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 inpatients 1 year of age and older (1)----------------------DOSAGE AND ADMINISTRATION----------------------•
Obtain serum transaminases (ALT and AST) and total bilirubin levels inall patients prior to starting treatment. (2.1, 5.1)•
See Full Prescribing Information for titration. (2.2, 2.3)
Seizures Associated with Lennox-Gastaut Syndrome or Dravet Syndrome•
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 canbe increased up to a maximum recommended maintenance dosage of
10 mg/kg twice daily (20 mg/kg/day).
Seizures Associated with Tuberous Sclerosis Complex•
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, to a recommended maintenance dosage of
12.5 mg/kg twice daily (25 mg/kg/day). (2.3)
Patients with Impaired Hepatic Function•
Dosage adjustment is recommended for patients with moderate or severe
hepatic impairment. (2.6, 8.6)•

the risk of transaminase elevations. See Full Prescribing Information forserum transaminase and bilirubin monitoring recommendations. (5.1)
Somnolence and Sedation: Monitor for somnolence and sedation andadvise patients not to drive or operate machinery until they have gained
sufficient experience on EPIDIOLEX. (5.2)
Suicidal Behavior and Ideation: Monitor patients for suicidal behavior
and thoughts. (5.3)
Hypersensitivity Reactions: Advise patients to seek immediate medicalcare. Discontinue and do not restart EPIDIOLEX if hypersensitivity
occurs. (5.4)
Withdrawal of Antiepileptic Drugs: EPIDIOLEX should be gradually
withdrawn to minimize the risk of increased seizure frequency and statusepilepticus. (5.5)------------------------------ADVERSE REACTIONS------------------------------The most common adverse reactions (10% or more for EPIDIOLEX andgreater 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, andpoor quality sleep; and infections. (6.1)
The most common adverse reactions (10% or more for EPIDIOLEX andgreater than placebo) in patients with tuberous sclerosis complex are:diarrhea; transaminase elevations; decreased appetite; somnolence; pyrexia;
and vomiting. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Jazz
Pharmaceuticals, Inc. at 1-800-520-5568 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.

---------------------DOSAGE FORMS AND STRENGTHS---------------------Oral solution: 100 mg/mL (3)-------------------------------DRUG INTERACTIONS-----------------------------•
Strong inducer of CYP3A4 or CYP2C19: Consider dose increase of
EPIDIOLEX. (7.1)•
Consider a dose reduction of substrates of UGT1A9, UGT2B7,
CYP1A2, CYP2C8, CYP2C9, CYP2C19 (e.g., clobazam), and orally
administered P-gp substrates. (7.2)•
A lower starting dose of orally administered everolimus isrecommended. (7.2)•
Substrates of CYP2B6 may also require dose adjustment. (7.2)-------------------------------CONTRAINDICATIONS-----------------------------Hypersensitivity to cannabidiol or any of the ingredients in EPIDIOLEX (4)-----------------------USE IN SPECIFIC POPULATIONS-----------------------Pregnancy: Based on animal data, may cause fetal harm. (8.1)-----------------------WARNINGS AND PRECAUTIONS-----------------------•
Hepatic Injury: EPIDIOLEX can cause transaminase elevations.
Concomitant use of valproate and higher doses of EPIDIOLEX increase

See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide
Revised: 3/2024

FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Assessments Prior to Initiating EPIDIOLEX
2.2 Dosing for Seizures Associated with Lennox-Gastaut Syndrome or
Dravet Syndrome
2.3 Dosing for Seizures Associated with Tuberous Sclerosis Complex
2.4 Administration Instructions
2.5 Discontinuation of EPIDIOLEX
2.6 Patients with Hepatic Impairment
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hepatic Injury
5.2 Somnolence and Sedation
5.3 Suicidal Behavior and Ideation
5.4 Hypersensitivity Reactions
5.5 Withdrawal of Antiepileptic Drugs (AEDs)
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on EPIDIOLEX
7.2 Effect of EPIDIOLEX on Other Drugs
7.3 Concomitant Use of EPIDIOLEX and Valproate
7.4 CNS Depressants and Alcohol
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy

8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Hepatic Impairment
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
9.2 Abuse
9.3 Dependence
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis and Mutagenesis
14 CLINICAL STUDIES
14.1 Lennox-Gastaut Syndrome
14.2 Dravet Syndrome
14.3 Tuberous Sclerosis Complex
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
17 PATIENT COUNSELING INFORMATION* Sections or subsections omitted from the full prescribing information are notlisted.

FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
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.
2 DOSAGE AND ADMINISTRATION
2.1 Assessments Prior to Initiating EPIDIOLEX
Because of the risk of hepatocellular injury, obtain serum transaminases (ALT and AST) and total bilirubinlevels in all patients prior to starting treatment with EPIDIOLEX [see Warnings and Precautions (5.1)].
2.2 Dosing for Seizures Associated with Lennox-Gastaut Syndrome or Dravet Syndrome• The 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).
• Patients who are tolerating EPIDIOLEX at 5 mg/kg twice daily and require further reduction of seizures
may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg
twice daily (20 mg/kg/day), in weekly increments of 2.5 mg/kg twice daily (5 mg/kg/day), as tolerated.
For patients in whom a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage
may be increased no more frequently than every other day. Administration of the 20 mg/kg/day dosage
resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10
mg/kg/day, but with an increase in adverse reactions.
2.3 Dosing for Seizures Associated with Tuberous Sclerosis Complex• The starting dosage is 2.5 mg/kg by mouth twice daily (5 mg/kg/day).
• Increase the dose in weekly increments of 2.5 mg/kg twice daily (5 mg/kg/day), as tolerated, to a
recommended maintenance dosage of 12.5 mg/kg twice daily (25 mg/kg/day). For patients in whom amore rapid titration to 25 mg/kg/day is warranted, the dosage may be increased no more frequently thanevery other day.
• The effectiveness of doses lower than 12.5 mg/kg twice daily has not been studied in patients with TSC.
2.4 Administration Instructions
Food may affect EPIDIOLEX levels [see Clinical Pharmacology (12.3)]. Consistent dosing of EPIDIOLEX
with respect to meals is recommended to reduce variability in cannabidiol plasma exposure.
Calibrated measuring devices (1 mL and 5 mL oral syringes) will be provided and are recommended to measureand deliver the prescribed dose accurately [see How Supplied/Storage and Handling (16.1)]. A household
teaspoon or tablespoon is not an adequate measuring device.
Oral administration is recommended. When necessary, EPIDIOLEX can be enterally administered via silicone
feeding tubes, such as nasogastric or gastrostomy tubes. The recommended volume for flushing (with room
temperature drinking water) after each dose is approximately 5 times the priming volume of the tube. The
flushing volume may need to be modified in patients with fluid restrictions. Do not use with tubes made ofpolyvinyl chloride (PVC) or polyurethane and avoid use of silicone nasogastric tubes with short lengths andnarrow diameters (e.g., less than 50 cm and less than 5 FR).
Discard any unused EPIDIOLEX remaining 12 weeks after first opening the bottle [see How Supplied/ Storageand Handling (16.2)].

2.5 Discontinuation of EPIDIOLEXWhen discontinuing EPIDIOLEX, the dose should be decreased gradually. As with most antiepileptic drugs,
abrupt discontinuation should be avoided when possible, to minimize the risk of increased seizure frequency
and status epilepticus [see Warnings and Precautions (5.5)].
2.6 Patients with Hepatic Impairment
Dose adjustment is recommended in patients with moderate (Child-Pugh B) hepatic impairment or severe(Child-Pugh C) hepatic impairment [see Warnings and Precautions (5.1), Use in Specific Populations (8.6), andClinical Pharmacology (12.3)]. It may be necessary to have slower dose titration in patients with moderate orsevere hepatic impairment than in patients without hepatic impairment (see Table 1).
EPIDIOLEX does not require dose adjustment in patients with mild (Child-Pugh A) hepatic impairment.
Table 1: Dose Adjustments in Patients with Hepatic Impairment
Hepatic
Starting Dosage
In Patients with LGS or DS
Impairment
Maintenance Dosage Range

In Patients with TSC
Maintenance Dosage

Mild

2.5 mg/kg twice daily(5 mg/kg/day)

5 to 10 mg/kg twice daily(10 to 20 mg/kg/day)

12.5 mg/kg twice daily(25 mg/kg/day)Moderate

1.25 mg/kg twice daily(2.5 mg/kg/day)

2.5 to 5 mg/kg twice daily(5 to 10 mg/kg/day)

6.25 mg/kg twice daily(12.5 mg/kg/day)Severe

0.5 mg/kg twice daily(1 mg/kg/day)

1 to 2 mg/kg twice daily(2 to 4 mg/kg/day)

2.5 mg/kg twice daily(5 mg/kg/day)

