Chemical formula: C₂₂H₃₂O₄ Molecular mass: 360.494 g/mol PubChem compound: 5311181
Iloprost interacts in the following cases:
Iloprost elimination is reduced in patients with hepatic dysfunction.
To avoid undesired accumulation over the day, special caution has to be exercised with these patients during initial dose titration. Initially, doses of 2.5 microgram iloprost should be administered using iloprost 10 microgram/ml with dosing intervals of 3-4 hours (corresponds to administration of max. 6 times per day). Thereafter, dosing intervals may be shortened cautiously based on individual tolerability. If a dose up to 5 microgram iloprost is indicated, again dosing intervals of 3-4 hours should be chosen initially and shortened according to individual tolerability. An accumulation of iloprost following treatment over several days is not likely due to the overnight break in administration of the medicinal product.
Patients with a creatinine clearance of ≤30 ml/min were not investigated in the clinical trials. Data with intravenously administered iloprost indicated that the elimination is reduced in patients with renal failure requiring dialysis. Therefore, the same dosing recommendations as in patients with hepatic impairment are to be applied.
Since iloprost inhibits platelet function its use with the following substances may enhance iloprost-mediated platelet inhibition, thereby increasing the risk of bleeding:
A careful monitoring of the patients taking anticoagulants or other inhibitors of platelet aggregation according to common medical practice is recommended.
Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk of hypotension. Caution is recommended in case of co-administration of iloprost with other antihypertensive or vasodilatating agents as dose adjustment might be required.
Women with pulmonary hypertension (PH) should avoid pregnancy as it may lead to life-threatening exacerbation of the disease. Iloprost concentrate for solution for infusion is contraindicated during pregnancy.
Studies in animals have shown embryotoxicity in rats but not in rabbits and monkey.
There is a limited amount of data from the use of iloprost in pregnant women. If a pregnancy occurs, taking into account the potential maternal benefit, the use of iloprost during pregnancy may be considered, only following careful benefit-risk evaluation, in those women who choose to continue their pregnancy, despite the known risks of pulmonary hypertension during pregnancy.
It is not known whether iloprost/metabolites are excreted in human breast milk. Very low levels of iloprost into milk were observed in rats. A potential risk to the breast-feeding child cannot be excluded and it is preferable to avoid breast-feeding during iloprost therapy.
Iloprost 100 micrograms/ml concentrate for solution for infusion therapy is contraindicated during breast-feeding. It is unknown whether iloprost is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from iloprost taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Women of childbearing potential should use effective contraceptive measures during treatment with iloprost.
Animal studies have not shown harmful effect of iloprost on fertility.
Iloprost has major influence on the ability to drive and use machines for patients experiencing hypotensive symptoms such as dizziness. Care should be exercised during initiation of therapy until any effects on the individual have been determined.
In addition to local effects resulting from administration of iloprost by inhalation such as cough, adverse reactions with iloprost are related to the pharmacological properties of prostacyclins.
The most frequently observed adverse reactions (≥20%) in clinical trials include vasodilatation (including hypotension), headache and cough. The most serious adverse reactions were hypotension, bleeding events, and bronchospasm.
The adverse reactions reported below are based on pooled clinical trial data from phase II and III clinical trials involving 131 patients taking the medicinal product and on data from post-marketing surveillance. The frequencies of adverse reactions are defined as very common (≥1/10) and common (≥1/100 to <1/10). The adverse reactions identified only during post-marketing surveillance, and for which a frequency could not be estimated from clinical trial data, are listed under “Frequency not known”.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Very common: Bleeding events*§
Not known: Thrombocytopenia
Not known: Hypersensitivity
Very common: Headache
Common: Dizziness
Common: Tachycardia, Palpitations
Very common: Vasodilatation, Flushing
Common: Syncope§, Hypotension*
Very common: Chest discomfort/chest pain, Cough
Common: Dyspnoea, Pharyngolaryngeal pain, Throat irritation
Not known: Bronchospasm*/Wheezing
Very common: Nausea
Common: Diarrhoea, Vomiting, Mouth and tongue irritation including pain
Not known: Dysgeusia
Common: Rash
Very common: Pain in jaw/trismus
Very common: Peripheral oedema§
* Life-threatening and/or fatal cases have been reported.
