Fenfluramine
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Boxed warning
WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION FINTEPLA can cause valvular heart disease and pulmonary arterial hypertension [see Warnings and Precautions (5.1) ]. Echocardiogram assessments are required before, during, and after treatment with FINTEPLA. The benefits versus the risks of initiating or continuing FINTEPLA must be considered, based on echocardiogram findings [see Dosage and Administration (2.1 , 2.6 ) and Warnings and Precautions (5.1) ].
Because of the risks of valvular heart disease and pulmonary arterial hypertension, FINTEPLA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FINTEPLA REMS [see Warnings and Precautions (5.2) ]. WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION See full prescribing information for complete boxed warning. FINTEPLA can cause valvular heart disease and pulmonary arterial hypertension. ( 5.1 ) Echocardiogram assessments are required before, during, and after treatment with FINTEPLA. ( 2.1 , 2.6 , 5.1 ) FINTEPLA is available only through a restricted program called the FINTEPLA REMS. ( 5.2 )
Handling and access
REMS
RequiredStated in the label quoted on this page.
- Restricted distribution (ETASU)
- Prescriber certification or enrollment
- Pharmacy certification
- Patient enrollment
- Medication Guide
Dosing in kidney impairment
Dosage Modifications for Patients with Severe Renal Impairment (DS and LGS) For patients with severe renal impairment (estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m 2 ), a maximum total daily dosage of 20 mg without concomitant stiripentol and 17 mg with concomitant stiripentol plus clobazam is recommended [see Use in Specific Populations ] .
| Without concomitant stiripentol | With concomitant stiripentol plus clobazam | |||
|---|---|---|---|---|
| Weight-based Dosage To calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily | Maximum Total Daily Dosage For maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5. | Weight-based Dosage | Maximum Total Daily Dosage | |
| Initial Dosage For patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed. | 0.1 mg/kg twice daily | 26 mg | 0.1 mg/kg twice daily | 17 mg |
| Day 7 | 0.2 mg/kg twice daily | 26 mg | 0.15 mg/kg twice daily | 17 mg |
| Day 14 For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14). | 0.35 mg/kg twice daily | 26 mg | 0.2 mg/kg twice daily | 17 mg |
Dosing in liver impairment
Dosage Modifications for Patients with Mild, Moderate, and Severe Hepatic Impairment (DS and LGS) See Table 2 for dosage adjustments and recommendations for patients with hepatic impairment [see Use in Specific Populations ] . [See table below.] Severe (Child-Pugh C) 17 mg Use not recommended
| Without concomitant stiripentol | With concomitant stiripentol plus clobazam | |||
|---|---|---|---|---|
| Weight-based Dosage To calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily | Maximum Total Daily Dosage For maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5. | Weight-based Dosage | Maximum Total Daily Dosage | |
| Initial Dosage For patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed. | 0.1 mg/kg twice daily | 26 mg | 0.1 mg/kg twice daily | 17 mg |
| Day 7 | 0.2 mg/kg twice daily | 26 mg | 0.15 mg/kg twice daily | 17 mg |
| Day 14 For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14). | 0.35 mg/kg twice daily | 26 mg | 0.2 mg/kg twice daily | 17 mg |
| Hepatic Impairment Classification | Without concomitant stiripentol titrate as recommended [see Dosage and Administration (2.2)] | With concomitant stiripentol plus clobazam |
|---|---|---|
| Maximum total daily dosage | Maximum total daily dosage | |
| Mild (Child-Pugh A) | 20 mg | 13 mg |
| Moderate (Child-Pugh B) | 20 mg | Use not recommended |
| Severe (Child-Pugh C) | 17 mg | Use not recommended |
Preparation and administration
Assessments During and After Administration of FINTEPLA To evaluate for valvular heart disease and pulmonary arterial hypertension, obtain an echocardiogram assessment every 6 months during treatment with FINTEPLA, and 3 to 6 months after the final dose of FINTEPLA [see Warnings and Precautions ].
Administration Instructions A calibrated measuring device (either a 3 mL or 6 mL oral syringe) will be provided by the pharmacy and is recommended to measure and administer the prescribed dose accurately [see How Supplied/Storage and Handling ] . A household teaspoon or tablespoon is not an adequate measuring device and should not be used.
Discard any unused FINTEPLA oral solution remaining after 3 months of first opening the bottle or the "Discard After" date on the bottle, whichever is sooner. FINTEPLA is compatible with commercially available gastric and nasogastric feeding tubes.
| Without concomitant stiripentol | With concomitant stiripentol plus clobazam | |||
|---|---|---|---|---|
| Weight-based Dosage To calculate the dose volume: Weight (kg) × Weight-based dosage (mg/kg) ÷ 2.2 mg/mL = mL dose to be taken twice daily | Maximum Total Daily Dosage For maximum dosage with concomitant use of strong CYP1A2 or CYP2D6 inhibitors, in patients with severe renal impairment, or in patients with hepatic impairment see Dosage and Administration 2.3, 2.4, 2.5. | Weight-based Dosage | Maximum Total Daily Dosage | |
| Initial Dosage For patients with Dravet syndrome, dosage may be increased based on clinical response to the maximum recommended dosage, as needed. | 0.1 mg/kg twice daily | 26 mg | 0.1 mg/kg twice daily | 17 mg |
| Day 7 | 0.2 mg/kg twice daily | 26 mg | 0.15 mg/kg twice daily | 17 mg |
| Day 14 For patients with Lennox-Gastaut syndrome, dosage should be increased as tolerated to the recommended maintenance dosage (i.e., Day 14). | 0.35 mg/kg twice daily | 26 mg | 0.2 mg/kg twice daily | 17 mg |
Drug interactions
Check interactions
Add the patient's other drugs. Matches come from both FDA labels: by name, drug class, and enzyme or transporter pathway.