3 DOSAGE FORMS AND STRENGTHS
Cannabidiol oral solution: 100 mg/mL of a strawberry-flavored, clear, colorless to yellow solution.
4 CONTRAINDICATIONSEPIDIOLEX is contraindicated in patients with a history of hypersensitivity to cannabidiol or any of theingredients in the product [see Description (11) and Warnings and Precautions (5.4)].
5 WARNINGS AND PRECAUTIONS
5.1 Hepatic Injury
EPIDIOLEX can cause dose-related elevations of liver transaminases (alanine aminotransferase [ALT] and/or
aspartate aminotransferase [AST]). In controlled studies for LGS and DS (10 and 20 mg/kg/day dosages) andTSC (25 mg/kg/day), the incidence of ALT elevations above 3 times the upper limit of normal (ULN) was 13%(10 and 20 mg/kg/day dosages) and 12% (25 mg/kg/day dosage) in EPIDIOLEX-treated patients compared with
1% in patients on placebo. Less than 1% of EPIDIOLEX-treated patients had ALT or AST levels greater than
20 times the ULN. There were cases of transaminase elevations associated with hospitalization in patientstaking EPIDIOLEX. In clinical trials, serum transaminase elevations typically occurred in the first two monthsof treatment initiation; however, there were some cases observed up to 18 months after initiation of treatment,
particularly in patients taking concomitant valproate. Resolution of transaminase elevations occurred withdiscontinuation of EPIDIOLEX or reduction of EPIDIOLEX and/or concomitant valproate in about two-thirdsof the cases. In about one-third of the cases, transaminase elevations resolved during continued treatment withEPIDIOLEX, without dose reduction.

In the postmarketing setting, cases of cholestatic or mixed patterns of liver injury (i.e., based on calculated ratioof [ALT/ULN]/[ALP/ULN] less than 2 and between 2-5, respectively) were reported in patients treated withEPIDIOLEX.
Risk Factors for Transaminase Elevation
Concomitant Valproate and Clobazam
The majority of ALT elevations in the controlled studies occurred in patients taking concomitant valproate [seeDrug Interactions (7.3)]. Concomitant use of clobazam also increased the incidence of transaminase elevations,although to a lesser extent than valproate [see Drug Interactions (7.2)]. In EPIDIOLEX-treated patients with
LGS or DS (10 and 20 mg/kg/day dosages), the incidence of ALT elevations greater than 3 times the ULN was
30% in patients taking both concomitant valproate and clobazam, 21% in patients taking concomitant valproate(without clobazam), 4% in patients taking concomitant clobazam (without valproate), and 3% in patients taking
neither drug. In EPIDIOLEX-treated patients with TSC (25 mg/kg/day), the incidence of ALT elevations
greater than 3 times the ULN was 20% in patients taking both concomitant valproate and clobazam, 25% inpatients taking concomitant valproate (without clobazam), 0% in patients taking concomitant clobazam (without
valproate), and 6% in patients taking neither drug.
Consider discontinuation or dose adjustment of valproate or clobazam if liver enzyme elevations occur.
In the postmarketing setting, cases of elevated ammonia levels were reported in some EPIDIOLEX-treatedpatients who also had transaminase elevations; where data were available, most cases reported concomitant useof valproate, clobazam, or both. Consider discontinuation or dose adjustment of valproate or clobazam if
ammonia level elevations occur.
Dose
Transaminase elevations are generally dose-related. In patients with DS or LGS (10 and 20 mg/kg/day) or TSC(25 mg/kg/day), ALT elevations greater than 3 times the ULN were reported in 17% and 12% of patients taking
EPIDIOLEX 20 or 25 mg/kg/day, respectively, compared with 1% in patients taking EPIDIOLEX 10
mg/kg/day. The risk of ALT elevations was higher (25%) in patients with TSC receiving a dosage above therecommended maintenance dosage of 25 mg/kg/day in Study 4.
Baseline Transaminase Elevations
Patients with baseline transaminase levels above the ULN had higher rates of transaminase elevations when
taking EPIDIOLEX. In the DS and LGS controlled trials (Studies 1, 2, and 3) in patients taking EPIDIOLEX
20 mg/kg/day, the frequency of treatment-emergent ALT elevations greater than 3 times the ULN was 30%
when ALT was above the ULN at baseline, compared to 12% when ALT was within the normal range atbaseline. No patients taking EPIDIOLEX 10 mg/kg/day experienced ALT elevations greater than 3 times the
ULN when ALT was above the ULN at baseline, compared with 2% of patients in whom ALT was within thenormal range at baseline. In the TSC controlled trial (Study 4) in patients taking EPIDIOLEX 25 mg/kg/day,the frequency of treatment-emergent ALT elevations greater than 3 and 5 times the ULN were both 11% when
ALT was above the ULN at baseline, compared to 12% and 6%, respectively, when ALT was within the normal
range at baseline.
Monitoring
In general, transaminase elevations of greater than 3 times the ULN in the presence of elevated bilirubin without
an alternative explanation are an important predictor of severe liver injury. Early identification of elevated liver
enzymes may decrease the risk of a serious outcome. Patients with elevated baseline transaminase levels above
3 times the ULN, accompanied by elevations in bilirubin above 2 times the ULN, should be evaluated prior toinitiation of EPIDIOLEX treatment.

