Schedule H

Oral

Form Strengths

Capsules 10 mg

Note: Limited availability in India; primarily stocked by tertiary care hospitals and specialty pharmacies for pre-operative phaeochromocytoma management.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Phaeochromocytoma — Pre-operative Alpha-Blockade and Symptomatic Control

Setting: Specialist supervision (endocrinology/endocrine surgery); preferably inpatient initiation

Parameter Dose

Starting dose 10 mg orally once or twice daily

Titration Increase by 10 mg every 1–2 days based on blood pressure response and orthostatic symptoms

Usual maintenance dose 20–40 mg/day in 2–3 divided doses

Maximum dose 100 mg/day (rarely required; use under specialist supervision only)

Clinical Notes:

• Initiate 10–14 days prior to planned surgery to allow complete alpha-blockade

• Concurrent liberal salt and fluid intake recommended to counteract volume contraction from catecholamine excess

• Beta-blocker (e.g., propranolol 10–40 mg TDS) may be added ONLY AFTER adequate alpha-blockade is established (typically after 2–3 days of phenoxybenzamine) to control reflex tachycardia

• Never initiate beta-blocker before alpha-blockade — risk of severe hypertensive crisis from unopposed alpha stimulation

• Target pre-operative BP: Seated BP <130/80 mmHg; orthostatic drop SBP >20 mmHg (indicates adequate blockade)

1. Inoperable or Metastatic Phaeochromocytoma — Long-term Symptomatic Control

Parameter Dose

Starting dose 10 mg orally twice daily

Titration Increase by 10–20 mg every few days to weeks based on symptom control and tolerability

Usual maintenance dose 40–60 mg/day in 2–3 divided doses

Maximum dose 100 mg/day

Clinical Notes:

• Long-term use for palliation in unresectable tumours

• Requires ongoing monitoring for postural hypotension and volume status

• Beta-blocker co-administration usually required for tachycardia control

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes Evidence Basis

Complex regional pain syndrome (CRPS) / Reflex sympathetic dystrophy — OFF-LABEL Starting: 10 mg orally once daily; Titration: Increase by 10 mg every 3–5 days; Maintenance: 20–40 mg/day in divided doses Trial for 4–8 weeks; continue if beneficial Specialist only (pain medicine); used when sympathetic blockade desired Small case series; limited India-specific data

Autonomic dysreflexia in spinal cord injury — OFF-LABEL Starting: 10 mg orally once or twice daily; Maintenance: 20–30 mg/day in divided doses Long-term prophylaxis in recurrent cases Specialist only (rehabilitation medicine/neurology); used in resistant cases Small trials; Indian specialist practice

Benign prostatic hyperplasia (BPH) — OFF-LABEL 10–20 mg/day in divided doses Trial for 4–6 weeks Rarely used; better alternatives available (tamsulosin, alfuzosin) Historical use; largely superseded

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Phaeochromocytoma — Pre-operative Alpha-Blockade

Setting: Paediatric endocrinology/endocrine surgery supervision; inpatient initiation mandatory

Parameter Weight-based Dosing

Starting dose 0.2 mg/kg/day orally in 2–3 divided doses

Titration Increase by 0.2 mg/kg/day every 1–2 days based on blood pressure and tolerability

Usual maintenance dose 0.4–0.6 mg/kg/day in 2–3 divided doses

Maximum dose 1 mg/kg/day (not exceeding 100 mg/day)

Clinical Notes:

• Initiate 10–14 days before planned surgery

• Add beta-blocker only after adequate alpha-blockade established

• Liberal salt and fluid intake during preparation

Safety Monitoring:

• Supine and standing blood pressure at least twice daily

• Heart rate monitoring

• Watch for nasal congestion, excessive sedation, syncope

• Daily weight to assess volume status

Secondary Indications — Paediatric (Off-label)

Not applicable — No established off-label paediatric indications documented in Indian practice.

