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FLOLAN is a brand name for Epoprostenol, supplied as a powder for solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: FLOLAN (epoprostenol powder for injection) is indicated for the long-term intravenous treatment of idiopathic or heritable pulmonary arterial hypertension (PAH) or PAH associated with connective tissue diseases (CTD) in patients with WHO Functional Class III-IV symptoms who did not respond adequately to conventional…
Verbatim from this product's HC label. Tap a section to expand.
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).
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. During clinical trials, adverse events were classified as follows: (1) adverse events during dose escalation, (2) adverse events during chronic administration, and (3) adverse events associated with the drug delivery system.
Adverse Events During Dose Escalation In early clinical trials, FLOLAN was increased in 2 ng/kg/min increments until such time as the patients developed symptomatic intolerance. e. vasodilation. Table 7 lists the adverse events reported during dose escalation in decreasing order of frequency as well as the percent of cases where the event was dose limiting.
Age related differences (< 16 vs ≥16 years) in the incidence of adverse events are shown in Table 8. g. dizziness, syncope). Adverse events probably related to the underlying disease include dyspnea, fatigue, chest pain, edema, hypoxia, right ventricular failure and pallor.
Several adverse events, on the other hand, can clearly be attributed to FLOLAN. These include jaw pain, flushing, headache, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness. Adverse Events During Chronic Administration for Idiopathic or Heritable PAH In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 9 lists adverse events that occurred at a rate at least 10% different in the two groups in controlled trials for idiopathic or heritable PAH.
FLOLAN, epoprostenol powder for injection Page 16 of 42 Table 9 - Adverse Events Regardless of Attribution Occurring in Patients with Idiopathic or Heritable PAH During Chronic Administration in Controlled Trials with Greater than or Equal to 10 Percent Difference between FLOLAN and Conventional Therapy Alone Adverse Event FLOLAN (n=52) % of patients Conventional Therapya (n=54) % of patients Occurrence More Common with FLOLAN General Chills/Fever/Sepsis/Flu-like symptoms 25 11 Cardiovascular Tachycardia 35 24 Flushing 42 2 Gastrointestinal Diarrhea 37 6 Nausea/Vomiting 67 48 Musculoskeletal Jaw Pain 54 0 Myalgia 44 31 Non-specific musculoskeletal pain 35 15 Neurological Anxiety/nervousness/tremor 21 9 Dizziness 83 70 Headache 83 33 Hypesthesia, Hyperesthesia, Paresthesia 12 2 Occurrence More Common with Conventional Therapy Cardiovascular Heart Failure 31 52 Syncope 13 24 Shock 0 13 Respiratory Hypoxia 25 37 a Conventional therapy varied among patients and included some or all of the following: anticoagulants, supplemental oxygen, diuretics, oral vasodilators, and digoxin.
03/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES .............................................................................................
2 TABLE OF CONTENTS ............................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION .......................................................................
4 1 INDICATIONS ................................................................................................................ 1 Pediatrics .................................................................................................................
2 Geriatrics ................................................................................................................. 4 2 CONTRAINDICATIONS ..................................................................................................
4 4 DOSAGE AND ADMINISTRATION .................................................................................. 1 Dosing Considerations ............................................................................................. 2 Recommended Dose and Dosage Adjustment ........................................................
3 Reconstitution ......................................................................................................... 4 Administration .........................................................................................................
9 5 OVERDOSAGE............................................................................................................... 9 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................ 10 7 WARNINGS AND PRECAUTIONS .................................................................................
• FLOLAN is contraindicated in patients with known or suspected hypersensitivity to the drug or any of its excipients, to structurally-related compounds, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• The chronic use of FLOLAN in patients with congestive heart failure (CHF) due to severe left ventricular systolic dysfunction is contraindicated. A large study evaluating the effect of FLOLAN on survival in NYHA Class III and IV patients with CHF due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving FLOLAN plus conventional therapy than in those receiving conventional therapy alone.
