Flolan Side Effects

Generic name: epoprostenol

Note: This document contains side effect information about epoprostenol. Some of the dosage forms listed on this page may not apply to the brand name Flolan.

Some side effects of Flolan may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to epoprostenol: intravenous powder for injection

Get emergency medical help if you have any of these signs of an allergic reaction while taking epoprostenol (the active ingredient contained in Flolan) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• fever, flu symptoms, mouth and throat ulcers, rapid heart rate, rapid and shallow breathing, fainting;

• chest pain, trouble breathing;

• fast, slow, or uneven heart rate;

• pale skin, easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• blood in your urine or stools;

• coughing up blood;

• feeling like you might pass out; or

• numbness or increased sensitivity anywhere in your body.

Less serious side effects of epoprostenol may include:

• flushing (warmth, redness, or tingly feeling);

• nausea, vomiting, diarrhea, stomach pain;

• headache or jaw pain;

• joint or muscle pain;

• dizziness, sweating; or

• feeling anxious, nervous, or agitated.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to epoprostenol: intravenous powder for injection

General

Adverse effects due to epoprostenol (the active ingredient contained in Flolan) are often difficult to distinguish from the symptoms of primary pulmonary hypertension. Adverse effects due to the disease state have included dyspnea, fatigue, chest pain, right ventricular failure and pallor. Side effects more common due to the drug have included headache, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms and anxiety.

Cardiovascular

Bugiardini and colleagues reported that epoprostenol (the active ingredient contained in Flolan) at therapeutic doses has been shown to induced myocardial ischemia (angina, ST segment depression, reduced lactate consumption) in patients with advanced coronary artery disease. The mechanism may be due to a maldistribution of blood flow. Counteraction of ischemia was achieved with aminophylline.

Proarrhythmic and antiarrhythmic effects have been rarely reported. In one study, epoprostenol infusion increased the induction of atrial and ventricular arrhythmias and decreased atrial and AV nodal conduction times possibly related to an increase in adrenergic tone.

Davenport and colleagues reported on 8 patients receiving direct femoral infusions of epoprostenol (5 ng/kg/min) for 30 minutes prior to hemodialysis to prevent extracorporeal clotting. All patients had fulminant hepatic failure and acute renal failure due to acetaminophen self-poisoning. Mean arterial pressure, cerebral perfusion pressure and arterial oxygen pressure all decreased. Intracranial pressure increased while cardiac output did not change. Four of these patients subsequently died due to cerebral edema. The authors suggest to administer epoprostenol only via the infusion port on the extracorporeal circuit, and not directly, in patients with hepatic and renal failure requiring hemodialysis to help prevent changes in cerebral perfusion pressure and oxygen delivery.

Zusman and colleagues reported that epoprostenol at 8 ng/kg/min, compared to 2 ng/kg/min or 4 ng/kg/min lead to increased adverse effects in patients with chronic renal failure undergoing hemodialysis anticoagulation. Hypotension was the primary adverse cardiovascular event requiring discontinuation of the higher dosage. Hemodynamic changes included a decreased blood pressure and increased heart rate. Patients with chronic renal failure may exhibit increased hemodynamic sensitivity, possibly due to higher basal plasma prostaglandin levels.

Cardiovascular side effects have included flushing (58% of patients) and hypotension (16%). These two side effects are commonly dose-limiting in the acute dose-ranging phase of epoprostenol administration. These effects have usually occurred due to potent vasodilation. Chest pain (11%), bradycardia (5%) and tachycardia (1%) have also been reported during acute dosing. Adverse cardiovascular events occurring during chronic infusions include tachycardia (35%) and flushing (42%). Fatal cerebral edema has been reported.

Nervous system

In dose-ranging studies headache was the dose-limiting side effect most frequently reported.