Age Restriction Statement:

• Not recommended in children <1 year of age

• Use in children ≥1 year only under paediatric endocrine surgery/endocrinology specialist supervision in tertiary centres

Mild–moderate impairment No dose adjustment required

Note: Phenoxybenzamine is hepatically metabolised; effects may be prolonged and intensified in hepatic impairment.

Known hypersensitivity to phenoxybenzamine

• Hypotension from any cause other than catecholamine excess (e.g., hypovolaemic shock, septic shock)

• Conditions where a fall in blood pressure may be hazardous (e.g., recent cerebrovascular event, severe coronary artery disease with unstable angina)

• Concurrent use with PDE5 inhibitors (sildenafil, tadalafil, vardenafil)

• Coronary artery disease (reflex tachycardia may precipitate angina or ischaemia)

• Cerebrovascular disease

• Elderly patients (enhanced sensitivity to hypotensive effects; increased fall risk)

• Volume depletion or dehydration (correct before initiation)

• Congestive heart failure (risk of worsening due to reflex tachycardia and fluid shifts)

• Respiratory infection (nasal congestion may worsen symptoms)

• Renal impairment with volume depletion

• Concurrent use of other antihypertensives (additive hypotension)

Parameter Detail

Risk Category No formal India classification; limited human data; use only if clearly indicated

Overall Safety Crosses placenta; may cause neonatal hypotension; animal studies inconclusive

Preferred Alternatives Doxazosin or prazosin more commonly used in pregnancy-associated phaeochromocytoma in Indian practice

When May Be Used Pregnancy with phaeochromocytoma when surgical resection not feasible in first trimester; use under combined endocrinology and maternal-fetal medicine supervision

Monitoring Frequent maternal BP (supine and standing); fetal heart rate monitoring; serial fetal growth assessment; neonatal BP monitoring after delivery

Parameter Detail

Compatibility Not recommended; avoid if alternative available

Expected Milk Levels Unknown; likely low to moderate (lipophilic, long half-life)

Preferred Alternatives If alpha-blockade needed postpartum, doxazosin or prazosin preferred

Infant Monitoring If breastfeeding unavoidable: monitor infant for hypotonia, poor feeding, excessive drowsiness, hypotension signs

Parameter Recommendation

Starting dose 10 mg orally once daily (not twice daily)

Titration Slower increments; increase by 10 mg every 3–4 days (not every 1–2 days)

Special Risks Exaggerated hypotensive response; high risk of orthostatic hypotension and falls; dizziness and syncope; age-related reduction in baroreceptor sensitivity

Monitoring Supine and standing BP at each visit; assess for falls; ensure adequate hydration

Additional Precautions Inpatient initiation strongly recommended; avoid rapid dose escalation

Interacting Drug/Class Effect Management

Beta-blockers (when initiated before alpha-blockade) Unopposed alpha-adrenergic stimulation can cause severe hypertensive crisis in phaeochromocytoma Never initiate beta-blocker before adequate alpha-blockade is established (minimum 2–3 days of phenoxybenzamine)

PDE5 inhibitors (sildenafil, tadalafil, vardenafil) Profound additive hypotension Contraindicated; avoid concurrent use

Adrenaline (epinephrine) Paradoxical hypotension due to alpha-blockade with unopposed beta2 vasodilation (epinephrine reversal) Avoid if possible; if adrenaline required, be aware of this effect; use noradrenaline preferentially for vasopressor support

Other alpha-blockers (prazosin, doxazosin, tamsulosin) Additive alpha-blockade; severe hypotension Avoid combination

Interacting Drug/Class Effect Management

Other antihypertensives (ACE inhibitors, ARBs, CCBs, diuretics) Additive hypotensive effect Can be used together if needed; monitor BP closely; adjust doses as required

Antipsychotics (chlorpromazine, haloperidol) Enhanced hypotensive effect (alpha-blocking properties of phenothiazines) Monitor BP; use lower doses

Tricyclic antidepressants (amitriptyline, imipramine) May enhance orthostatic hypotension Monitor for postural symptoms

Alcohol Additive CNS depression and hypotension Counsel patient to limit alcohol intake