Prior to starting treatment with EPIDIOLEX, obtain serum transaminases (ALT and AST) and total bilirubinlevels. Serum transaminases and total bilirubin levels should be obtained at 1 month, 3 months, and 6 months
after initiation of treatment with EPIDIOLEX, and periodically thereafter or as clinically indicated. Serumtransaminases and total bilirubin levels should also be obtained within 1 month following changes in
EPIDIOLEX dosage and addition of or changes in medications that are known to impact the liver. Consider
more frequent monitoring of serum transaminases and bilirubin in patients who are taking valproate or who
have elevated liver enzymes at baseline.
If a patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea,
vomiting, right upper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine), promptly
measure serum transaminases and total bilirubin and interrupt or discontinue treatment with EPIDIOLEX, asappropriate. Discontinue EPIDIOLEX in any patients with elevations of transaminase levels greater than
3 times the ULN and bilirubin levels greater than 2 times the ULN. Patients with sustained transaminase
elevations of greater than 5 times the ULN should also have treatment discontinued. Patients with prolonged
elevations of serum transaminases should be evaluated for other possible causes. Consider dosage adjustmentof any coadministered medication that is known to affect the liver (e.g., valproate and clobazam).
5.2 Somnolence and Sedation
EPIDIOLEX can cause somnolence and sedation. In controlled studies for LGS and DS (10 and 20 mg/kg/day
dosages), the incidence of somnolence and sedation (including lethargy) was 32% in EPIDIOLEX-treatedpatients (27% and 34% of patients taking EPIDIOLEX 10 or 20 mg/kg/day, respectively), compared with 11%
in patients on placebo and was generally dose-related. The rate was higher in patients on concomitant clobazam(46% in EPIDIOLEX-treated patients taking clobazam compared with 16% in EPIDIOLEX-treated patients not
on clobazam). In the controlled study for TSC, the incidence of somnolence and sedation (including lethargy)
was 19% in EPIDIOLEX-treated patients (25 mg/kg/day), compared with 17% in patients on placebo. The rate
was higher in patients on concomitant clobazam (33% in EPIDIOLEX-treated patients taking clobazam
compared with 14% in EPIDIOLEX-treated patients not on clobazam). In general, these effects were morecommon early in treatment and may diminish with continued treatment. Other CNS depressants, including
alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX. Prescribers should monitor
patients for somnolence and sedation and should advise patients not to drive or operate machinery until they
have gained sufficient experience on EPIDIOLEX to gauge whether it adversely affects their ability to drive or
operate machinery.
5.3 Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including EPIDIOLEX, increase the risk of suicidal thoughts or behavior inpatients taking these drugs for any indication. Patients treated with an AED for any indication should bemonitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes
in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs
showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk
1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In thesetrials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or
ideation among 27863 AED-treated patients was 0.43%, compared to 0.24% among 16029 placebo-treatedpatients, representing an increase of approximately one case of suicidal thinking or behavior for every 530
patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treatedpatients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting
drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included inthe analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could
not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The
finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggeststhat the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5−100
years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated
AEDs.
Table 2: Risk of Suicidal Thoughts or Behaviors by Indication for Antiepileptic Drugs in the Pooled
Analysis
Indication