- Fenfluramine
Label text (7 paragraphs)
Dose adjustment is required for patients taking stiripentol plus clobazam. ( 2.2 , 2.3 , 7.1 ) Strong CYP1A2 or CYP2D6 inhibitors: a dose adjustment is recommended ( 2.3 , 7.1 ) Strong CYP1A2, CYP2B6, or CYP3A4 inducers: it is recommended to avoid coadministration with FINTEPLA. If coadministration is necessary, consider a FINTEPLA dosage increase. ( 7.1 )
7.1 Effect of Other Drugs on FINTEPLA Stiripentol Plus Clobazam Coadministration of FINTEPLA with stiripentol plus clobazam, with or without valproate, increases fenfluramine plasma concentrations [see Clinical Pharmacology (12.3) ]. If FINTEPLA is coadministered with stiripentol plus clobazam, the maximum daily dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg) [see Dosage and Administration (2.2) ] . Strong CYP1A2, CYP2B6, or CYP3A Inducers Coadministration of FINTEPLA with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of FINTEPLA [see Clinical Pharmacology (12.3) ] .
It is recommended to avoid coadministration of strong CYP1A2, CYP2B6 or CYP3A inducers. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed; however, do not exceed the maximum daily dosage of FINTEPLA [see Dosage and Administration (2.2) ]. If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer [see Warnings and Precautions (5.6) ].
Strong CYP1A2 or CYP2D6 Inhibitors Coadministration of FINTEPLA with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations [see Clinical Pharmacology (12.3) ] . If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg [see Dosage and Administration (2.3) ]. If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors; however, do not exceed the maximum daily dosage of FINTEPLA [see Dosage and Administration (2.2) ].
If FINTEPLA is coadministered with stiripentol and a strong CYP1A2 or CYP2D6 inhibitor, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.3) ].
7.2 Effects of Serotonin Receptor Antagonists Cyproheptadine and potent 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C serotonin receptor antagonists may decrease the efficacy of FINTEPLA. If cyproheptadine or potent 5--HT1A, 5--HT1D, 5-HT2A, or 5-HT2C serotonin receptor antagonists are coadministered with FINTEPLA, patients should be monitored appropriately.
7.3 Serotonergic Drugs Concomitant administration of FINTEPLA and drugs (e.g., SSRIs, SNRIs, TCAs, MAO inhibitors, trazodone, etc.), over-the-counter medications (e.g., dextromethorphan), or herbal supplements (e.g., St. John's Wort) that increase serotonin may increase the risk of serotonin syndrome [see Warnings and Precautions (5.7) ]. Concomitant use of FINTEPLA is contraindicated within 14 days of taking MAOIs. Use FINTEPLA with caution in patients taking other medications that increase serotonin.
Contraindications
4 CONTRAINDICATIONS FINTEPLA is contraindicated in patients with: Hypersensitivity to fenfluramine or any of the excipients in FINTEPLA [see Description (11) ] Concomitant use, or within 14 days of the administration, of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.7) ] Hypersensitivity to fenfluramine or any of the excipients in FINTEPLA ( 4 ) Within 14 days of the administration of monoamine oxidase inhibitors due to an increased risk of serotonin syndrome ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for fenfluramine. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as FINTEPLA, during pregnancy. Encourage women who are taking FINTEPLA during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary There are no data on FINTEPLA use in pregnant women.
Available data from epidemiologic studies with fenfluramine or dexfenfluramine are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. FINTEPLA can cause decreased appetite and decreased weight [see Warnings and Precautions (5.3) ]; monitor for adequate weight gain during pregnancy.
In animal studies, administration of fenfluramine throughout organogenesis (rat and rabbit) or throughout gestation and lactation (rat) resulted in adverse effects on development (fetal malformations, embryofetal and offspring mortality and growth impairment) in the presence of maternal toxicity at clinically relevant maternal plasma levels of fenfluramine and its major active metabolite (see Data ) . All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures.
Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including FINTEPLA, due to the risk of status epilepticus or severe seizures, which may be life-threatening [see Warnings and Precautions (5.6) ]. Data Animal Data Oral administration of fenfluramine (0, 4.5, 8.6, or 34.6 mg/kg/day) to pregnant rats during organogenesis resulted in decreased fetal body weights and marked increases in fetal malformations (external, visceral, and skeletal) at the highest dose tested, which was associated with maternal toxicity. At the no-effect…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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