The following Structured Product Label (SPL) was submitted to the FDA by Glaxosmithkline Llc for the product Flolan (NDC 0173-0519). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2.1 reconstitution, 2.2 dosage, 2.3 administration, 3 dosage forms and strengths, 4 contraindications, 5.1 pulmonary edema, 5.2 rebound pulmonary hypertension following abrupt withdrawal, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
FLOLAN® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise capacity. Trials establishing effectiveness included predominantly (97%) patients with New York Heart Association (NYHA) Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (49%) or PAH associated with connective tissue diseases (51%).
Each vial is for single use only; discard any unused diluent or unused reconstituted solution.
Select a concentration for the solution of FLOLAN 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 below [see Dosage and Administration (2.4)].
Using aseptic technique, reconstitute FLOLAN only with STERILE DILUENT for FLOLAN or pH 12 STERILE DILUENT for FLOLAN. Table 1 gives directions for preparing several different concentrations of FLOLAN. See Table 2 for storage and administration time limits for the reconstituted FLOLAN.
To make 100 mL of solution with final concentration of: | Directions: |
3,000 ng/mL | Dissolve contents of one 0.5‑mg vial with 5 mL of sterile diluent. Withdraw 3 mL and add to sufficient sterile diluent to make a total of 100 mL. |
5,000 ng/mL | Dissolve contents of one 0.5‑mg vial with 5 mL of sterile diluent. Withdraw entire vial contents and add sufficient sterile diluent to make a total of 100 mL. |
10,000 ng/mL | Dissolve contents of two 0.5‑mg vials each with 5 mL of sterile diluent. Withdraw entire vial contents and add sufficient sterile diluent to make a total of 100 mL. |
15,000 ng/mLa | Dissolve contents of one 1.5‑mg vial with 5 mL of sterile diluent. Withdraw entire vial contents and add sufficient sterile diluent to make a total of 100 mL. |
When Using STERILE DILUENT for FLOLAN | When Using pH 12 STERILE DILUENT for FLOLAN | |
Stability | When used at room temperature, (15°C to 25°C; 59°F to 77°F) reconstituted solutions:
When used with a cold pack, reconstituted solutions: | Freshly prepared reconstituted solutions or reconstituted solutions that have been stored at 2°C to 8°C (36°F to 46°F) for no longer than 8 days can be administered up to:
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Initiate intravenous infusions of FLOLAN at 2 ng/kg/min. Alter the infusion by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response. These intervals should be at least 15 minutes.
During dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output may occur. In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated.
Base changes in the chronic infusion rate on persistence, recurrence, or worsening of the patient's symptoms of pulmonary hypertension and the occurrence of adverse vasodilatory reactions. In general, expect progressive increases in dose.
If dose-related adverse reactions occur, make dose decreases gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve [see Adverse Reactions (6.1)]. Avoid abrupt withdrawal of FLOLAN or sudden large reductions in infusion rates [see Warnings and Precautions (5.2)].
Following establishment of a new chronic infusion rate, measure standing and supine blood pressure for several hours.
Taper doses of FLOLAN after initiation of cardiopulmonary bypass in patients receiving lung transplants.
Initiate FLOLAN in a setting with adequate personnel and equipment for physiologic monitoring and emergency care.
Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. If either particulate matter or discoloration is noted, do not use.
Administer continuous chronic infusion of FLOLAN through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Do not administer bolus injections of FLOLAN.
The ambulatory infusion pump used to administer FLOLAN should: (1) be small and lightweight, (2) be able to adjust infusion rates in 2‑ng/kg/min increments, (3) have occlusion, end-of-infusion, and low-battery alarms, (4) be accurate to ±6% of the programmed rate, and (5) be positive-pressure‑driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at infusion rates used to deliver FLOLAN. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. Use a 60-inch microbore non-di-(2-ethylhexyl)phthalate (DEHP) extension set with proximal antisyphon valve, low priming volume (0.9 mL), and in-line 0.22-micron filter.
To avoid interruptions in drug delivery, the patient should have access to a backup infusion pump and intravenous infusion sets.
Do not administer or dilute reconstituted solutions of FLOLAN with other parenteral solutions or medications. Consider a multi‑lumen catheter if other intravenous therapies are routinely administered.
Select a concentration for the solution of FLOLAN 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. When administered chronically, prepare FLOLAN in a drug delivery reservoir appropriate for the infusion pump with a total reservoir volume of at least 100 mL, using 2 vials of Sterile Diluent for flolan or 2 vials of pH 12 STERILE DILUENT for FLOLAN.