Placebo Patientswith Events Per
1000 Patients

Drug Patientswith Events
Per 1000Patients

Relative Risk: Incidenceof Events in Drug
Patients/Incidence inPlacebo Patients

Risk Difference:
Additional Drug
Patients with Events
Per 1000 Patients

Epilepsy
Psychiatric
Other
Total

1.0
5.7
1.0
2.4

3.4
8.5
1.8
4.3

3.5
1.5
1.9
1.8

2.4
2.9
0.9
1.9

The relative risk for suicidal thoughts or behavior was higher in clinical trials in patients with epilepsy than inclinical trials in patients with psychiatric or other conditions, but the absolute risk differences were similar forthe epilepsy and psychiatric indications.
Anyone considering prescribing EPIDIOLEX or any other AED must balance the risk of suicidal thoughts or
behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed
are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.
Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these
symptoms in any given patient may be related to the illness being treated.
5.4 Hypersensitivity Reactions
EPIDIOLEX can cause hypersensitivity reactions. Some subjects in the EPIDIOLEX clinical trials had
pruritus, erythema, and angioedema requiring treatment, including corticosteroids and antihistamines. Patientswith known or suspected hypersensitivity to any ingredients of EPIDIOLEX were excluded from the clinical
trials. If a patient develops hypersensitivity reactions after treatment with EPIDIOLEX, the drug should be
discontinued. EPIDIOLEX is contraindicated in patients with a prior hypersensitivity reaction to cannabidiol or
any of the ingredients in the product, which includes sesame seed oil [see Description (11)].
5.5 Withdrawal of Antiepileptic Drugs (AEDs)
As with most antiepileptic drugs, EPIDIOLEX should generally be withdrawn gradually because of the risk ofincreased seizure frequency and status epilepticus [see Dosage and Administration (2.5) and Clinical Studies(14)]. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.
6 ADVERSE REACTIONS
The following important adverse reactions are described elsewhere in labeling:• Hepatic Injury [see Warnings and Precautions (5.1)]• Somnolence and Sedation [see Warnings and Precautions (5.2)]• Suicidal Behavior and Ideation [see Warnings and Precautions (5.3)]

• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]• Withdrawal of Antiepileptic Drugs [see Warnings and Precautions (5.5)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
In controlled and uncontrolled trials in patients with LGS and DS, 689 patients were treated with EPIDIOLEX,
including 533 patients treated for more than 6 months, and 391 patients treated for more than 1 year. In
controlled and uncontrolled trials in patients with TSC, 223 patients were treated with EPIDIOLEX, including
151 patients treated for more than 6 months, 88 patients treated for more than 1 year, and 15 patients treated formore than 2 years.
In an expanded access program and other compassionate use programs, 271 patients with DS, LGS, or TSC
were treated with EPIDIOLEX, including 237 patients treated for more than 6 months, 204 patients treated formore than 1 year, and 140 patients treated for more than 2 years.
Patients with LGS or DS
In placebo-controlled trials of patients with LGS or DS (includes Studies 1, 2, 3, and a Phase 2 controlled study
in DS), 323 patients received EPIDIOLEX [see Clinical Studies (14.1, 14.2)]. Adverse reactions are presented
below; the duration of treatment in these trials was up to 14 weeks. Approximately 46% of patients werefemale, 83% were Caucasian, and the mean age was 14 years (range 2 to 48 years). All patients were taking
other AEDs.
In controlled trials in LGS or DS, the rate of discontinuation as a result of any adverse reaction was 2.7% forpatients taking EPIDIOLEX 10 mg/kg/day, 11.8% for patients taking EPIDIOLEX 20 mg/kg/day, and 1.3% forpatients on placebo. The most frequent cause of discontinuations was transaminase elevation. Discontinuation
for transaminase elevation occurred at an incidence of 1.3% in patients taking EPIDIOLEX 10 mg/kg/day, 5.9%
in patients taking EPIDIOLEX 20 mg/kg/day, and 0.4% in patients on placebo. Somnolence, sedation, andlethargy led to discontinuation in 3% of patients taking EPIDIOLEX 20 mg/kg/day compared to 0% of patientstaking EPIDIOLEX 10 mg/kg/day or on placebo.
The most common adverse reactions that occurred in EPIDIOLEX-treated patients with LGS or DS (incidence
at least 10% and greater than placebo) were somnolence; decreased appetite; diarrhea; transaminase elevations;fatigue, malaise, and asthenia; rash; insomnia, sleep disorder, and poor quality sleep; and infections.
Table 3 lists the adverse reactions that were reported in at least 3% of EPIDIOLEX-treated patients, and at a
rate greater than those on placebo, in the placebo-controlled trials in LGS and DS.

Table 3: Adverse Reactions in Patients Treated with EPIDIOLEX in Controlled Trials of LGS and DS(Studies 1, 2, and 3)

Adverse Reactions
Hepatic Disorders
Transaminases elevated
Gastrointestinal Disorders
Decreased appetite
Diarrhea
Weight decreased
Gastroenteritis
Abdominal pain, discomfort
Nervous System Disorders
Somnolence
Fatigue, malaise, asthenia
Lethargy
Sedation
Irritability, agitation
Aggression, anger
Insomnia, sleep disorder, poor quality sleep
Drooling, salivary hypersecretion
Gait disturbanceInfections
Infection, all
Infection, other
Infection, viral
Pneumonia
Infection, fungal
Other
Rash
Hypoxia, respiratory failure

