EPIDIOLEX- cannabidiol solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CANNABIDIOL (UNII: 19GBJ60SN5) (CANNABIDIOL - UNII:19GBJ60SN5)

Available from:

Jazz Pharmaceuticals, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

EPIDIOLEX is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients 1 year of age and older. EPIDIOLEX is contraindicated in patients with a history of hypersensitivity to cannabidiol or any of the ingredients in the product [see Description (11) and Warnings and Precautions (5.4)].   Pregnancy Surveillance Program and Pregnancy Exposure Registry There are two programs, an EPIDIOLEX pregnancy surveillance program and an antiepileptic drug (AED) pregnancy exposure registry, that monitor pregnancy outcomes.  Encourage women who are taking EPIDIOLEX during pregnancy to enroll in both, by calling the toll free numbers or visiting the websites below: Risk Summary There are no adequate data on the developmental risks associated with the use of EPIDIOLEX in pregnant women.  Administration of cannabidiol to pregnant animals produced evidence of developmental toxicity (increased embryofetal mortality in rats and decreased fetal body weights in rabbits; decreased growth, delayed sexual maturation, long-term neurobehavioral changes, and adverse effects on the reproductive system in rat offspring) at maternal plasma exposures similar to (rabbit) or greater than (rat) that in humans at therapeutic doses (see Animal Data).   In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. The background risks of major birth defects and miscarriage for the indicated populations are unknown. Data Animal Data Oral administration of cannabidiol (0, 75, 150, or 250 mg/kg/day) to pregnant rats throughout the period of organogenesis resulted in embryofetal mortality at the highest dose tested.  There were no other drug-related maternal or developmental effects.  The highest no-effect dose for embryofetal toxicity in rats was associated with maternal plasma cannabidiol exposures (AUC) approximately 16 and 9 times that in humans at the recommended human doses (RHD) of 20 and 25 mg/kg/day, respectively. Oral administration of cannabidiol (0, 50, 80, or 125 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in decreased fetal body weights and increased fetal structural variations at the highest dose tested, which was also associated with maternal toxicity.  Maternal plasma cannabidiol exposures at the no-effect level for embryofetal developmental toxicity in rabbits were less than that in humans at the RHDs. When cannabidiol (75, 150, or 250 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, decreased growth, delayed sexual maturation, neurobehavioral changes (decreased activity), and adverse effects on male reproductive organ development (small testes in adult offspring) and fertility were observed in the offspring at the mid and high dose.  These effects occurred in the absence of maternal toxicity.  The no-effect dose for pre- and post-natal developmental toxicity in rats was associated with maternal plasma cannabidiol exposures approximately 9 and 5 times that in humans at the RHDs of 20 and 25 mg/kg/day, respectively. Risk Summary There are no data on the presence of cannabidiol 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 EPIDIOLEX and any potential adverse effects on the breastfed infant from EPIDIOLEX or from the underlying maternal condition. Safety and effectiveness of EPIDIOLEX for the treatment of seizures associated with LGS, DS, or TSC have been established in patients 1 year of age and older.  The use of EPIDIOLEX in these indications is supported by adequate and well-controlled studies in patients 2 years of age and older with LGS and DS and in patients 1 year of age and older with TSC [see Clinical Studies (14.1, 14.2, 14.3)]. Safety and effectiveness of EPIDIOLEX in pediatric patients below 1 year of age have not been established. Juvenile Animal Data Administration of cannabidiol (subcutaneous doses of 0 or 15 mg/kg on Postnatal Days (PNDs) 4-6 followed by oral administration of 0, 100, 150, or 250 mg/kg on PNDs 7-77) to juvenile rats for 10 weeks resulted in increased body weight, delayed male sexual maturation, neurobehavioral effects (decreased locomotor activity and auditory startle habituation), increased bone mineral density, and liver hepatocyte vacuolation.  A no-effect dose was not established.  The lowest dose causing developmental toxicity in juvenile rats (15 sc/100 po mg/kg) was associated with cannabidiol exposures (AUC) approximately 15 and 8 times that in humans at the RHDs of 20 and 25 mg/kg/day, respectively. Clinical trials of EPIDIOLEX in the treatment of LGS, DS, and TSC did not include a sufficient number of patients aged above 55 years to determine whether or not 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 [see Dosage and Administration (2.6), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)] . Because of an increase in exposure to EPIDIOLEX, dosage adjustments are necessary in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.6), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)] .  EPIDIOLEX does not require dosage adjustments in patients with mild hepatic impairment. EPIDIOLEX is not a controlled substance. Animal abuse-related studies show that cannabidiol does not produce cannabinoid-like behavioral responses, including generalization to delta-9-tetrahydrocannabinol (THC) in a drug discrimination study. Cannabidiol also does not produce animal self-administration, suggesting it does not produce rewarding effects.  