Generally, 3,000 ng/mL and 10,000 ng/mL are satisfactory concentrations to deliver between 2 to 16 ng/kg/min in adults. Higher infusion rates, and therefore, more concentrated solutions may be necessary with long‑term administration of FLOLAN.
Infusion rates may be calculated using the following formula:
Flolan Infusion Rate Formula (Flolan Spl Graphic 01)
For injection: 0.5 mg or 1.5 mg of epoprostenol, freeze-dried powder in a single-dose vial for reconstitution with the supplied diluent.
FLOLAN is contraindicated in patients with heart failure caused by reduced left ventricular ejection fraction [see Clinical Studies (14.3)].
FLOLAN is contraindicated in patients with a hypersensitivity to the drug or any of its ingredients.
If the patient develops pulmonary edema during initiation with FLOLAN, discontinue therapy and do not readminister. Consider the possibility of associated pulmonary veno-occlusive disease in such patients.
Avoid abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of FLOLAN because symptoms associated with rebound pulmonary hypertension (e.g., dyspnea, dizziness, and asthenia) may occur. In clinical trials, one Class III patient's death was judged attributable to the interruption of FLOLAN.
FLOLAN is a potent pulmonary and systemic vasodilator and can cause hypotension and other reactions such as flushing, nausea, vomiting, dizziness, and headache. Monitor blood pressure and symptoms regularly during initiation and after dose change [see Dosage and Administration (2.2)].
FLOLAN is a potent inhibitor of platelet aggregation. Therefore, expect an increased risk for hemorrhagic complications, particularly for patients with other risk factors for bleeding [see Clinical Pharmacology (12.3)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse reactions are shown in Table 3 and are generally related to vasodilatory effects.
Adverse Reaction | Idiopathic or Heritable PAH | PAH/SSD | ||
FLOLAN | Conventional Therapy | FLOLAN | Conventional Therapy | |
(n = 52) | (n = 54) | (n = 56) | (n = 55) | |
Body as a whole | ||||
Jaw pain | 54% | 0% | 75% | 0% |
Nonspecific musculoskeletal pain | 35% | 15% | 84% | 65% |
Headache | 83% | 33% | 46% | 5% |
Chills/fever/sepsis/flu-like symptoms | 25% | 11% | 13% | 11% |
Cardiovascular system | ||||
Flushing | 42% | 2% | 23% | 0% |
Hypotension | 27% | 31% | 13% | 0% |
Tachycardia | 35% | 24% | 43% | 42% |
Digestive system | ||||
Anorexia | 25% | 30% | 66% | 47% |
Nausea/Vomiting | 67% | 48% | 41% | 16% |
Diarrhea | 37% | 6% | 50% | 5% |
Skin and Appendages | ||||
Skin ulcer | - | - | 39% | 24% |
Eczema/rash/urticaria | 10% | 13% | 25% | 4% |
Musculoskeletal System | ||||
Myalgia | 44% | 31% | - | - |
Nervous system | ||||
Anxiety/hyperkinesias/nervousness/tremor | 21% | 9% | 7% | 5% |
Hyperesthesia/hypesthesia/paresthesia | 12% | 2% | 5% | 0% |
Dizziness | 83% | 70% | 59% | 76% |
Adverse Events Attributable to the Drug Delivery System
Chronic infusions of FLOLAN are delivered using a small, portable infusion pump through an indwelling central venous catheter. During controlled PAH trials of up to 12 weeks’ duration, the local infection rate was about 18%, and the rate for pain was about 11%. During long‑term follow‑up, sepsis was reported at a rate of 0.3 infections/patient per year in patients treated with FLOLAN.
The following events have been identified during postapproval use of FLOLAN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic
Anemia, hypersplenism, pancytopenia, splenomegaly, thrombocytopenia.
Endocrine and Metabolic
Hyperthyroidism.
Gastrointestinal
Hepatic failure.
Respiratory, Thoracic, and Mediastinal
Pulmonary embolism.
Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, FLOLAN should be used during pregnancy only if clearly needed.
Animal Data
Reproductive studies have been performed in pregnant rats and rabbits at doses up to 100 mcg/kg/day (600 mcg/m2/day in rats, 2.5 times the recommended human dose, and 1,180 mcg/m2/day in rabbits, 4.8 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to FLOLAN.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from FLOLAN, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
Clinical trials of FLOLAN in pulmonary hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Signs and Symptoms
Hypoxemia, hypotension, and respiratory arrest leading to death have been reported in clinical practice following overdosage of FLOLAN.
