FINTEPLA- fenfluramine solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

fenfluramine (UNII: 2DS058H2CF) (fenfluramine - UNII:2DS058H2CF)

Available from:

UCB, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older. 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)] 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) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. 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 dose (8.6 mg/kg/day) for adverse effects on embryofetal development in rats, maternal plasma exposures (AUC) of fenfluramine and norfenfluramine (the major metabolite) were approximately 2 and 5 times, respectively, those in humans at the maximum recommended human dose (MRHD) of 26 mg/day. Oral administration of fenfluramine (0, 4.3, 8.6, 13.0 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at all doses and increases in fetal malformations (external and skeletal) at the highest dose tested, which was associated with maternal toxicity. A no-adverse-effect dose for adverse effects on embryofetal development in rabbits was not identified. At the lowest dose tested in rabbits (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were lower than those in humans at the MRHD. Oral administration of fenfluramine (0, 4.3, 8,6, or 34.6 mg/kg/day) to female rats throughout gestation and lactation resulted in marked increases in stillborn pups and neonatal offspring deaths at the highest dose tested and delayed growth and reflex development during the pre- weaning period at all doses. Maternal body weight gain was decreased at all doses during pregnancy and at the two highest doses during lactation. A no-effect dose for adverse effects on pre- and postnatal development in rats was not determined. At the lowest dose tested in rats (4.3 mg/kg/day), maternal plasma exposures of fenfluramine and norfenfluramine were approximately 0.5 and 3 times, respectively, those in humans at the MRHD. Risk Summary There are no data on the presence of fenfluramine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for FINTEPLA and any potential adverse effects on the breastfed infant from FINTEPLA or from the underlying maternal condition. Infertility In animal studies, oral administration of fenfluramine resulted in adverse reproductive effects in males and females at clinically relevant doses in the presence of parental toxicity [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of FINTEPLA for the treatment of seizures associated with DS and LGS have been established in patients 2 years of age and older. Use of FINTEPLA for the treatment of seizures associated with DS in patients 2 years of age and older is supported by two randomized, double-blind, placebo-controlled trials in 202 patients 2 to 18 years of age. Use of FINTEPLA for the treatment of seizures associated with LGS is supported by a randomized, double-blind, placebo-controlled study in 263 patients aged 2 to 35 years, including 187 patients less than 18 years [see Boxed Warning, Warnings and Precautions (5), Adverse Reaction (6.1), and Clinical Studies (14)]. FINTEPLA can cause decreases in appetite and weight. The growth of pediatric patients treated with FINTEPLA should be carefully monitored. Safety and effectiveness in patients less than 2 years of age have not been established. Juvenile Animal Data Oral administration of fenfluramine (0, 3.0, 7,8, or 17.3 mg/kg/day) to young rats for 10 weeks starting on postnatal day 7 resulted in reduced body weight and neurobehavioral changes (decreased locomotor activity and learning and memory deficits) at all doses tested. Neurobehavioral effects persisted after dosing was discontinued. Bone size was decreased at the mid and high doses; brain size was decreased at the highest dose. Partial or complete recovery was seen for these endpoints. A no-effect dose for postnatal developmental toxicity was not identified. The lowest dose tested (3.0 mg/kg/day) was associated with plasma fenfluramine exposures (AUC) less than that in humans at the maximum recommended human dose (MRHD) of 26 mg/day and norfenfluramine (metabolite) exposures (AUC) approximately 2 times that in humans at the MRHD. Clinical studies of FINTEPLA for the treatment of DS or LGS did not include patients 65 years of age and over to determine whether they respond differently from 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. In patients with estimated glomerular filtration rate (eGFR) 15 to 29 mL/min/1.73m2 , do not exceed the maximum daily dosage of FINTEPLA of 20 mg. In patients with eGFR 15 to 29 ml/min/1.73m2 and concomitant stiripentol use, do not exceed the maximum daily dosage of FINTEPLA of 17 mg [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. FINTEPLA has not been studied in patients with eGFR < 15 mL/min/1.73m2 . Combined molar exposures of fenfluramine and norfenfluramine were increased in subjects with various degrees of hepatic impairment (Child-Pugh Class A, B, and C), necessitating a dosage adjustment in these patients [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)] . Be sure that you read, understand, and follow these instructions before you start using FINTEPLA oral solution and each time you get a refill. There may be new information. This Instructions for Use contains information on how to take FINTEPLA. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. What is included with FINTEPLA? The following items are included to prepare and give an oral dose of FINTEPLA: - 1 bottle of FINTEPLA oral solution (2.2 mg/mL) - 2 reusable oral syringes 1 Bottle of FINTEPLA Oral Solution (2.2 mg/mL)    2 Oral Syringes Call the pharmacist at 1-844-288-5007 if you did not receive the items listed above, or if you need help using them. Important information about FINTEPLA - FINTEPLA is an oral medicine (taken by mouth) and is given 2 times each day . Follow your healthcare provider's instructions for taking or giving doses of FINTEPLA. - If you have questions about how to prepare or give FINTEPLA, contact your healthcare provider or call your pharmacist. - Always use the oral syringes provided with FINTEPLA to make sure the right dose is given. If you need a new syringe contact your pharmacist. Do not use a household teaspoon or tablespoon. Oral syringes provided with FINTEPLA by the pharmacy. With FINTEPLA you will receive 2 reusable oral syringes. Call the pharmacist at 1-844-288-5007 if you have any questions about the syringes provided with FINTEPLA. - The bottle of FINTEPLA oral solution, and - A clean, dry reusable oral syringe that was provided with FINTEPLA. - Do not use the medicine if the "Throw Away" (Discard) date has passed. - If the date is near, contact your pharmacy or healthcare provider to get a refill or new prescription. - If the date has passed, dispose of any unused FINTEPLA. - Set the cap aside (do not throw away). - If the bottle does not have an adapter, contact the pharmacist. - Always leave the adapter in place in the bottle of medicine. - Use the other oral syringe provided, or - Contact the pharmacist to get a new one. - If you draw out too much medicine: Leave the oral syringe in the adapter. Push the plunger slowly back into the syringe until you reach the prescribed dose. - Leave the oral syringe in the adapter. - Push the plunger slowly back into the syringe until you reach the prescribed dose. - If you see air bubbles in the medicine: Leave the oral syringe in the adapter. Pull the plunger further down. Allow the bubbles to rise to the tip of the syringe. Push the plunger in all the way. Slowly pull the plunger out to the prescribed dose. Note: Very small bubbles in the liquid are normal. - Leave the oral syringe in the adapter. - Pull the plunger further down. - Allow the bubbles to rise to the tip of the syringe. - Push the plunger in all the way. - Slowly pull the plunger out to the prescribed dose. Note: Very small bubbles in the liquid are normal. - Put the syringe back into adapter. - See steps 9 to 11 to adjust the dose, as needed. - Do not squirt or forcefully push the medicine into the back of the throat. This may cause choking. - Always leave the adapter in place in the bottle - The cap will fit over it. - Rinse the oral syringe with clean tap water and allow it to air dry after each use. - Make sure you rinse the inside of the syringe and the plunger. - Pull clean tap water into the syringe with the plunger and push it out several times to clean the syringe. - Remove the plunger from the barrel of the oral syringe - Rinse both parts under tap water - Make sure the syringe and plunger are completely dry before the next use. - The syringe is also safe to clean in the dishwasher. How should I store FINTEPLA? - Store FINTEPLA at room temperature between 68°F to 77°F (20°C to 25°C). - Do not refrigerate or freeze. - Keep the cap tightly closed and the bottle upright. - Store the FINTEPLA bottle and syringe together in a clean area. - Throw away (discard) any unused FINTEPLA 3 months after first opening the bottle or if the Discard After date on the package or bottle has passed. Whichever one comes first. - Keep FINTEPLA and all medicines out of the reach of children. Manufactured for: UCB, Inc., Smyrna, GA 30080 FINTEPLA® is a registered trademark of the UCB Group of Companies. ©2023. All rights reserved. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 9/2023