§ see section "Description of selected adverse reactions"
Bleeding events (mostly epistaxis and haemoptysis) were very common as expected in this patient population with a high proportion of patients taking anticoagulant co-medication. The risk of bleeding may be increased in patients when potential inhibitors of platelet aggregation or anticoagulants are given concomitantly. Fatal cases included cerebral and intracranial haemorrhage.
Syncope is a common symptom of the disease itself, but can also occur under therapy. The increased occurrence of syncope can be related to the deterioration of the disease or insufficient effectiveness of the product.
In clinical trials peripheral oedema was reported in 12.2% of patients on iloprost and 16.2% of patients on placebo. Peripheral oedema is a very common symptom of the disease itself, but can also occur under therapy. The occurrence of peripheral oedema can be related to the deterioration of the disease or insufficient effectiveness of the product.
The overall safety profile of iloprost is based on data from post-marketing surveillance as well as on pooled clinical trial data. The raw incidence was 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 advanced stages III and IV, and patients with thromboangiitis obliterans (TAO); for details see the following list.
The most common observed adverse events (≥10%) in patients receiving iloprost in clinical trials are headache, flushing, nausea, vomiting and hyperhidrosis. These undesirable effects are likely to occur during the dose titration at the start of treatment to identify the best tolerable dose for the individual patient. Usually these undesirable effects resolve with dose reduction.
Overall, the most severe undesirable effects (life-threatening or fatal) in patients receiving iloprost are cerebrovascular stroke, 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 linear erythema above the infusion vein.
Adverse reactions observed after use of iloprost 100 micrograms/1 ml are listed below. They are classified by system organ class (MedDRA version 19.0). The most appropriate MedDRA term has been selected to describe a certain reaction and its synonyms and associated conditions.
Adverse reactions from clinical studies are classified by their frequency.
The following categories are used for stating the frequency of adverse reactions: 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), Not known (cannot be estimated from the available data).
Adverse reactions reported during clinical studies or observed in post-marketing experience in patients treated with iloprost 100micrograms/ml:
Uncommon: Thrombocytopenia
Uncommon: Hypersensitivity
Common: Decreased appetite
Common: Bradypsychia, Confusional state
Uncommon: Anxiety, Depression, Hallucination
Very common: Headache
Common: Dizziness/Vertigo, Paraesthesia/Palpitations/Hyperaesthesia/Burning sensation, Restlessness/drowsiness
Uncommon: Convulsion*, Syncope, Tremor, Migraine
Uncommon: Vision blurred, Eye irritation, Eye pain
Common: Tachycardia*, Bradycardia, Angina pectoris*
Uncommon: Myocardial infarction*, Cardiac failure*, Arrhythmia/Extrasystoles*,
Very common: Flushing
Common: Hypotension*, Blood pressure increased
Uncommon: Cerebrovascular event*/Cerebral ischaemia, pulmonary embolism*, Deep vein thrombosis
Common: Dyspnoea*
Uncommon: Asthma*, Pulmonary oedema*
Rare: Cough
Very common: Nausea, Vomiting
Common: Diarrhoea, Abdominal discomfort/Abdominal pain
Uncommon: Diarrhoea haemorrhagic, Rectal haemorrhage, Dyspepsia, Rectal tenesmus, Constipation, Dysphagia, Dry mouth/Dysgeusia
Rare: Proctitis
Uncommon: Hepatic impairment
Very common: Hyperhidrosis
Uncommon: Pruritus
Common: Pain in jaw/Trismus, Myalgia/Arthralgia
Uncommon: Tetany/Muscle spasms
Uncommon: Kidney pain, Dysuria
Common: Pain, Pyrexia/Body temperature increased, Feeling hot, Asthenia, Chills, Thirst, Infusion site reactions (infusion site erythema, infusion site pain, infusion site phlebitis)
* life threatening and/or fatal cases have been reported
Iloprost may cause angina pectoris, especially in patients with coronary artery disease.
The risk of bleeding is increased in patients when inhibitors of platelet aggregation, heparin or coumarin-type anticoagulants are given concomitantly.
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