Excessive doses of FLOLAN were associated with flushing, headache, hypotension, tachycardia, nausea, vomiting, and diarrhea during clinical trials.
One patient with PAH/SSD accidentally received 50 mL of an unspecified concentration of FLOLAN. The patient vomited and became unconscious with an initially unrecordable blood pressure. FLOLAN was discontinued and the patient regained consciousness within seconds.
Single intravenous doses of FLOLAN at 10 and 50 mg/kg (2,703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
Treatment
Discontinue or reduce dose of FLOLAN.
FLOLAN (epoprostenol sodium) for injection is sterile sodium salt that is a white or off-white powder formulated for intravenous (IV) administration. Each vial of FLOLAN contains epoprostenol sodium equivalent to either 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol, 3.76 mg glycine, 50 mg mannitol, and 2.93 mg sodium chloride. Sodium hydroxide may have been added to adjust pH.
Epoprostenol (PGI2, PGX, prostacyclin), a metabolite of arachidonic acid, is a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. The chemical name of epoprostenol is (5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid. Epoprostenol sodium has a molecular weight of 374.45 and a molecular formula of C20H31NaO5. The structural formula is:
Epoprostenol Sodium Chemical Structure (Flolan Spl Graphic 02)
FLOLAN must be reconstituted with either STERILE DILUENT for FLOLAN or pH 12 STERILE DILUENT for FLOLAN.
STERILE DILUENT for FLOLAN is supplied in glass vials and pH 12 STERILE DILUENT for FLOLAN is supplied in plastic vials each containing 50 mL of 94 mg glycine, 73.3 mg sodium chloride, sodium hydroxide (added to adjust pH), and Water for Injection. The stability of reconstituted solutions of FLOLAN is pH-dependent, and is greater at higher pH.
Epoprostenol has 2 major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation.
Acute Hemodynamic Effects
Acute intravenous infusions of FLOLAN for up to 15 minutes in patients with idiopathic or heritable PAH or PAH/SSD produce dose‑related increases in cardiac index (CI) and stroke volume (SV) and dose‑related decreases in pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and mean systemic arterial pressure (SAPm). The effects of FLOLAN on mean pulmonary artery pressure (PAPm) were variable and minor.
In humans, hemodynamic changes due to epoprostenol (e.g., increased heart rate, facial flushing) returned to baseline within 10 minutes of termination of 60-minute infusions of 1 to 16 ng/kg/min. This pharmacodynamic behavior is consistent with a short in vivo half-life and rapid clearance in man, as suggested by the results of animal and in vitro studies.
In animals, the vasodilatory effects reduce right- and left-ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally-mediated bradycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying.
Drug Interactions
Additional reductions in blood pressure may occur when FLOLAN is administered with diuretics, antihypertensive agents, or other vasodilators.
When other antiplatelet agents or anticoagulants are used concomitantly, there is a potential for FLOLAN to increase the risk of bleeding. However, patients receiving infusions of FLOLAN in clinical trials were maintained on anticoagulants without evidence of increased bleeding.
Absorption/Distribution
Epoprostenol is rapidly hydrolyzed at neutral pH in blood and is also subject to enzymatic degradation. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol. Animal studies using tritium‑labeled epoprostenol have indicated a high clearance (93 mL/kg/min), small volume of distribution (357 mL/kg), and a short half‑life (2.7 minutes). During infusions in animals, steady‑state plasma concentrations of tritium‑labeled epoprostenol were reached within 15 minutes and were proportional to infusion rates.
Metabolism
Tritium‑labeled epoprostenol has been administered to humans in order to identify the metabolic products of epoprostenol. Epoprostenol is metabolized to 2 primary metabolites: 6‑keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. The recovery of radioactivity in urine and feces over a 1‑week period was 82% and 4% of the administered dose, respectively. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
Elimination
The in vitro half‑life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; therefore, the in vivo half‑life of epoprostenol in humans is expected to be no greater than 6 minutes.
Drug Interactions
In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide in whom therapy with FLOLAN was initiated, apparent oral clearance values for furosemide (n = 23) were decreased by 13% on the second day of therapy and returned to baseline values by Day 87. The change in furosemide clearance value is not likely to be clinically significant.
In a pharmacokinetic substudy in patients with congestive heart failure receiving digoxin in whom therapy with FLOLAN was initiated, apparent oral clearance values for digoxin (n = 30) were decreased by 15% on the second day of therapy and returned to baseline values by Day 87. Clinical significance of this interaction is not known.