EPIDIOLEX
10 mg/kg/day
20 mg/kg/day
N=75
N=238
%
%

Placebo
N=227
%

8

16

3

16
9
3
0
3

22
20
5
4
3

5
9
1
1
1

23
11
4
3
9
3
11
1
3

25
12
8
6
5
5
5
4
2

8
4
2
1
2
<1
4
<1
<1

41
25
7
8
1

40
21
11
5
3

31
24
6
1
0

7
3

13
3

3
1

Adverse reactions were similar across LGS and DS in pediatric and adult patients.
Patients with TSC
In a placebo-controlled trial of patients with TSC (Study 4), 148 patients received EPIDIOLEX [see ClinicalStudies (14.3)]. Adverse reactions are presented below; the duration of treatment in this trial was up to 16
weeks. Approximately 42% of patients were female, 90% were Caucasian, and the mean age was 14 years(range 1 to 57 years). All patients but one (25 mg/kg/day group) were taking other AEDs.
In the controlled trial in TSC, the rate of discontinuation as a result of any adverse reaction was 11% forpatients taking EPIDIOLEX 25 mg/kg/day and 3% for patients on placebo. The most frequent cause of
discontinuation was rash (5%).
The most common adverse reactions that occurred in EPIDIOLEX-treated patients with TSC (incidence at least
10% at the recommended dosage and greater than placebo) were diarrhea; transaminase elevations; decreased
appetite; somnolence; pyrexia; and vomiting.

Table 4 lists the adverse reactions that were reported in at least 3% of EPIDIOLEX-treated patients, and at a
rate greater than those on placebo, in the placebo-controlled trial in TSC.
Table 4: Adverse Reactions in Patients Treated with EPIDIOLEX in Controlled Trial of TSC (Study 4)Adverse Reactions

Hematological changes
AnemiaPlatelet count decreased
Eosinophil count increased
Hepatic Disorders
Transaminases elevated
Gastrointestinal Disorders
Diarrhea
Decreased appetite
Vomiting
NauseaGastroenteritis
Weight decreased
Nervous System Disorders
Somnolence
Gait disturbance
Fatigue, malaise, asthenia
Infections
Ear infection
Urinary tract infection
Pneumonia
Other
Pyrexia
Rash
Rhinorrhea

EPIDIOLEX
25 mg/kg/day
N = 75%

Placebo

7
5
5

1
1
0

25

0

31
20
17
9
8
7

25
12
9
3
7
0

13
9
5

9
5
1

8
5
4

3
0
1

19
8
4

8
4
0

N = 76%Adverse reactions were similar in pediatric and adult patients with TSC.
Additional Adverse Reactions in Patients with LGS, DS, or TSC
Decreased Weight
EPIDIOLEX can cause weight loss. In the controlled trials of patients with LGS or DS (10 and 20 mg/kg/day),based on measured weights, 16% of EPIDIOLEX-treated patients had a decrease in weight of at least 5% fromtheir baseline weight, compared to 8% of patients on placebo. The decrease in weight appeared to be doserelated, with 18% of patients on EPIDIOLEX 20 mg/kg/day experiencing a decrease in weight at least 5%,compared to 9% in patients on EPIDIOLEX 10 mg/kg/day. In the controlled trial of patients with TSC (25mg/kg/day), 31% of EPIDIOLEX-treated patients had a decrease in weight of at least 5% from their baseline
weight, compared to 8% of patients on placebo. In some cases, the decreased weight was reported as anadverse event (see Tables 3 and 4).