Product summary:

FINTEPLA oral solution is a clear, colorless, cherry flavored liquid containing 2.2 mg/mL fenfluramine and is supplied in a white plastic bottle with a child resistant closure as follows: Before dispensing, the pharmacist will insert a press-in bottle adapter into the dispensing bottle. The pharmacy will provide 3 mL or 6 mL calibrated oral dosing syringes. Store FINTEPLA at room temperature between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not refrigerate or freeze. Store the bottle and syringe together. Discard any unused portion 3 months after first opening the bottle or the "Discard After" date on the bottle, whichever is sooner.

Authorization status:

New Drug Application

Patient Information leaflet

UCB, Inc.
----------
MEDICATION GUIDE
FINTEPLA® (FIN-TEP-LA)
(FENFLURAMINE)
ORAL SOLUTION
This Medication Guide has been approved by the
U.S. Food and Drug Administration.
Revised: 9/2023
Read this Medication Guide before you start taking FINTEPLA 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 the most important information I should know about FINTEPLA?
FINTEPLA can cause serious side effects, including:
1.
Problems with the valves in the heart (valvular heart disease) and
high blood pressure in the
arteries of the lungs (pulmonary arterial hypertension) have been
associated with fenfluramine, the
active ingredient in FINTEPLA. Your healthcare provider will do a test
called an echocardiogram
to check your heart and for high blood pressure in the arteries of the
lungs before you start taking
FINTEPLA, again every 6 months during treatment, and one time 3 to 6
months after you take your
last dose of FINTEPLA.
Call your healthcare provider right away if you develop any of these
signs and symptoms of heart
or lung problems during treatment with FINTEPLA:
•
shortness of breath
•
tiredness or weakness, especially with
increased activity
•
lightheadedness or fainting
•
swollen ankles or feet
•
chest pain
•
sensations of a rapid, fluttering heartbeat
(palpitations)
•
irregular pulse
•
bluish color to your lips and skin
(cyanosis)
Because of the risk of heart valve problems (valvular heart disease)
and high blood pressure in
arteries of lungs (pulmonary arterial hypertension) FINTEPLA is only
available through a restricted
program called the FINTEPLA Risk Evaluation and Mitigation Strategy
(REMS) Program. Before
you or your child receives FINTEPLA, your healthcare provider or
pharmacist will make sure you
understand how to take FINTEPLA safely. If you have any questions
about FINTEPLA, ask your
healthcare provider, visit www.FinteplaREMS.com, or call
1-877-964-3

Summary of Product characteristics

FINTEPLA- FENFLURAMINE SOLUTION
UCB, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
FINTEPLA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR FINTEPLA.
FINTEPLA (FENFLURAMINE) ORAL SOLUTION
INITIAL U.S. APPROVAL: 1973
WARNING: VALVULAR HEART DISEASE AND PULMONARY ARTERIAL HYPERTENSION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
THERE IS AN ASSOCIATION BETWEEN SEROTONERGIC DRUGS WITH 5-HT2B
RECEPTOR AGONIST
ACTIVITY, INCLUDING FENFLURAMINE (THE ACTIVE INGREDIENT IN FINTEPLA),
AND 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)
RECENT MAJOR CHANGES
Dosage and Administration (2.5)
1/2023
INDICATIONS AND USAGE
FINTEPLA is indicated for the treatment of seizures associated with
Dravet syndrome and Lennox-Gastaut
syndrome in patients 2 years of age and older. (1)
DOSAGE AND ADMINISTRATION
FINTEPLA is to be administered orally and may be taken with or without
food. (2.2)
Dravet Syndrome
The initial starting and maintenance dosage is 0.1 mg/kg twice daily,
which can be increased weekly
based on efficacy and tolerability. (2.2)
The maximum daily maintenance dosage of FINTEPLA is 0.35 mg/kg twice
daily (maximum daily
dosage of 26 mg). (2.2)
Lennox-Gastaut Syndrome
The initial starting dosage is 0.1 mg/kg twice daily, which should be
increased weekly based on
tolerability. (2.2)
The recommended maintenance dosage of FINTEPLA is 0.35 mg/kg twice
daily (maximum daily
dosage of 26 mg). (2.2)
Dravet Syndrome and Lennox-Gastaut Syndrome
Dose adjustment is required in patients taking concomitant stiripentol
plus clobazam: the maximum
daily maintenance dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum
daily dosage of 17 mg).
(2.2, 2.3, 2.4, 7.1)
Dosage adjustment is recommended in patients:
Taking strong CYP1A2 or CY