in children <2 years and with overdose — avoid in this age group

Seizures In overdose or patients with low seizure threshold

Cardiac arrhythmias High doses or rapid IV administration; QT prolongation possible

Acute angle-closure glaucoma In predisposed individuals — discontinue and seek ophthalmology review

Paradoxical excitation Hyperactivity, agitation, especially in children — discontinue if occurs

Severe hypotension With rapid IV administration

Haemolytic anaemia Rare; discontinue if confirmed

Phase Parameters

Baseline Cognitive status (especially in elderly), history of glaucoma, prostate symptoms, seizure history

After initiation Sedation level, anticholinergic side effects, blood pressure (parenteral use) within 48–72 hours

Long-term Not recommended for chronic use; reassess need if use extends beyond 7–10 days

Special Respiratory rate and pattern if using IV/IM route, especially in children and elderly

• Benadryl (Johnson & Johnson) — most widely recognized

• Histafree

• Caladryl (topical, combination with calamine)

• Various generic formulations

• Available in numerous combination cough and cold syrups (caution: check for duplication)

Note: NOT included in NLEM 2022; prices not NPPA-controlled; significant brand variation exists.

1. Highly sedating — Not suitable for patients requiring alertness; always warn about driving and machinery operation.

1. Not for chronic insomnia — Tolerance develops rapidly; limit use to 7–10 days maximum; emphasize non-pharmacological sleep hygiene measures.

1. Avoid in elderly — Listed in Beers Criteria as potentially inappropriate due to high anticholinergic burden and fall risk; prefer second-generation antihistamines.

1. Paradoxical excitation in children — More common at doses >25 mg; monitor closely and discontinue if agitation occurs.

1. Check combination products — Commonly included in OTC "cold and cough" syrups; risk of accidental duplication and overdose.

1. Adjunctive only in anaphylaxis — Never replace intramuscular adrenaline; diphenhydramine is only supportive therapy.

diphenhydramine; antihistamine; first-generation; sedation; urticaria; motion sickness; insomnia; anaphylaxis-adjunct; anticholinergic; elderly-caution; paediatrics-caution; Schedule H

RxIndia v1.0 — 09 Jan 2025

• CDSCO (Formulations and Schedule H listing)

• Indian Pharmacopoeia (IP 2018)

• API Textbook of Medicine

• IAP Guidelines — Paediatric Allergy and Drug Dosing

• AIIMS Treatment Protocols for Anaphylaxis

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO EML (supportive for paediatric dosing)

• CIMS India (Brand verification)