ILOMEDIN Solution for infusion Ref.[28118] Active ingredients: Iloprost

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 (see Dose and method of administration and Pharmacokinetic properties).

In patients with low blood pressure care should be taken to avoid further hypotension and patients with significant heart disease should be closely monitored. ILOMEDIN 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 haemodynamic monitoring, must be taken. This is necessary to avoid further hypotension or other undesirable effects such as a decrease in mean systemic arterial pressure and vascular resistance leading to a worsening of cardiac output.

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.

Patients with acute pulmonary infections, chronic obstructive pulmonary disease, and severe asthma should be carefully monitored. ILOMEDIN should not be used as the first treatment option in thromboembolic pulmonary hypertension if surgery is feasible.

In the long-term administration of intravenous iloprost for PHT, particularly in a community setting, care should be taken to avoid any infection or sepsis arising from the procedures necessary for the administration of ILOMEDIN.

Currently only sporadic reports of use in children and adolescents are available. ILOMEDIN should be used only after dilution. Because of the possibility of interactions, no other medicine should be added to the ready-to-use infusion solution.

The paravascular infusion of undiluted ILOMEDIN 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.

Iloprost may increase the antihypertensive activity of β-receptor blockers, calcium antagonists, vasodilators and ACE inhibitors. Should significant hypotension occur this can be corrected by dose reduction of iloprost.

Because iloprost inhibits platelet function, its use with anticoagulants (such as heparin coumarintype anticoagulants), or other inhibitors of platelet aggregation (such as acetylsalicylic acid, nonsteroidal anti-inflammatory medicines, phosphodiesterase inhibitors and nitro vasodilators e.g. molsidomine) may increase the risk of bleeding. If this occurs, iloprost administration should be stopped.

Oral premedication with acetylsalicylic acid up to 300 mg per day over a period of 8 days had no impact on the pharmacokinetics of iloprost. In an animal study, it was found that iloprost may result in a reduction in t-PA steady-state plasma concentration. The results of human studies show that iloprost infusions do not affect the pharmacokinetics of multiple oral doses of digoxin in patients and iloprost has no impact on the pharmacokinetics of co-administered t-PA.

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 known.

Although, clinical studies have not been conducted, in vitro studies investigating the inhibitory potential of iloprost on the activity of cytochrome P450 enzymes revealed that no relevant inhibition of medicine metabolism via these enzymes by iloprost have to be expected.

ILOMEDIN must not be administered to pregnant or lactating women.

Use in pregnancy

There are no adequate data from the use of iloprost in pregnant women. Preclinical studies have shown evidence of foetotoxicity in rats, but not rabbits and monkeys (see Preclinical safety data).

As the potential risk of the therapeutic use of iloprost during pregnancy is unknown, women of childbearing potential should use effective contraceptive measures during treatment.

Use in lactation

It is not known whether iloprost enters human breast milk. As extremely low levels of iloprost pass into the milk of rats, iloprost should not be administered to nursing women.

It is unlikely that ILOMEDIN will have any deleterious effects (e.g. sedation), but care should be exercised during initiation of therapy until any effects on the individual have been determined. In patients experiencing hypotensive symptoms such as dizziness, ability to drive or operate machinery may be seriously affected.

The most frequently observed adverse drug reactions (≥10%) in patient 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, dyspnoea and pulmonary oedema.

Another group of side effects is related to the local infusion site reactions. For example, infusion site redness and infusion site pain may occur or a cutaneous vasodilation may give rise to a streaky erythema above the infusion vein.

The adverse drug reactions observed with ILOMEDIN are represented in the table below. They are classified according to System Organ Class (MedDRA version 14.1). 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 below: Very common: ≥1/10, Common: ≥1/100 to <1/10, Uncommon: ≥1/1,000 to <1/100, Rare: ≥1/10,000 to <1/1,000, Very rare: <1/10,000.

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 1.

Table 1. Adverse drug reactions reported in clinical trials or during post-marketing surveillance in patients treated with ILOMEDIN:

^* life threatening and/or fatal cases have been reported

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/

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.

No data available for other than those medicinal products described under 6.6 Special precautions for disposal and other handling.