In a human abuse potential study, acute administration of cannabidiol to non-dependent adult recreational drug users at therapeutic and supratherapeutic doses of 750, 1500, and 4500 mg in the fasted state (equivalent respectively to 10, 20, and 60 mg/kg in a 75 kg adult) produced responses on positive subjective measures such as Drug Liking and Take Drug Again that were within the acceptable placebo range.  In contrast, 10 and 30 mg of dronabinol (synthetic THC) and 2 mg alprazolam produced large increases on positive subjective measures compared to placebo that were statistically significantly greater than those produced by cannabidiol.  In other Phase 1 clinical studies conducted with cannabidiol, there were no reports of abuse-related adverse events. In a human physical dependence study, administration of cannabidiol 1500 mg/day (750 mg twice daily) to adults for 28 days did not produce signs or symptoms of withdrawal over a 6-week assessment period  beginning three days after drug discontinuation.  This suggests that cannabidiol likely does not produce physical dependence. INSTRUCTIONS FOR USE EPIDIOLEX® (EH-peh-DYE-oh-lex) (cannabidiol) oral solution 100 mg/mL Be sure that you read, understand and follow these instructions carefully to ensure proper dosing of the oral solution. Important: Each package contains: Child-resistant cap 2 Bottle adapters 1 bottle of EPIDIOLEX oral solution (100 mg/mL) 2  reusable 1 mL oral syringes and 2 reusable 5 mL oral syringes: If your dose of EPIDIOLEX is 1 mL or less , use the 1 mL syringes to take your medicine. For each syringe size:                            Note: If you lose or damage an oral syringe, or cannot read the markings, use the spare syringe. Prepare The Bottle- to use EPIDIOLEX for the first time              Note: Do not remove the bottle adapter from the bottle after it is inserted. Prepare The Dose Your healthcare provider will tell you how much EPIDIOLEX to take or give.               Dose                                                                     How to measure                1 mL or less                                                           Use the 1 mL oral syringe 1 time                More than 1 mL and less than 5 mL                        Use the 5 mL oral syringe 1 time                More than 5 mL                                                     Use the 5 mL oral syringe more than 1 time              Line up the end of the plunger with the marking for your dose of EPIDIOLEX.                If there are air bubbles in the oral syringe, keep the bottle upside down and push the plunger so that all of the                liquid flows back into the bottle. Repeat Step 5 until the air bubbles are gone. Give EPIDIOLEX              Do not forcefully push on the plunger.              Do not direct the medicine to the back of the mouth or throat. This may cause choking.              If the dose of EPIDIOLEX prescribed by the healthcare provider is more than 5 mL, repeat steps 4 through 8  to complete the dose.                 For example:                 If your dose of EPIDIOLEX is 8 mL, withdraw 5 mL of medicine into the syringe and give the medicine.                 Insert the tip of the oral syringe back into the bottle adapter and withdraw 3 mL of medicine. Give the                 medicine to receive a total dose of 8 mL. Clean Up                Do not remove the bottle adapter. The cap will fit over it.                Do not wash the oral syringe in the dishwasher.           Do not throw away the oral syringe. How should I store EPIDIOLEX? Helpline Details For additional assistance, call the toll-free helpline at 1-833-426-4243. Hours: Monday-Friday                                       08:00am – 08:00pm EST Frequently Asked Questions Q:  What if there are air bubbles in the oral syringe? A:   Push the liquid back into the bottle and repeat Step 5 until the air bubbles are gone. Q:  What should I do if the liquid in the bottle has turned cloudy? A:  The liquid in the bottle may turn cloudy if water gets in the bottle. This does not change the safety or how well the medicine works. Continue to use the cloudy liquid as prescribed by your healthcare provider. Always make sure the oral syringes are completely dry before each use. Q:  What should I do if the oral syringe is not completely dry before use? A:  If the oral syringe is not completely dry, use the spare syringe provided in the pack.  Distributed by: Jazz Pharmaceuticals, Inc. Palo Alto, CA 94304 EPIDIOLEX® is a registered trademark of Jazz Pharmaceuticals plc or its subsidiaries. © 2023 Jazz Pharmaceuticals, Inc. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 01/2023

Product summary:

EPIDIOLEX is a strawberry-flavored, clear, colorless to yellow solution supplied in an amber glass bottle with a child-resistant closure.  EPIDIOLEX is available in bottles containing 60 mL (NDC 70127-100-06) or 100 mL of oral solution (NDC 70127-100-01).  Each mL contains 100 mg of cannabidiol.  EPIDIOLEX is packaged in a carton with two 1 mL calibrated oral dosing syringes, two 5 mL calibrated oral dosing syringes, and bottle adapters (NDC 70127-100-60 or NDC 70127‑100‑10). Store EPIDIOLEX in an upright position at 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 freeze.  Keep the cap tightly closed.  Use within 12 weeks of first opening the bottle, then discard any remainder.