Nervous system side effects have included reports of headache (due to vasodilation) in approximately 50% of patients during acute dose ranging and in 83% of patients during chronic dosing. Anxiety, nervousness, and agitation have been reported in 11% of patients and dizziness in 8% of patients during acute phase dose ranging. Anxiety, nervousness and tremor have been reported in 21% of patients during the chronic phase.

Gastrointestinal

Gastrointestinal side effects have included reports of nausea and vomiting in 32% of patients during the acute dose ranging phase and in 67% of patients during chronic dosing. Dyspepsia and abdominal pain have occurred in less than 5% of patients during acute dosing. Diarrhea has been reported in 67% of patients during the chronic phase.

Zusman and colleagues reported that epoprostenol at 8 ng/kg/min, compared to 2 ng/kg/min or 4 ng/kg/min lead to increased adverse effects in patients with chronic renal failure undergoing hemodialysis anticoagulation. Nausea and vomiting were the 2 primary adverse gastrointestinal events requiring discontinuation of the higher dosage.

Musculoskeletal

Musculoskeletal side effects have included rare reports of back pain and musculoskeletal pain during acute dosing. In the chronic phase, jaw pain (54%), myalgia (44%), and general musculoskeletal pain have been reported.

Other

Other side effects have included reports of jaw pain in 54% of patients on chronic infusions. Chills, fever, sepsis, and flu-like symptoms have been reported in 25% of patients. Ascites and pleural effusions have been reported. Adverse effects due to mechanical problems with the infusion pump have occurred. Tachyphylaxis, defined as an increased requirement for epoprostenol (the active ingredient contained in Flolan) over time (due to tolerance to the drug and not due to disease progression) has been reported. In general, doses of epoprostenol will need to be increased routinely.

Barst et al (1994) reported that 5 of 18 patients experienced 8 mechanical problems, including pump malfunction, and problems with syringe, tubing and catheter systems. When the epoprostenol was temporarily discontinued to remedy the problems, the patients experienced increased pulmonary hypertension symptoms, including syncope. One episode was fatal. Clotting occurred 9 times in 5 patients. One episode, resulting in sepsis, was fatal.

Jones and colleagues report the occurrence of sterile ascites in 3 patients during long-term epoprostenol treatment. Protein content and aspartate aminotransferases levels were elevated. In 2 patients the ascites was recurrent. Death occurred in one patient whose ascites was chylous (thick milky-white or pale yellow appearance).

Hematologic

Hematologic side effects have included reports of sepsis, usually due to infections from the indwelling catheter tip. Thrombocytopenia has been observed during uncontrolled clinical trials; however, it is not known if clinically significant bleeding occurred due to thrombocytopenia.

Barst and colleagues (1994) reported 7 episodes of nonfatal sepsis due to catheter tips in 3 of 18 patients receiving epoprostenol for primary pulmonary hypertension. One patient died due to sepsis after a thrombus was removed from the catheter. Jones and colleagues report that 3 of 10 patients acquired septicemia due to catheter tip infections. In each case, subjective wellbeing and exercise capacity decreased. Antibiotics were effective; however, in one patient a peripheral line had to be placed until the infection cleared.

Endocrine

Endocrine side effects have included rare reports of sweating during acute dosing.

Respiratory

Respiratory side effects have included rare report of dyspnea during acute dosing. Additional side effects have included hypoxia and pulmonary edema.

Local

Local side effects have included injection site pain (13%) and local infection (21%).

Peripheral venous local reactions (bright red veins, induration, tenderness) have been noted with epoprostenol infusion, but have resolved within 30 minutes after discontinuation of the infusion. The high pH of the buffer may have been responsible.

Psychiatric

Psychiatric side effects have included reports of depression.

Psychiatric side effects have included reports of depression in women receiving epoprostenol infusions for Raynaud's phenomenon or systemic sclerosis. Antidepressant therapy was successful in several cases.

Ocular

Ocular side effects have included reports of photosensitivity.

Dermatologic

Dermatologic side effects have included rash.

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