Hematologic Abnormalities
EPIDIOLEX can cause decreases in hemoglobin and hematocrit. In controlled trials of patients with LGS or
DS, the mean decrease in hemoglobin from baseline to end of treatment was -0.42 g/dL in EPIDIOLEX-treatedpatients receiving 10 or 20 mg/kg/day and -0.03 g/dL in patients on placebo. A corresponding decrease inhematocrit was also observed, with a mean change of -1.5% in EPIDIOLEX-treated patients, and -0.4% in
patients on placebo. In the trial of patients with TSC, the mean decrease in hemoglobin from baseline to end oftreatment was -0.37 g/dL in EPIDIOLEX-treated patients receiving 25 mg/kg/day and 0.07 g/dL in patients onplacebo. A corresponding decrease in hematocrit was also observed, with a mean change of -1.2% in
EPIDIOLEX-treated patients, and -0.2% in patients on placebo.
There was no effect on red blood cell indices. Thirty percent (30%) of EPIDIOLEX-treated patients with LGS
and DS and 38% of EPIDIOLEX-treated patients with TSC developed a new laboratory-defined anemia during
the course of the study (defined as a normal hemoglobin concentration at baseline, with a reported value lessthan the lower limit of normal at a subsequent time point), versus 13% of patients with LGS and DS on placebo
and 15% of patients with TSC on placebo.
Increases in Creatinine
EPIDIOLEX can cause elevations in serum creatinine. The mechanism has not yet been determined. In
controlled studies in healthy adults and in patients with LGS, DS, and TSC, an increase in serum creatinine ofapproximately 10% was observed within 2 weeks of starting EPIDIOLEX. The increase was reversible inhealthy adults. Reversibility was not assessed in studies in LGS, DS, or TSC.
Increases in Pneumonia with Concomitant Clobazam
Pneumonia has been observed in controlled trials in patients with LGS and DS more frequently with clobazam(7 of 41 [17%] in patients receiving 10 mg/kg/day EPIDIOLEX, 13 of 125 [10%] in patients receiving
20 mg/kg/day EPIDIOLEX, and 1 of 123 [1%] receiving placebo) than without concomitant clobazam (0% inpatients receiving 10 mg/kg/day EPIDIOLEX, 4 of 113 [4%] in patients receiving 20 mg/kg/day EPIDIOLEX,
and 1 of 104 [1%] receiving placebo). In the controlled trial in patients with TSC, pneumonia was observed
more frequently with concomitant clobazam (3 of 18 [17%] in patients receiving 25 mg/kg/day EPIDIOLEX
and 0 of 25 [0%] receiving placebo) than without clobazam (0 of 57 [0%] in patients receiving 25 mg/kg/day
EPIDIOLEX and 1 of 51 [2%] receiving placebo).
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on EPIDIOLEX
Strong CYP3A4 or CYP2C19 Inducers
Coadministration with a strong CYP3A4 and CYP2C19 inducer (rifampin 600 mg once daily) decreased
cannabidiol and 7-OH-CBD plasma concentrations by approximately 32% and 63%. The impact of suchchanges on efficacy of EPIDIOLEX is not known [see Clinical Pharmacology (12.3)]. Consider an increase in
EPIDIOLEX dosage (based on clinical response and tolerability) up to 2-fold, when coadministered with astrong CYP3A4 and/or CYP2C19 inducer.
7.2 Effect of EPIDIOLEX on Other Drugs
UGT1A9, UGT2B7, CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 Substrates
Cannabidiol is a weak inhibitor of CYP1A2 [see Clinical Pharmacology (12.3)]. Increases in exposure ofsensitive CYP1A2 substrates (e.g., caffeine, theophylline, or tizanidine) may be observed when coadministeredwith cannabidiol.
In vitro data predict drug-drug interactions with CYP2B6 substrates (e.g., bupropion, efavirenz), uridine
5'-diphospho-glucuronosyltransferase 1A9 (UGT1A9) substrates (e.g., diflunisal, propofol, fenofibrate), andUGT2B7 substrates (e.g., gemfibrozil, lamotrigine, morphine, lorazepam) when coadministered withEPIDIOLEX. Coadministration of EPIDIOLEX is also predicted to cause clinically significant interactions
with CYP2C8 and CYP2C9 (e.g., phenytoin) substrates. Because of potential inhibition of enzyme activity,
consider a reduction in dosage of substrates of UGT1A9, UGT2B7, CYP1A2, CYP2C8, and CYP2C9, as
clinically appropriate, if adverse reactions are experienced when administered concomitantly with EPIDIOLEX.
Because of the potential for both induction and inhibition of enzyme activity, consider adjusting dosage ofsubstrates of CYP2B6, as clinically appropriate.
Sensitive CYP2C19 Substrates
In vivo data show that coadministration of EPIDIOLEX increases plasma concentrations of drugs that are
metabolized by (i.e., are substrates of) CYP2C19 (e.g., diazepam) and may increase the risk of adverse reactions
with these substrates [see Clinical Pharmacology (12.3)]. Consider a reduction in dosage of sensitive
CYP2C19 substrates, as clinically appropriate, when coadministered with EPIDIOLEX.
Clobazam
Coadministration of EPIDIOLEX produces a 3-fold increase in plasma concentrations ofN-desmethylclobazam, the active metabolite of clobazam (a substrate of CYP2C19), with no effect on clobazam
levels [see Clinical Pharmacology (12.3)]. The increase in N-desmethylclobazam may increase the risk ofclobazam-related adverse reactions [see Adverse Reactions (6.1) and Warnings and Precautions (5.1, 5.2)].
Consider a reduction in dosage of clobazam if adverse reactions known to occur with clobazam are experienced
when coadministered with EPIDIOLEX.
Stiripentol
Concomitant use of EPIDIOLEX and stiripentol causes an elevation in exposure to stiripentol [see ClinicalPharmacology (12.3)]. The mechanism of this interaction has not been determined. The clinical relevance of
this effect is unknown, but patients should be monitored for stiripentol-related adverse drug reactions.
Sensitive P-gp Substrates Given Orally
Coadministration of EPIDIOLEX with orally administered everolimus, a P-gp and CYP3A4 substrate, results in
an approximately 2.5-fold increase in mean Cmax and AUC of everolimus [see Clinical Pharmacology (12.3)].
When initiating EPIDIOLEX in patients taking everolimus, monitor therapeutic drug levels of everolimus andadjust the dosage accordingly. When initiating everolimus in patients taking a stable dosage of EPIDIOLEX, alower starting dose of everolimus is recommended, with therapeutic drug monitoring.
Increases in exposure of other orally administered P-gp substrates (e.g., sirolimus, tacrolimus, digoxin) may beobserved on coadministration with EPIDIOLEX. Therapeutic drug monitoring and dose reduction of other P-gp
substrates should be considered when given orally and concurrently with EPIDIOLEX.
7.3 Concomitant Use of EPIDIOLEX and Valproate
Concomitant use of EPIDIOLEX and valproate increases the incidence of liver enzyme elevations [seeWarnings and Precautions (5.1)]. If such elevations occur, discontinuation or reduction of EPIDIOLEX and/or
concomitant valproate should be considered. Insufficient data are available to assess the risk of concomitantadministration of other hepatotoxic drugs and EPIDIOLEX.
7.4 CNS Depressants and Alcohol
Concomitant use of EPIDIOLEX with other CNS depressants (including alcohol) may increase the risk ofsedation and somnolence [see Warnings and Precautions (5.2)].