• FLOLAN should not be used chronically in patients who develop pulmonary edema during dose initiation (see Pulmonary Edema).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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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 […]
g. pulmonary, gastrointestinal, epistaxis, intracranial, post-procedural, retroperitoneal) have been reported during uncontrolled clinical trials and post marketing clinical use in patients receiving FLOLAN. Table 10 lists those additional adverse events reported in patients with idiopathic or heritable PAH receiving FLOLAN plus conventional therapy versus conventional therapy alone during controlled clinical trials where the difference in incidence of the event between treatment groups was < 10%.
FLOLAN, epoprostenol powder for injection Page 17 of 42 Table 10 - Adverse Events Regardless of Attribution Occurring During Chronic Administration in Controlled Trials with Less than 10 Percent Difference between FLOLAN and Conventional Therapy Alone Adverse Event FLOLAN (n=52) % of patients Conventional Therapy (n=54) % of patients GENERAL Asthenia 87 81 CARDIOVASCULAR Angina Pectoris 19 20 Arrhythmia 27 20 Bradycardia 15 9 Supraventricular tachycardia 8 0 Pallor 21 30 Cyanosis 31 39 Palpitation 63 61 Cerebrovascular accident 4 0 Hypotension 27 31 Myocardial ischemia 2 6 GASTROINTESTINAL Abdominal pain 27 31 Anorexia 25 30 Ascites 12 17 Constipation 6 2 METABOLIC Edema 60 63 Hypokalemia 6 4 Weight reduction 27 24 Weight gain 6 4 MUSCULOSKELETAL Arthralgia 6 0 Bone pain 0 4 Chest pain 67 65 NEUROLOGICAL Confusion 6 11 Convulsion 4 0 Depression 37 44 Insomnia 4 4 RESPIRATORY Cough increase 38 46 Dyspnea 90 85 Epistaxis 4 2 FLOLAN, epoprostenol powder for injection Page 18 of 42 Adverse Event FLOLAN (n=52) % of patients Conventional Therapy (n=54) % of patients Pleural effusion 4 2 SKIN AND APPENDAGES Pruritus 4 0 Rash 10 13 Sweating 15 20 SPECIAL […]
1 Special Populations................................................................................................ 1 Pregnant Women ............................................................................................ 2 Breast-feeding .................................................................................................
3 Pediatrics ......................................................................................................... 4 Geriatrics .........................................................................................................
13 8 ADVERSE REACTIONS ................................................................................................. 2 Clinical Trial Adverse Reactions .............................................................................
5 Post-Market Adverse Reactions ............................................................................ 21 9 DRUG INTERACTIONS ................................................................................................. 2 Drug Interactions Overview ...................................................................................
4 Drug-Drug Interactions .......................................................................................... 5 Drug-Food Interactions.......................................................................................... 6 Drug-Herb Interactions ..........................................................................................
7 Drug-Laboratory Test Interactions......................................................................... 22 10 CLINICAL PHARMACOLOGY ........................................................................................ 1 Mechanism of Action .......................................................................................
2 Pharmacodynamics ......................................................................................... 3 Pharmacokinetics ............................................................................................ 24 11 STORAGE, STABILITY AND DISPOSAL ..........................................................................
25 12 SPECIAL HANDLING INSTRUCTIONS ............................................................................ 26 PART II: SCIENTIFIC INFORMATION ........................................................................................
26 13 PHARMACEUTICAL INFORMATION ............................................................................. 26 14 CLINICAL TRIALS .........................................................................................................
1 Clinical Trials by Indication .............................................................................. 27 15 MICROBIOLOGY .........................................................................................................
29 16 NON-CLINICAL TOXICOLOGY ...................................................................................... 29 PATIENT MEDICATION INFORMATION ...................................................................................
33 FLOLAN, epoprostenol powder for injection Page 4 of 42 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS FLOLAN (epoprostenol powder for injection) is indicated for the long-term intravenous treatment of idiopathic or heritable pulmonary arterial hypertension (PAH) or PAH associated with connective tissue diseases (CTD) in patients with WHO Functional Class III-IV symptoms who did not respond adequately to conventional therapy.
Prior to initiation of therapy, the potential benefit of FLOLAN should be weighed against the risks associated with use of the drug and the presence of an indwelling central venous catheter. FLOLAN should be used only by clinicians experienced in the diagnosis and treatment of PAH.
The diagnosis of idiopathic or heritable PAH or PAH/CTD should be carefully established by […]