1 Dosing Considerations FLOLAN is not to be used for bolus administration. FLOLAN is only indicated for continuous intravenous infusion. FLOLAN, epoprostenol powder for injection Page 5 of 42 During acute dose-ranging, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output occurred rarely.
In such cases, dose reduction should be considered, but such an increase does not imply that chronic treatment is contraindicated. However, in the rare occurrence of pulmonary edema, chronic treatment is contraindicated. During chronic use, FLOLAN is delivered continuously on an ambulatory basis through a permanent indwelling central venous catheter.
Unless contraindicated, anticoagulant therapy should be administered to patients with idiopathic or heritable PAH receiving FLOLAN to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale.
In order to reduce the risk of infection, aseptic technique must be used in the reconstitution and administration of FLOLAN as well as in routine catheter care. Because FLOLAN is metabolized rapidly, even brief interruptions in the delivery of FLOLAN may result in symptoms associated with rebound PAH including dyspnea, dizziness, and asthenia.
The decision to initiate therapy with FLOLAN should be based upon the understanding that there is a high likelihood that intravenous therapy with FLOLAN will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a permanent intravenous catheter and infusion pump should be carefully considered.
FLOLAN can be used in acute vasoreactivity studies, to assess pulmonary vasodilator capacity. 2 Recommended Dose and Dosage Adjustment Initial Dosage Chronic infusion of FLOLAN should be initiated at 2 ng/kg/min and increased until dose-limiting pharmacological effects are elicited or until a tolerance limit to the drug is established and further increases in the infusion rate are not clinically warranted (see Dosage Adjustments below).
If dose- limiting pharmacologic effects occur, the infusion rate should be decreased to an appropriate chronic infusion rate whereby the pharmacologic effects of FLOLAN are tolerated. In clinical trials, the most common dose-limiting adverse events were nausea, vomiting, hypotension, sepsis, headache, abdominal pain, or respiratory disorder (most treatment limiting adverse events were not serious).
If the initial infusion rate of 2 ng/kg per minute is not tolerated, a lower dose which is tolerated by the patient should be identified. 2 ng/kg/min. 1 ng/kg/min on day 7 of treatment. 2 ng/kg/min. The mean incremental increase was 2 to 3 ng/kg/min every 3 weeks.
Dosage Adjustments Changes in the chronic infusion rate should be based on persistence, recurrence or worsening of the patient's symptoms of PAH and the occurrence of adverse events due to excessive doses of FLOLAN. In general, the need for increases in dose from the initial chronic dose should be expected over time.
Incremental increases in dose should be considered if symptoms of PAH persist or recur after improving. The infusion should be increased by 1 to 2 ng/kg/min increments at intervals sufficient to allow assessment of clinical response and tolerability; these intervals should be of at least 15 minutes.
Following establishment of a new chronic infusion rate, the patient should be observed, and standing and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated. During chronic infusion, the occurrence of dose-limiting pharmacologic events may necessitate a FLOLAN, epoprostenol powder for injection Page 6 of 42 decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment.
Dosage decreases should generally be made gradually in 2 ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve. Abrupt withdrawal of FLOLAN or sudden large reductions in infusion rates should be avoided.
g. ), infusion rates of FLOLAN should be adjusted only under the direction of a physician (see General). In patients receiving lung transplants, doses of FLOLAN were tapered after the initiation of cardiopulmonary bypass. 3 Reconstitution The diluent and reconstituted solution should be inspected visually for any particulate matter and/or abnormal physical appearance.
In the event of either being observed, the diluent or reconstituted solution should be discarded. FLOLAN IS ONLY STABLE WHEN RECONSTITUTED WITH pH 12 STERILE DILUENT for FLOLAN. FLOLAN MUST NOT BE RECONSTITUTED OR MIXED WITH ANY OTHER PARENTERAL MEDICATIONS OR SOLUTIONS PRIOR TO OR DURING ADMINISTRATION.
FLOLAN solution prepared with pH 12 STERILE DILUENT for FLOLAN must not be used with any preparation or administration material containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG). Physicians should ensure patients receive appropriate supplies if they self- administer FLOLAN, and patients should be directed to only use FLOLAN with the supplies provided.
A concentration for the solution of FLOLAN should be selected that is compatible with the infusion pump being used with respect to minimum and maximum flow rates, reservoir capacity, and the infusion pump criteria listed above. FLOLAN, when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump with a total reservoir volume of at least 100 mL.
FLOLAN should be prepared using 2 vials of pH 12 STERILE DILUENT for FLOLAN. Each vial is for single use only; discard any […]