Epoprostenol

When NSAIDs or other drugs affecting platelet aggregation are used concomitantly, there is the potential for epoprostenol to increase the risk of bleeding.

The vasodilator effects of epoprostenol may augment or be augmented by concomitant use of other vasodilators.

Patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with epoprostenol, which – although transient – may be clinically significant in patients prone to digoxin toxicity.

As reported with other prostaglandin analogues, epoprostenol may reduce the thrombolytic efficacy of tissue plasminogen activator (t-PA) by increasing hepatic clearance of t-PA.

Extreme caution is advised in patients with coronary artery disease.

There is limited data from the use of epoprostenol in pregnant women. Animal studies did not indicate harmful effects with respect to reproductive toxicity. Given the absence of alternative medicines, epoprostenol can be used in women who choose to continue their pregnancy, despite the known risk of pulmonary arterial hypertension during pregnancy.

It is unknown if epoprostenol or its metabolites are excreted in human milk. A risk to the breastfeeding child cannot be excluded. Breastfeeding should be discontinued during treatment with epoprostenol.

Fertility

There are no data on the effects of epoprostenol on fertility in humans. Reproductive studies in animals have shown no effects on fertility.

Pulmonary arterial hypertension and its therapeutic management may affect the ability to drive and operate machinery.

There are no data regarding the effect of epoprostenol used in renal dialysis on the ability to drive or operate machinery.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as follows: very common ≥1/10 (≥10%); common ≥1/100 and <1/10 (≥1% and <10%); uncommon ≥1/1000 and <1/100 (≥0.1% and <1%); rare ≥1/10,000 and <1/1000 (≥0.01% and <0.1%); very rare <1/10,000 (<0.01%) and not known (cannot be estimated from the available data).

Infections and Infestations

Common: Sepsis, septicaemia (mostly related to delivery system for epoprostenol)¹

Blood and Lymphatic System Disorders

Common: Decreased platelet count, bleeding at various sites (e.g. pulmonary, gastrointestinal, epistaxis, intracranial, post-procedural, retroperitoneal)

Unknown: Splenomegaly, Hypersplenism

Endocrine Disorders

Very rare: Hyperthyroidism

Psychiatric Disorders

Common: Anxiety, nervousness

Very rare: Agitation

Nervous System Disorders

Very common: Headache

Cardiac Disorders

Common: Tachycardia², bradycardia³

Not known: High output cardiac failure

Vascular Disorders

Very common: Facial flushing (seen even in the anaesthetised patient)

Common: Hypotension

Very rare: Pallor

Not known: Ascites

Respiratory, Thoracic and Mediastinal Disorders

Unknown: Pulmonary oedema

Gastrointestinal Disorders

Very common: Nausea, vomiting, diarrhoea

Common: Abdominal colic, sometimes reported as abdominal discomfort

Uncommon: Dry mouth

Skin and Subcutaneous Tissue Disorders

Common: Rash

Uncommon: Sweating

Musculoskeletal and Connective Tissue Disorders

Very common: Jaw pain

Common: Arthralgia

General Disorders and Administration Site Conditions

Very common: Pain (unspecified)

Common: Pain at the injection site*, chest pain

Rare: Local infection*

Very rare: Erythema over the infusion site*, occlusion of the long i.v. catheter*, lassitude, chest tightness

Investigations

Unknown: Blood glucose increased

* Associated with the delivery system for epoprostenol
¹ Catheter-related infections caused by organisms not always considered pathogenic (including micrococcus) have been reported.
² Tachycardia has been reported as a response to epoprostenol at doses of 5 ng/kg/min and below.
³ Bradycardia, sometimes accompanied by orthostatic hypotension, has occurred in healthy volunteers at doses of epoprostenol greater than 5 ng/kg/min. Bradycardia associated with a considerable fall in systolic and diastolic blood pressure has followed i.v. administration of a dose of epoprostenol equivalent to 30 ng/kg/min in healthy conscious volunteers.