Iloprost

Iloprost is a prostacyclin analogue given by inhalation for pulmonary arterial hypertension (group 1), functional class III, and intravenously for severe peripheral vasospasm in systemic sclerosis. The inhaled route delivers drug to the pulmonary vessels with less systemic effect. Start only in a PAH centre.

Classification. Prostacyclin analogue (prostanoid), vasodilator, antiplatelet.

Mechanism. Stimulates prostacyclin receptors, raising cyclic AMP in vascular smooth muscle and platelets, causing vasodilatation and inhibiting platelet aggregation.

Pharmacokinetics. Inhaled onset within minutes, with effect lasting 30 to 90 minutes. Metabolised by beta-oxidation. Half-life 20 to 30 minutes. Excreted in urine and faeces.

Specialist, PAH, adults, inhaled. Start 2.5 micrograms at the mouthpiece. If tolerated, increase to 5 micrograms. Inhale 6 to 9 times daily while awake, as needed and tolerated. Maximum 45 micrograms daily (9 inhalations of 5 micrograms). Each inhalation takes 4 to 10 minutes.

Specialist, severe Raynaud phenomenon or digital ulcers in systemic sclerosis, intravenous. 0.5 to 2 ng/kg/minute for 6 hours each day for 3 to 5 days, titrated to tolerance.

Alternative. Other prostanoids or an oral add-on when frequent daily inhalation is not workable.

Emergency. Not used.

Titration and loading. One step from 2.5 to 5 micrograms. No loading dose.

Contraindications. Conditions in which platelet effects raise bleeding risk (active peptic ulcer, trauma, intracranial haemorrhage), severe coronary heart disease or unstable angina, myocardial infarction in the past 6 months, decompensated heart failure, severe arrhythmia, stroke in the past 3 months, pulmonary hypertension from venous occlusion, valvular disease with myocardial dysfunction.

Serious adverse effects. Syncope from hypotension, bronchospasm, haemoptysis and bleeding, rebound pulmonary hypertension if stopped suddenly.

Common adverse effects. Cough, flushing, headache, jaw pain, nausea, hypotension, dizziness.

Interactions. Anticoagulants and antiplatelets raise bleeding risk. Vasodilators and antihypertensives add hypotension.

Common prescribing errors. Using a general-purpose nebuliser instead of the dedicated device. Missing the inhalation frequency. Starting at 5 micrograms.

Special groups.

• Pregnancy: avoid unless the benefit outweighs risk. Breastfeeding: no data; caution.

• Older adults: titrate with care.

• Kidney impairment: in dialysis-dependent patients, start 2.5 micrograms with dosing intervals of 3 to 4 hours. Liver impairment: in Child-Pugh B or C, start 2.5 micrograms with dosing intervals of 3 to 4 hours.

• East Africa: availability is very limited.

Formulations. Inhalation solution 10 micrograms/mL and 20 micrograms/mL in ampoules; injection concentrate.

Administration. Use the dedicated nebuliser device only. Avoid contact with skin and eyes. Rinse the mouth afterwards. Ventilate the room because exhaled drug can reach others.

Baseline. Blood pressure, right heart catheter results, functional class, 6 minute walk distance, NT-proBNP, bleeding history.

Monitoring. Blood pressure and heart rate at titration. Cough and bronchospasm. Clinical review every 3 to 6 months.

Stop and reduce rules. Reduce the dose or lengthen the interval for symptomatic hypotension. Stop for severe bronchospasm or bleeding. Do not stop suddenly. Therapeutic drug monitoring is not used.

Referral and escalation. Manage in a PAH centre. Refer for worsening class, syncope or right heart failure.