Long‑term studies in animals have not been performed to evaluate carcinogenic potential. A micronucleus test in rats revealed no evidence of mutagenicity. The Ames test and DNA elution tests were also negative, although the instability of epoprostenol makes the significance of these tests uncertain. Fertility was not impaired in rats given FLOLAN by subcutaneous injection at doses up to 100 mcg/kg/day (600 mcg/m2/day, 2.5 times the recommended human dose [4.6 ng/kg/min or 245.1 mcg/m2/day, IV] based on body surface area).
Hemodynamic Effects
Chronic continuous infusions of FLOLAN in patients with idiopathic or heritable PAH were studied in 2 prospective, open, randomized trials of 8 and 12 weeks’ duration comparing FLOLAN plus conventional therapy with conventional therapy alone. Dosage of FLOLAN was determined as described in Dosage and Administration (2) and averaged 9.2 ng/kg/min at trials’ end. Conventional therapy varied among patients and included some or all of the following: anticoagulants in essentially all patients; oral vasodilators, diuretics, and digoxin in one-half to two-thirds of patients; and supplemental oxygen in about half the patients. Except for 2 NYHA Functional Class II patients, all patients were either functional Class III or Class IV. As results were similar in the 2 trials, the pooled results are described.
Chronic hemodynamic effects were generally similar to acute effects. Increases in CI, SV, and arterial oxygen saturation and decreases in PAPm, mean right atrial pressure (RAPm), TPR, and systemic vascular resistance (SVR) were observed in patients who received FLOLAN chronically compared with those who did not. Table 4 illustrates the treatment‑related hemodynamic changes in these patients after 8 or 12 weeks of treatment.
Baseline | Mean Change from Baseline at End of Treatment Perioda | |||
Hemodynamic Parameter | FLOLAN (n = 52) | Standard Therapy (n = 54) | FLOLAN (n = 48) | Standard Therapy (n = 41) |
CI (L/min/m2) | 2.0 | 2.0 | 0.3b | -0.1 |
PAPm (mm Hg) | 60 | 60 | -5b | 1 |
PVR (Wood U) | 16 | 17 | -4b | 1 |
SAPm (mm Hg) | 89 | 91 | -4 | -3 |
SV (mL/beat) | 44 | 43 | 6b | -1 |
TPR (Wood U) | 20 | 21 | -5b | 1 |
aAt 8 weeks: FLOLAN n = 10, conventional therapy n = 11 (n is the number of patients with hemodynamic data).
At 12 weeks: FLOLAN n = 38, conventional therapy n = 30 (n is the number of patients with hemodynamic data).
bDenotes statistically significant difference between group receiving FLOLAN and group receiving conventional therapy.
CI = Cardiac index, PAPm = Mean pulmonary arterial pressure, PVR = Pulmonary vascular resistance, SAPm = Mean systemic arterial pressure, SV = Stroke volume, TPR = Total pulmonary resistance.
These hemodynamic improvements appeared to persist when FLOLAN was administered for at least 36 months in an open, nonrandomized trial.
The acute hemodynamic response to FLOLAN did not correlate well with improvement in exercise tolerance or survival during chronic use of FLOLAN.
Clinical Effects
A statistically significant improvement was observed in exercise capacity, as measured by the 6‑minute walk test in patients receiving continuous intravenous FLOLAN plus conventional therapy (n = 52) for 8 or 12 weeks compared with those receiving conventional therapy alone (n = 54). Improvements were apparent as early as the first week of therapy. Increases in exercise capacity were accompanied by statistically significant improvement in dyspnea and fatigue, as measured by the Chronic Heart Failure Questionnaire and the Dyspnea Fatigue Index, respectively.
Survival was improved in NYHA Functional Class III and Class IV patients with idiopathic or heritable PAH treated with FLOLAN for 12 weeks in a multicenter, open, randomized, parallel trial. At the end of the treatment period, 8 of 40 (20%) patients receiving conventional therapy alone died, whereas none of the 41 patients receiving FLOLAN died (P = 0.003).
Hemodynamic Effects
Chronic continuous infusions of FLOLAN in patients with PAH/SSD were studied in a prospective, open, randomized trial of 12 weeks’ duration comparing FLOLAN plus conventional therapy (n = 56) with conventional therapy alone (n = 55). Except for 5 NYHA Functional Class II patients, all patients were either functional Class III or Class IV. In the controlled 12-week trial in PAH/SSD, for example, the dose increased from a mean starting dose of 2.2 ng/kg/min. During the first 7 days of treatment, the dose was increased daily to a mean dose of 4.1 ng/kg/min on Day 7 of treatment. At the end of Week 12, the mean dose was 11.2 ng/kg/min. The mean incremental increase was 2 to 3 ng/kg/min every 3 weeks.
