Ilomedin 20

Iloprost trometamol.

1 ml Ilomedin 20 contains 0.027 mg iloprost trometamol (equivalent to 0.020 mg iloprost) in aqueous solution.

Ilomedin 20 promotes the healing of ulcerations secondary to ischemia and alleviates the pain in severe, chronic disturbances of arterial circulation.

Treatment of advanced thromboangiitis obliterans (Buerger's disease) with critical limb ischemia in cases where revascularization is not indicated.
Treatment of patients with severe peripheral arterial occlusive disease (PAOD), particularly those at risk of amputation and in whom surgery or angioplasty is not possible.
Treatment of patients with severe disabling Raynaud's phenomenon unresponsive to other therapies.

Ilomedin 20 should be used only under strict monitoring in hospitals or outpatient clinics with adequate facilities.
Pregnancy must be excluded before the start of treatment in women.
Ilomedin 20 is administered after dilution as an intravenous infusion over 6 hours daily via a peripheral vein or a central venous catheter. The dose is adjusted according to individual tolerability within the range of 0.5 to 2.0 ng iloprost/kg body weight/min.
The infusion solution should be made up freshly each day to ensure sterility.
During the first 2 to 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. The exact infusion rate should be calculated on basis of the body weight to effect an infusion within the range of 0.5 to 2.0 ng/kg/min. (see Tables 1 and 2 as follows for use of infusion pump or for use with syringe driver).
Depending on the occurrence of side effects such as headache and nausea or an undesired decrease in blood pressure, the infusion rate should be reduced until the tolerable dose is found. If the side effects are severe, the infusion should be interrupted. For the rest of the treatment period, therapy should be continued with the dose found to be tolerated in the first 2 to 3 days.
The blood pressure and heart rate must be measured at the start of the infusion and after every increase in the dose.
Infusion rates [ml/hour] for different doses for use of infusion pump: In general, the ready-for-use infusion solution is infused intravenously by means of an infusion pump (e.g. Infusomat). For this purpose, the contents of a 2.5-ml ampul (i.e. 50 μg) of Ilomedin 20 are diluted with sterile physiological saline solution or a 5% glucose solution to the final volume for infusion of 250 ml, and the contents of a 1-mL ampul (i.e. 20 μg) of Ilomedin 20 are diluted with sterile physiological saline solution or a 5% glucose solution to the final volume for infusion of 100 ml. The contents of the ampul and the diluent should be mixed thoroughly. In the case of an Ilomedin 20 concentration of 0.2 μg/ml, the required infusion rate should be determined according to the previously described scheme to effect a dose within the range of 0.5 to 2.0 ng/kg/min.
(Please interpolate to match the patient's actual body weight, then set the infusion rate to the target dose in ng/kg/min.) (See Table 1.)

Click on icon to see table/diagram/image

Infusion rates [ml/hour] for different doses for use of syringe driver: A syringe driver with a 50-ml injection syringe (e.g. the Perfusor) may also be used. In this case, the contents of one 2.5-ml ampul (i.e. 50 μg) of Ilomedin 20 are diluted with sterile physiological saline solution or 5% glucose solution, to reach a final volume of 25 ml, and the contents of one 1-ml ampul (i.e. 20 μg) of Ilomedin 20 are diluted with sterile physiological saline solution or 5% glucose solution to reach a final volume of 10 ml. In the case of an Ilomedin 20 concentration of 2 μg/ml, the required infusion rate should be determined according to the previously described scheme to effect a dose within the range of 0.5 to 2.0 ng/kg/min.
(Please interpolate to match the patient's actual body weight, then set the infusion rate to the target dose in ng/kg/min.) (See Table 2.)

Click on icon to see table/diagram/image

The duration of treatment is up to 4 weeks. Shorter treatment periods (3 to 5 days) are often sufficient in Raynaud's phenomenon to achieve improvement over several weeks.
It should be borne in mind that iloprost elimination is reduced in patients with renal failure requiring dialysis and in patients with liver cirrhosis. In these patients a dose reduction (e.g. half the recommended dose) is necessary.
Continuous infusion over several days is not recommended because of the possible development of tachyphylaxis of platelet effects and the possibility of rebound platelet hyperaggregability at the end of treatment, although no clinical complications associated with these phenomena have been reported.

Symptoms: Hypotensive reaction might be anticipated as well as headache, flushing, nausea, vomiting and diarrhea. An increase of blood pressure, bradycardia or tachycardia and limb or back pain might be possible.
Therapy: A specific antidote is not known.
Interruption of iloprost administration, monitoring and symptomatic measures are recommended.

