Schedule H (Prescription only)

Inhalation, Intravenous (IV – hospital use only)

• Inhalation solution: 10 µg/mL (2 mL ampoules)

• Intravenous infusion concentrate: 50 µg/0.5 mL (hospital supply only)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Pulmonary Arterial Hypertension (PAH) — Inhalation Route

Used in idiopathic PAH or PAH associated with connective tissue disease (WHO Group 1 PAH).

Parameter Details

Starting dose 2.5 µg via nebuliser (tolerance test)

Titration Increase to 5 µg per inhalation if well tolerated

Usual maintenance dose 5 µg per inhalation, 6–9 times daily at 2–3 hour intervals during waking hours

Maximum dose 45 µg/day (equivalent to 9 inhalations of 5 µg each)

Clinical Notes:

• Use only with approved nebuliser devices (e.g., I-Neb, Prodose AAD systems)

• Standard jet nebulisers are NOT suitable

• Monitor blood pressure before and after each inhalation

• Administer in upright sitting position

1. Peripheral Arterial Occlusive Disease (Critical Limb Ischaemia) — IV Route

Reserved for cases refractory to standard vasodilator therapy. Specialist and hospital use only.

Parameter Details

Starting dose 0.5 ng/kg/min IV infusion

Titration Increase gradually based on tolerability (monitor for headache, hypotension)

Usual maintenance dose 1–2 ng/kg/min over 6 hours daily

Maximum dose 2 ng/kg/min (up to 3–4 ng/kg/min only under ICU monitoring in exceptional cases)

Duration 5–14 days depending on clinical response

Clinical Notes:

• Requires specialist vascular surgery or medicine supervision

• Continuous BP and cardiac monitoring during infusion mandatory

• Dilute in normal saline before administration

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Raynaud's Phenomenon (refractory to standard therapy) 0.5–2 ng/kg/min IV infusion over 6 hours daily 3–5 days OFF-LABEL. Specialist only (Rheumatology). Evidence: European RCTs; used in tertiary Indian centres under rheumatology supervision.

PAEDIATRIC DOSING (Specialist Only)

⚠️ All paediatric use of iloprost is off-label in India. Restricted to tertiary paediatric cardiology or PICU settings.

Primary Indication: Pulmonary Arterial Hypertension — Inhalation Route

Age: ≥1 year (specialist paediatric cardiology supervision mandatory)

Parameter Details

Starting dose 2.5 µg per inhalation

Titration Increase to 5 µg per inhalation if tolerated

Usual maintenance dose 2.5–5 µg per inhalation, 3–9 times daily at 2–3 hour intervals during waking hours

Maximum dose 45 µg/day

Safety Monitoring:

• Monitor systemic blood pressure closely, especially in infants and younger children

• Watch for signs of hypotension (pallor, lethargy, poor feeding)

• Pulse oximetry during initial doses

Secondary Indications — Paediatrics (Off-label)

• Not routinely recommended

• IV use: Only under PICU or paediatric cardiology specialist supervision in exceptional circumstances

Age Restriction: NOT recommended below 1 year of age except under specialist supervision with compelling clinical indication.

CrCl >30 mL/min No dose adjustment required

CrCl <30 mL/min Use with caution; start at lower end of dosing range with slower titration

Haemodialysis Limited data; not significantly dialysed but enhanced drug sensitivity possible

Note: Iloprost is not primarily cleared renally, but patients with severe renal impairment may have enhanced sensitivity to hypotensive effects.

• Known hypersensitivity to iloprost or any excipient

• Pulmonary hypertension due to left heart disease (WHO Group 2 PH)

• Pulmonary hypertension due to chronic thromboembolic disease (WHO Group 4 PH)

• Conditions with high bleeding risk:

• Active peptic ulcer

• Recent trauma

• Intracranial haemorrhage within 3 months

• Severe coronary artery disease or unstable angina

• Myocardial infarction within preceding 6 months

• Decompensated heart failure (unless under close specialist supervision)

• Pregnancy (IV use contraindicated)

• Pre-existing hypotension (systolic BP <85 mmHg)

• Concurrent use of anticoagulants or antiplatelet agents (bleeding risk)

• Obstructive airways disease (asthma, COPD) — may trigger bronchospasm with inhaled route

• Patients prone to syncope

• Concurrent use of other vasodilators or antihypertensives

• Improper nebuliser device — can result in inadequate drug delivery or overdose

• History of orthostatic hypotension

Parameter Details

Risk category Category C (animal studies show adverse effects; no adequate human studies)

Recommendation Avoid unless life-threatening condition with no alternatives; specialist obstetric and cardiology input essential

Preferred alternatives Sildenafil may be considered for PAH in pregnancy under specialist guidance

Monitoring Maternal blood pressure, uterine perfusion (Doppler), fetal growth, fetal heart rate

Note: IV use is contraindicated in pregnancy. Inhaled route may be considered only if absolutely necessary with close maternal-fetal monitoring.