Conventional therapy varied among patients and included some or all of the following: anticoagulants in essentially all patients, supplemental oxygen and diuretics in two-thirds of the patients, oral vasodilators in 40% of the patients, and digoxin in a third of the patients. A statistically significant increase in CI and statistically significant decreases in PAPm, RAPm, PVR, and SAPm after 12 weeks of treatment were observed in patients who received FLOLAN chronically compared with those who did not. Table 5 illustrates the treatment-related hemodynamic changes in these patients after 12 weeks of treatment.
Baseline | Mean Change from Baseline at 12 Weeks | |||
Hemodynamic Parameter | FLOLAN (n = 56) | Conventional Therapy (n = 55) | FLOLAN (n = 50) | Conventional Therapy (n = 48) |
CI (L/min/m2) | 1.9 | 2.2 | 0.5a | -0.1 |
PAPm (mm Hg) | 51 | 49 | -5a | 1 |
RAPm (mm Hg) | 13 | 11 | -1a | 1 |
PVR (Wood U) | 14 | 11 | -5a | 1 |
SAPm (mm Hg) | 93 | 89 | -8a | -1 |
aDenotes statistically significant difference between group receiving FLOLAN and group receiving conventional therapy (n is the number of patients with hemodynamic data).
CI = Cardiac index, PAPm = Mean pulmonary arterial pressure, RAPm = Mean right arterial pressure, PVR = Pulmonary vascular resistance, SAPm = Mean systemic arterial pressure.
Clinical Effects
Statistically significant improvement was observed in exercise capacity, as measured by the 6‑minute walk, in patients receiving continuous intravenous FLOLAN plus conventional therapy for 12 weeks compared with those receiving conventional therapy alone. Improvements were apparent in some patients at the end of the first week of therapy. Increases in exercise capacity were accompanied by statistically significant improvements in dyspnea and fatigue, as measured by the Borg Dyspnea Index and Dyspnea Fatigue Index. At Week 12, NYHA functional class improved in 21 of 51 (41%) patients treated with FLOLAN compared with none of the 48 patients treated with conventional therapy alone. However, more patients in both treatment groups (28/51 [55%] with FLOLAN and 35/48 [73%] with conventional therapy alone) showed no change in functional class, and 2/51 (4%) with FLOLAN and 13/48 (27%) with conventional therapy alone worsened.
No statistical difference in survival over 12 weeks was observed in patients with PAH/SSD treated with FLOLAN as compared with those receiving conventional therapy alone. At the end of the treatment period, 4 of 56 (7%) patients receiving FLOLAN died, whereas 5 of 55 (9%) patients receiving conventional therapy alone died.
A large trial evaluating the effect of FLOLAN on survival in NYHA Class III and IV patients with congestive heart failure 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. The chronic use of FLOLAN in patients with heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated.
FLOLAN for injection is supplied as a sterile freeze‑dried powder in 17‑mL flint glass vials with gray butyl rubber closures.
STERILE DILUENT for FLOLAN is supplied in flint glass vials containing 50‑mL diluent with fluororesin‑faced butyl rubber closures with aluminum overseal and yellow plastic flip-off cap.
pH 12 STERILE DILUENT for FLOLAN is supplied in plastic vials containing 50‑mL diluent with fluororesin‑faced butyl rubber closures with aluminum overseal and lavender plastic flip-off cap.
FLOLAN for injection | 0.5-mg (500,000 ng) per vial, carton of 1 | NDC 0173-0517-00 |
1.5-mg (1,500,000 ng) per vial, carton of 1 | NDC 0173-0519-00 | |
STERILE DILUENT for FLOLAN | 50 mL per vial, carton of 2 | NDC 0173-0518-01 |
pH 12 STERILE DILUENT for FLOLAN | 50 mL per vial, carton of 2 | NDC 0173-0857-02 |
Proper storage and handling are essential to maintain the potency of FLOLAN for injection.
Unopened vials of FLOLAN powder are stable until the date indicated on the package when stored at room temperature, 15°C to 25°C (59°F to 77°F) and protected from light in the carton.
Unopened vials of STERILE DILUENT for FLOLAN and pH 12 STERILE DILUENT for FLOLAN are stable until the date indicated on the package when stored at room temperature, 15°C to 25°C (59°F to 77°F). DO NOT FREEZE.