Opioid analgesics Additive hypotension Monitor BP; particularly relevant peri-operatively

General anaesthetics Enhanced hypotensive response Anaesthetist must be informed of phenoxybenzamine use; careful BP management intra-operatively

• Postural (orthostatic) hypotension

• Nasal congestion/stuffiness (due to alpha-blockade of nasal vasculature)

• Reflex tachycardia

• Miosis (pupillary constriction)

• Fatigue, drowsiness, sedation

• Dizziness, lightheadedness

• Nausea, vomiting

• Inhibition of ejaculation (retrograde ejaculation)

Adverse Effect Clinical Notes

Severe orthostatic hypotension with syncope May occur especially during initial titration; ensure adequate hydration; reduce dose or discontinue if recurrent

Prolonged hypotension Due to irreversible alpha-blockade (half-life 24 hours, but receptor blockade lasts 3–4 days); supportive care with IV fluids and vasopressors if severe; noradrenaline preferred over adrenaline

Tachyarrhythmias Reflex tachycardia can precipitate arrhythmias in susceptible patients; add beta-blocker after adequate alpha-blockade

Myocardial ischaemia In patients with coronary artery disease; due to reflex tachycardia and hypotension

Cerebrovascular event In patients with pre-existing cerebrovascular disease; due to hypotension

During initiation/titration Daily supine and standing BP; heart rate; symptoms of orthostatic hypotension (dizziness, syncope); daily weight; nasal congestion; sedation level

Pre-operatively Confirm adequate alpha-blockade: target seated BP <130/80 mmHg with orthostatic drop; absence of ST-T changes on ECG; haematocrit (haemodilution indicates volume expansion)

Long-term (if on chronic therapy) BP every 1–2 weeks initially, then monthly; symptom assessment; renal function periodically

Phenoxybenzamine capsules Various (imports/hospital supply) 10 mg

Note: Availability is limited; often procured through hospital pharmacy channels or specialty importers for tertiary care centres. Dibenyline® (international brand) may be available through import.

Note: Not included in NLEM 2022; not under NPPA price control. Prices variable depending on source (hospital procurement vs specialty pharmacy). Government supply limited to select tertiary centres with endocrine surgery units.

1. Sequence of blockade is critical — Always establish adequate alpha-blockade with phenoxybenzamine for at least 2–3 days BEFORE adding beta-blocker; reversing this sequence can cause catastrophic hypertensive crisis in phaeochromocytoma

1. Plan for prolonged effect — Due to irreversible receptor binding, the effect of phenoxybenzamine persists for 3–4 days after discontinuation; anticipate and plan for this during peri-operative management

1. Volume expansion is essential — Encourage liberal salt and fluid intake during pre-operative preparation; catecholamine-induced vasoconstriction causes chronic volume contraction; adequate volume expansion reduces intra-operative hypotension risk

1. Orthostatic hypotension is expected — Counsel patients about rising slowly from sitting/lying position; first-dose effect can be pronounced; consider inpatient initiation for high-risk patients

1. Nasal congestion is not allergic — This common side effect results from alpha-blockade of nasal vasculature; reassure patients; decongestants are generally ineffective and may be contraindicated

1. Use noradrenaline, not adrenaline, for hypotension — If vasopressor support needed peri-operatively, noradrenaline is preferred; adrenaline may cause paradoxical hypotension (epinephrine reversal) due to alpha-blockade leaving beta2 vasodilation unopposed

phenoxybenzamine; alpha-blocker; phaeochromocytoma; pheochromocytoma; pre-operative preparation; irreversible blockade; antihypertensive; endocrine surgery; catecholamine excess; specialist use; limited availability India

RxIndia v1.0 — 10 Jan 2025

• CDSCO drug information

• Indian Pharmacopoeia 2018

• National Formulary of India

• API Textbook of Medicine

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• AIIMS Endocrine Surgery protocols for phaeochromocytoma

• Indian Association of Endocrine Surgeons practice standards

• Endocrine Society Clinical Practice Guidelines (supportive reference)