Iloprost in Adults with Peripheral Vascular Disease or Raynaud’s Phenomenon

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Iloprost is a synthetic prostacyclin analogue used in the treatment of critical limb ischaemia in patients at risk of amputation where surgical revascularisation or angioplasty is not indicated or has failed, or for severe Raynaud’s phenomenon.  It improves circulation by dilating systemic vascular beds, inhibiting platelet aggregation and exerting an anti-inflammatory effect on injured tissue. For both indications it is usually given as an infusion for 6 hours a day for five days. The decision to prescribe iloprost should be led by a consultant rheumatologist or vascular surgeon.

It is worth noting that unlike other medicines where the dose is fixed and given over a set period of time, the licensing for iloprost means that the duration of infusion is fixed, 6 hours, but the total dose will vary between patients depending on characteristics such as weight and tolerance. In some circumstances treatment may be extended beyond 6 hours in 24 hours at the discretion of the prescribing consultant. This is however on off label use and should be considered on a case by case basis.  

Additional prescribing and monitoring information is available on the injectable medicines guide, Medusa (password access) and manufacturer's summary of product characteristics.

Side effects and cautions

The most commonly observed adverse events (≥ 10%) are headache, flushing, nausea, vomiting and hyperhidrosis. These undesirable effects are likely to occur during the dose titration and can be used to identify the best tolerable dose for the individual patient as they generally resolve following dose reduction.

Management of adverse reactions

  • hypotension, tachycardia, vagal reaction with bradycardia: stop infusion and consider IV fluids, can be restarted at half the previous rate
  • facial flushing, headache, nausea/vomiting, abdominal cramps or diarrhoea: reduce rate by 0.5nanogram/kg/min if intolerable, antiemetics and paracetamol can be prescribed
  • fever, apathy, limb pain: treat conservatively, paracetamol and reassurance

Iloprost may increase the anti-hypertensive activity of β- blockers, calcium antagonists, vasodilators and ACE inhibitors. In case of significant hypotension, this can be corrected by dose reduction of iloprost. Alternatively, while there is little evidence to support withholding these drugs prior to the start of the infusion, in practice this is something that may be done on a cases by case basis to improve tolerability.

Because iloprost inhibits platelet aggregation, concomitant use of anticoagulant or antiplatelets may increase the risk of bleeding. The possible increase in haemorrhagic risk should be taken into account by maintaining close clinical monitoring. Should clinically significant bleeding occur, iloprost administration should be stopped.

Indication and dosing

Treatment of severe chronic ischemia of the lower limbs

  • The recommended dosage varies between 0.5 to 2 nanogram/kg/min for an infusion of 6 hours per day depending on the patient's tolerance. Treatment can continue for up to 28 days using the tolerated dose determined during the first two or three days of treatment. In practice the duration of treatment is usually 5 days but as noted above this may be extended. The efficacy and safety of repeated courses has not been established for this indication.

Treatment of Severe Raynaud's Phenomenon

  • The recommended dosage varies between 1.5 to 2 nanogram/kg/min depending on the patient's tolerance. The duration of the infusion will be 6hr/per day for 5 consecutive days, using the maximum tolerated dose determined during the first days of treatment. Repeat cycles should preferably take place at intervals of 6 to 12 weeks (and never less than 4 weeks)
Method of administration

Iloprost is supplied from pharmacy as a 50micrograms in 0.5mL ampoule, while other strengths are available, these are not stocked. Prior to administration the ampoule should be diluted in 250mL of sodium chloride 0.9% or glucose 5% to give a final concentration of 200nanograms in 1mL (0.2micrograms in 1mL) and given via a volumetric infusion pump.

Treatment should be started at an infusion rate of 0.5 nanogram/kg/min for 30 minutes. The dose should then be increased at intervals of 30 minutes by 0.5 nanogram/kg/min to a maximum of 2.0 nanogram/kg/min. The exact infusion rate should be calculated on the basis of body weight to reach an infusion within the range of 0.5 to 2.0 nanogram/kg/min.

Special populations

For patients on renal dialysis or those severe hepatic impairment iloprost plasma levels may be increased due to impaired elimination. In these patients the rate should be started at 0.25 nanogram/kg/min for 30 minutes and the dose increased at intervals of 30 minutes by 0.25 nanogram/kg/min to a maximum of 1 nanogram/kg/min

The formula below can be used to calculate the infusion rate.

Alternatively, table 1 below details weight banded infusion rates based on patient's actual body weight.


Iloprost should be prescribed and administered on the fluid chart and documented ‘as per fluid chart’ on the regular medications section of the prescription chart.

References

Summary of Product Characteristics. Iloprost 100 micrograms/ml concentrate for solution for infusion. Colonis Pharma Ltd. Updated 16/02/21. Available from: https://www.medicines.org.uk/emc/product/10034/smpc

Injectable medicines guide. Iloprost Monograph. Updated 09/09/2020. Available From: https://nww.injguide.nhs.uk

Editorial Information

Last reviewed: 30 April 2021

Next review: 30 April 2024

Approved By: TAM Subgroup of ADTC

Reviewer Name(s): Specialist Clinical Pharmacist - Surgery

Document Id: TAM473