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients:
FLOLAN is a registered trademark of the GSK group of companies.
GlaxoSmithKline
Research Triangle Park, NC 27709
©2016 the GSK group of companies. All rights reserved.
FLL:5PI
PHARMACIST‑DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT
_ _ __ _ __ _ __ _ __ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _
FLOLAN® (flow-lan)
(epoprostenol sodium)
for injection
Read this Patient Information before you start taking FLOLAN and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.
What is FLOLAN?
FLOLAN is a prescription medicine used to treat people with certain types of pulmonary arterial hypertension (PAH), which is high blood pressure in the arteries of the lungs. FLOLAN can improve your ability to be physically active.
It is not known if FLOLAN is safe and effective in children.
Who should not use FLOLAN?
Do not use FLOLAN if you:
What should I tell my healthcare provider before using FLOLAN?
Before you use FLOLAN, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Especially tell your healthcare provider if you take:
Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.
Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine.
How should I use FLOLAN?
Using more than the prescribed dose of FLOLAN can lead to death. If you use more than the prescribed dose of FLOLAN, call your healthcare provider or go to the nearest emergency room right away.
What are the possible side effects of FLOLAN?
FLOLAN can cause serious side effects, including:
The most common side effects of FLOLAN include:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of FLOLAN. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store and use FLOLAN?
How to store mixed solutions of FLOLAN:
Keep FLOLAN and all medicines out of the reach of children.
General information about the safe and effective use of FLOLAN
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use FLOLAN for a condition for which it was not prescribed. Do not give FLOLAN to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about FLOLAN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about FLOLAN that is written for health professionals.
For more information, go to www.FLOLAN.com or call 1-888-825-5249.
What are the ingredients in FLOLAN?
Active ingredient: epoprostenol sodium.
Inactive ingredients: glycine, mannitol, sodium chloride. Sodium hydroxide may have been added.
The STERILE DILUENT for FLOLAN and the pH 12 STERILE DILUENT for FLOLAN contain: glycine, sodium chloride, sodium hydroxide, and Water for Injection.
This Patient Information has been approved by the U.S. Food and Drug Administration.
GlaxoSmithKline
Research Triangle Park, NC 27709
FLOLAN is a registered trademark of the GSK group of companies.
©2016 the GSK group of companies. All rights reserved.
Revised: June/2016
FLL:2PIL
PRINCIPAL DISPLAY PANEL
NDC 0173-0517-00
FLOLAN®
(epoprostenol sodium)
for Injection
0.5 mg/vial (500,000 ng/vial)
Must be reconstituted. For intravenous infusion after dilution.
Note: Use only STERILE DILUENT for FLOLAN or pH 12 STERILE DILUENT for FLOLAN for reconstitution and dilution.
Rx only
Single-Use Vial
Each vial contains epoprostenol sodium equivalent to 0.5 mg (500,000 ng) epoprostenol, 3.76 mg glycine, 2.93 mg sodium chloride, and 50 mg mannitol. Sodium hydroxide may have been added to adjust pH.
Usual Dose: See prescribing information.
Store at 15o and 25o C (59o to 77oF).
Do not accept if plastic overseal is missing or not securely fitted.
GlaxoSmithKline
RTP, NC 27709
Rev. 4/16
10000000140666
Flolan 0.5 mg Label (Flolan Spl Graphic 03)
PRINCIPAL DISPLAY PANEL
NDC 0173-0519-00
FLOLAN®
(epoprostenol sodium)
for Injection
1.5 mg/vial (1,500,000 ng/vial)
Must be reconstituted. For intravenous infusion after dilution.
Note: Use only STERILE DILUENT for FLOLAN or pH 12 STERILE DILUENT for FLOLAN for reconstitution and dilution.
Rx only
Single-Use Vial
Each vial contains epoprostenol sodium equivalent to 1.5 mg (1,500,000 ng) epoprostenol, 3.76 mg glycine, 2.93 mg sodium chloride, and 50 mg mannitol. Sodium hydroxide may have been added to adjust pH.
Usual Dose: See prescribing information.
Store at 15o and 25o C (59o to 77oF).
Do not accept if plastic overseal is missing or not securely fitted.
GlaxoSmithKline
RTP, NC 27709
Rev. 4/16
10000000140667
Flolan 1.5 mg Label (Flolan Spl Graphic 04)
PRINCIPAL DISPLAY PANEL
NDC 0173-0518-00
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