Parameter Details

Compatibility Limited data available

Expected milk levels Likely low due to rapid metabolism and short half-life

Inhaled route May be acceptable with infant monitoring

IV route Avoid unless essential; consider temporary cessation of breastfeeding during IV course

Infant monitoring Observe for irritability, feeding difficulties, poor weight gain

Parameter Recommendation

Starting dose Use lowest effective dose (2.5 µg inhaled or 0.5 ng/kg/min IV)

Titration Slower titration recommended

Key risks Orthostatic hypotension, dizziness, falls, syncope

Monitoring Blood pressure (lying and standing), renal function, hydration status

Note: Elderly patients may have reduced baroreceptor sensitivity and are more susceptible to hypotensive adverse effects.

Drug/Class Interaction Management

Nitrates (isosorbide dinitrate, glyceryl trinitrate) Synergistic vasodilation causing severe hypotension AVOID concurrent use

PDE-5 inhibitors (sildenafil, tadalafil) Additive hypotensive effect Use combination with extreme caution; close BP monitoring; may need dose reduction of one or both agents

Other prostacyclin analogues (epoprostenol, treprostinil) Overlapping pharmacology; increased bleeding and hypotension risk Avoid concurrent use unless transitioning under specialist supervision

Thrombolytics Markedly increased bleeding risk Avoid concurrent administration

Drug/Class Interaction Management

Antihypertensives (ACE inhibitors, ARBs, beta-blockers, CCBs) Additive hypotensive effect Monitor BP; consider dose adjustment

Anticoagulants (warfarin, heparin, DOACs) Increased bleeding tendency Monitor for bleeding; check INR if on warfarin

Antiplatelet agents (aspirin, clopidogrel) Additive antiplatelet effect; bleeding risk Use with caution; clinical monitoring

NSAIDs Combined effect on platelet function Monitor for GI and other bleeding

SSRIs (sertraline, fluoxetine) May enhance bleeding tendency Monitor with chronic co-administration

Diuretics Synergistic hypotension BP monitoring; hydration assessment

Bosentan Often used in combination for PAH Monitor BP, hepatic function

• Flushing (facial warmth, redness)

• Headache

• Cough (especially with inhaled route)

• Jaw pain or trismus

• Nausea

• Hypotension

• Throat irritation (inhaled route)

• Diarrhoea

Adverse Effect Notes

Severe hypotension May require fluid resuscitation, vasopressors, or drug discontinuation

Syncope Particularly in PAH patients; risk of injury from falls

Bronchospasm Especially in patients with asthma or COPD; may require bronchodilator rescue

Significant bleeding GI haemorrhage, intracranial bleeding (rare); more common with IV route and concurrent anticoagulation

Pulmonary oedema If used inappropriately in left heart disease

Thrombocytopenia Rare; monitor if prolonged IV use

After initiation BP and heart rate post-inhalation for first few doses; observe for bronchospasm, flushing, syncope

During IV infusion Continuous BP and cardiac monitoring; watch for signs of bleeding

Long-term Periodic BP assessment, 6-minute walk test (for PAH efficacy), functional class evaluation, hepatic and renal function

• Ventavis® (Inhalation solution) — Bayer Zydus Pharma

• Ilomedine® (IV formulation) — Janssen/Johnson & Johnson (hospital distribution)

Note: Not included in NLEM. High out-of-pocket cost. Primarily available through hospital pharmacy channels. Not suitable for resource-limited or primary care settings.

1. Device matters: Always use compatible nebuliser systems (I-Neb AAD, Prodose AAD). Standard jet or ultrasonic nebulisers lead to inconsistent drug delivery and potential overdose or underdose.

1. Posture during inhalation: Patients should sit upright while inhaling to minimise bronchospasm and optimise drug deposition.

1. Not interchangeable: Iloprost provides acute pulmonary vasodilation; it cannot substitute oral agents (sildenafil, bosentan) for sustained disease modification in PAH.

1. Frequency discipline: Do not exceed 9 inhalations per day. Excessive dosing increases risk of hypotension, flushing, and syncope without added benefit.

1. Not first-line in resource-limited settings: Due to complex delivery requirements and cost, iloprost is reserved for specialist centres. Oral PAH therapies are more practical in most Indian settings.

1. Combination therapy in PAH: Often used alongside oral endothelin receptor antagonists (bosentan) or PDE-5 inhibitors (sildenafil) as part of goal-directed combination therapy.

iloprost; pulmonary-hypertension; PAH; prostacyclin-analogue; inhaled-vasodilator; peripheral-vascular-disease; critical-limb-ischaemia; Raynaud-phenomenon; specialist-use; NLEM-no

RxIndia v1.1 — 10 Jan 2025

• CDSCO approved product information

• Indian Pharmacopoeia 2018

• National Formulary of India 2021

• AIIMS Hospital Formulary (IV administration protocol)

• API Textbook of Medicine (11th Edition, 2022)

• ICMR guidance documents on pulmonary hypertension (where available)

• European RCTs on IV iloprost in Raynaud's phenomenon (cited for off-label use only)

• Indian tertiary care specialist practice protocols (cardiology, rheumatology)