Authorization status:

New Drug Application

Patient Information leaflet

Jazz Pharmaceuticals, Inc.
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MEDICATION GUIDE
EPIDIOLEX® (EH-peh-DYE-oh-lex)
(cannabidiol)
oral solution
Read this Medication Guide before you start taking EPIDIOLEX 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 EPIDIOLEX?
EPIDIOLEX can cause serious side effects, including:
1.
EPIDIOLEX may cause liver problems. Your healthcare provider may order
blood tests to check
your liver before you start taking EPIDIOLEX and during treatment. In
some cases, EPIDIOLEX
treatment may need to be stopped. Call your healthcare provider right
away if you develop any of
these signs and symptoms of liver problems during treatment with
EPIDIOLEX:
• loss of appetite, nausea, vomiting
• fever, feeling unwell, unusual tiredness
• yellowing of the skin or the whites of the eyes (jaundice)
• itching
• unusual darkening of the urine
• right upper stomach area pain or discomfort
2.
EPIDIOLEX may cause you to feel sleepy, which may get better over
time. Using certain
medicines with EPIDIOLEX such as clobazam or alcohol may increase
sleepiness. Do not drive,
operate heavy machinery, or do other dangerous activities until you
know how EPIDIOLEX affects
you.
3.
Like other antiepileptic drugs, EPIDIOLEX may cause suicidal thoughts
or actions in a very small
number of people, about 1 in 500.
Call a healthcare provider right away if you have any of these
symptoms, especially if they are
new, worse, or worry you:
• thoughts about suicide or dying
• attempt to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood
How can I w

Summary of Product characteristics

EPIDIOLEX- CANNABIDIOL SOLUTION
JAZZ PHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EPIDIOLEX SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR EPIDIOLEX.
EPIDIOLEX (CANNABIDIOL) ORAL SOLUTION
INITIAL U.S. APPROVAL: 2018
RECENT MAJOR CHANGES
Warnings and Precautions (5.1) 3/2024
INDICATIONS AND USAGE
EPIDIOLEX is indicated for the treatment of seizures associated with
Lennox-Gastaut syndrome, Dravet
syndrome, or tuberous sclerosis complex in patients 1 year of age and
older (1)
DOSAGE AND ADMINISTRATION
•
•
Seizures Associated with Lennox-Gastaut Syndrome or Dravet Syndrome
•
•
Seizures Associated with Tuberous Sclerosis Complex
•
Patients with Impaired Hepatic Function
•
DOSAGE FORMS AND STRENGTHS
Oral solution: 100 mg/mL (3)
CONTRAINDICATIONS
Hypersensitivity to cannabidiol or any of the ingredients in EPIDIOLEX
(4)
WARNINGS AND PRECAUTIONS
•
•
•
•
•
ADVERSE REACTIONS
The most common adverse reactions (10% or more for EPIDIOLEX and
greater than placebo) in patients
with Lennox-Gastaut syndrome or Dravet syndrome are: somnolence;
decreased appetite;
diarrhea; transaminase elevations; fatigue, malaise, and asthenia;
rash; insomnia, sleep disorder, and
poor quality sleep; and infections. (6.1)
®
®
Obtain serum transaminases (ALT and AST) and total bilirubin levels in
all patients prior to starting
treatment. (2.1, 5.1)
See Full Prescribing Information for titration. (2.2, 2.3)
The recommended starting dosage is 2.5 mg/kg by mouth twice daily (5
mg/kg/day). After one week,
the dosage can be increased to a maintenance dosage of 5 mg/kg twice
daily (10 mg/kg/day). (2.2)
Based on individual clinical response and tolerability, EPIDIOLEX can
be increased up to a maximum
recommended maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day).
The recommended starting dosage is 2.5 mg/kg by mouth twice daily (5
mg/kg/day). Increase the
dose weekly by 2.5 mg/kg twice daily (5 mg/kg/day), as tolerated,