Drug information of Iloprost

Mechanism of effect

Iloprost is a second generation structural analog of prostacyclin (PGI) with about ten-fold greater potency than the first generation stable analogs, such as carbaprostacyclin. Iloprost binds with equal affinity to human prostacyclin (Prostanoid IP) and prostaglandin EP1 receptors.

Iloprost constricts the ilium and fundus circular smooth muscle as strongly as prostaglandin E2 (PGE2) itself. Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets. In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time.

All of these properties help to antagonize the pathological changes that take place in the small pulmonary arteries of patients with pulmonary hypertension.

Pharmacodynamic

Iloprost is a synthetic analogue of prostacyclin PGI2. Iloprost dilates systemic and pulmonary arterial vascular beds. It also affects platelet aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer.

Pharmacokinetics

Absorption : Rapidly absorbed with bioavailability of 63% 

Volume of distribution : 0.7 to 0.8 L/kg

 Protein binding : 60%

Metabolism : Primarily hepatic. Iloprost is metabolized principally via beta-oxidation of the carboxyl side chain.

Route of elimination : Not Available

Half life : 20-30 minutes

Clearance : 20 mL/min/kg

Dosage

Usual Adult Dose for Pulmonary Hypertension

Initial dose: 2.5 mcg inhaled orally once; if tolerated, increase to 5 mcg and maintain this dose
Maintenance dose: 2.5 or 5 mcg inhaled orally 6 to 9 times per day, no more than once every 2 hours while awake, based on individual need and tolerability
Maximum dose: 45 mcg/day (5 mcg/dose 9 times per day) 

Treatment of patients with severe peripheral arterial occlusive disease (eg. (Buerger's disease, Raynaud's phenomenon)

Iloprost is administered after dilution as an intravenous infusion over 6 hours daily via a peripheral vein or a central venous catheter. For each daily infusion, prepare a 200nanogram/ml solution by adding the contents of one 50microgram of iloprost to a 250ml bag of sodium chloride 0.9%

During the first 2 - 3 days, the individually tolerated dose is established. For this purpose, treatment should be started at an infusion rate to deliver 0.5 ng/kg/min. for 30 minutes. The dose should then be increased at intervals of about 30 minutes in steps of 0.5 ng/kg/min. up to 2.0 ng/kg/min.

From day 4 administer the infusion should be started and continued at the optimal infusion rate determined on days 1-3
Doses should be halved in patients with liver cirrhosis or those undergoing haemodialysis

Patient’s weight (kg): 50

Initial rate (0.5nanograms /kg/min) : 7.5 ml/hr

Step 2 (1nanogram /kg/min) : 15 ml/hr

Step 3 (1.5nanograms /kg/min) : 22.5 ml/hr

 Maximum rate (2nanograms /kg/min) : 30 ml/hr

Side effects

Insomnia , Headache , nausea , vomiting , flushing , palpitations , Hypersensitivity , pneumonia , Back pain , Syncope , bronchial spasm , impairment of renal function

Interactions

Levodopa/carbidopa , Minoxidil , Hydralazine , Captopril , Dabigatran , Tositumomab , Ibritumomab tiuxetan , Betrixaban , Ramucirumab , Treprostinil , Dasatinib

Alerts

• Do NOT use iloprost if:
• you are allergic to any ingredient in iloprost
• you have certain lung problems (eg, chronic respiratory acidosis)

Contact your doctor or health care provider right away if any of these apply to you.

• Use cautiously if you have below conditions:

Pregnancy, Lactation, Hypersensitivity to iloprost , Conditions where the effects of iloprost on platelets might increase the risk of haemorrhage, Severe coronary heart disease or unstable angina, Myocardial infarction within the last six months, Acute or chronic congestive cardiac failure (NYHA type II to IV), Arrhythmias of prognostic significance, Suspected pulmonary congestion

• Iloprost elimination is reduced in patients with hepatic dysfunction and in patients with renal failure requiring dialysis.
• Iloprost should not be initiated in patients with systolic arterial hypotension less than 85 mmHg.
• In patients with PHT with low systemic blood pressure or at high risk of cardiac output failure, careful initiation of the therapy, under close hemodynamic monitoring, must be
• Iloprost should not be used as the first treatment option in thromboembolic pulmonary hypertension if surgery is feasible.
• Monitor blood pressure, heart rate and oxygen saturations at the start of the infusion and at 30 minute intervals during the infusion.

Points of recommendation

-Follow the manufacturer instructions for proper administration techniques, including dosing frequency, ampule dispensing, and I-neb(R) AAD(R) System operation and equipment cleaning.
-Stand up slowly as a fall in blood pressure may occur, causing dizziness and possible fainting.
-Consult your physician if fainting gets worse.

Pregnancy level

C

Related drugs

Alprostadil , Epoprostenol