Pregnancy, lactation, hypersensitivity to iloprost or to any of the other ingredients.
Conditions where the effects of Ilomedin 20 on platelets might increase the risk of hemorrhage (e.g. active peptic ulcers, trauma, intracranial hemorrhage).
Severe coronary heart disease or unstable angina; myocardial infarction within the last six months; acute or chronic congestive heart failure (NYHA II-IV); severe arrhythmias; suspected pulmonary congestion.

Surgery should not be delayed in patients requiring urgent amputation (e.g. in infected gangrene).
Patients should be strongly advised to stop smoking.
Iloprost elimination is reduced in patients with hepatic dysfunction and in patients with renal failure requiring dialysis.
In patients with low blood pressure care should be taken to avoid further hypotension and patients with significant heart disease should be closely monitored.
The possibility of orthostatic hypotension should be borne in mind in patients getting up from the lying to an upright position after the end of administration.
For patients with a cerebrovascular event [e.g. transient ischemic attack, stroke] within the last 3 months a careful benefit-risk evaluation should be undertaken.

Currently, only sporadic reports of use in children and adolescents are available.
The paravascular infusion of undiluted Ilomedin 20 can lead to local changes at the injection site.
Oral ingestion and contact with mucous membranes must be avoided. On contact with the skin, iloprost may provoke long-lasting but painless erythema. Suitable precautions should therefore be taken to avoid iloprost contact with the skin. In the event of such contact, the affected area should be washed immediately with copious amounts of water or saline.

Summary of the safety profile: The overall safety profile of Ilomedin is based on data from post-marketing surveillance and on pooled clinical trial data. The crude incidences were based on the cumulative database of 3325 patients having received iloprost either in controlled or uncontrolled clinical trials or in a compassionate use program from generally elderly and multimorbid patients with peripheral arterial occlusive disease (PAOD) in its advanced stages III and IV and patients with thromboangiitis obliterans (TAO), for details see Table 3.
The most frequently observed adverse drug reactions (≥10%) in patients receiving iloprost in clinical trials are headache, flushing, nausea, vomiting and hyperhidrosis. These are likely to occur while the dose is titrated at the start of treatment to identify the best tolerable dose for the individual patient. However, all these side effects usually disappear quickly with dose reduction.
Overall, the most serious adverse drug reactions in patients receiving iloprost are cerebrovascular accident, myocardial infarction, pulmonary embolism, cardiac failure, convulsion, hypotension, tachycardia, asthma, angina pectoris, dyspnea and pulmonary edema.
Another group of side effects is related to local infusion site reactions. For example, infusion site redness and infusion site pain may occur or a cutaneous vasodilation may give rise to streaky erythema above the infusion vein.
Tabulated list of adverse reactions: The adverse drug reactions observed with Ilomedin are represented in Table 3 as follows. They are classified according to System Organ Class. The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
Adverse drug reactions from clinical trials are classified according to their frequencies. Frequency groupings are defined according to the following convention: very common ≥1/10, common ≥1/100 to <1/10, uncommon ≥1/1,000 to <1/100 and rare ≥1/10,000 to <1/1,000. (See Table 3.)

Click on icon to see table/diagram/image

Iloprost may provoke angina pectoris, especially in patients with coronary artery disease. The risk of bleeding is increased in patients when inhibitors of platelet aggregation, heparin or anticoagulants of the coumarin-type are given concomitantly.

In pharmacological experiments, iloprost has shown an additive effect on the antihypertensive activity of β-receptor blockers, calcium antagonists and vasodilators, and a potentiating effect on the antihypertensive activity of ACE inhibitors. These findings could not be confirmed in human volunteers. Should significant hypotension occur this can be corrected by reducing the dose of iloprost.
In animal experiments, the vasodilatory effect of iloprost is attenuated when the animals are pretreated with glucocorticoids, while the inhibitory effect on platelet aggregation remains unaffected. The significance of this finding for use in man is not yet known.
Because iloprost inhibits platelet function, its use with heparin or coumarin-type anticoagulants, which affect other hemostatic mechanisms, theoretically may increase the risk of bleeding. If this occurs, iloprost infusion should be stopped.
Iloprost has an additive or superadditive effect on platelet function with other inhibitors of platelet aggregation (acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs, phosphodiesterase inhibitors and nitrovasodilators (e.g. molsidomine).

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AC11 - iloprost ; Belongs to the class of platelet aggregation inhibitors excluding heparin. Used in the treatment of thrombosis.

P₁S₁S₃