8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
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:• EPIDIOLEX Pregnancy Surveillance Program
o 1-855-272-7158
o https://www.epidiolexpregnancystudy.com•

North American Antiepileptic Drug (NAAED) Pregnancy Registryo 1-888-233-2334
o https://www.aedpregnancyregistry.org/
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 oforganogenesis resulted in embryofetal mortality at the highest dose tested. There were no other drug-relatedmaternal or developmental effects. The highest no-effect dose for embryofetal toxicity in rats was associatedwith maternal plasma cannabidiol exposures (AUC) approximately 16 and 9 times that in humans at therecommended 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 levelfor 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 andlactation, decreased growth, delayed sexual maturation, neurobehavioral changes (decreased activity), andadverse effects on male reproductive organ development (small testes in adult offspring) and fertility wereobserved 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.
8.2 Lactation
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 thebreastfed infant from EPIDIOLEX or from the underlying maternal condition.
8.4 Pediatric Use
Safety and effectiveness of EPIDIOLEX for the treatment of seizures associated with LGS, DS, or TSC havebeen 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 byoral administration of 0, 100, 150, or 250 mg/kg on PNDs 7-77) to juvenile rats for 10 weeks resulted inincreased 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-effectdose 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.
8.5 Geriatric Use
Clinical trials of EPIDIOLEX in the treatment of LGS, DS, and TSC did not include a sufficient number ofpatients 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 concomitantdisease or other drug therapy [see Dosage and Administration (2.6), Warnings and Precautions (5.1), andClinical Pharmacology (12.3)].
8.6 Hepatic Impairment
Because of an increase in exposure to EPIDIOLEX, dosage adjustments are necessary in patients with moderateor severe hepatic impairment [see Dosage and Administration (2.6), Warnings and Precautions (5.1), andClinical Pharmacology (12.3)]. EPIDIOLEX does not require dosage adjustments in patients with mild hepatic
impairment.
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
EPIDIOLEX is not a controlled substance.
9.2 AbuseAnimal 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 humanabuse potential study, acute administration of cannabidiol to non-dependent adult recreational drug users attherapeutic 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 toplacebo 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.

9.3 Dependence
In a human physical dependence study, administration of cannabidiol 1500 mg/day (750 mg twice daily) toadults 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 physicaldependence.
11 DESCRIPTION
Cannabidiol is a cannabinoid designated chemically as 2-[(1R,6R)-3-Methyl-6-(1-methylethenyl)-2cyclohexen-1-yl]-5-pentyl-1,3-benzenediol (IUPAC/CAS). Its empirical formula is C21H30O2 and its molecularweight is 314.46. The chemical structure is:

Cannabidiol, the active ingredient in EPIDIOLEX, is a cannabinoid that naturally occurs in the Cannabis sativa
L. plant.
Cannabidiol is a white to pale yellow crystalline solid. It is insoluble in water and is soluble in organic solvents.
EPIDIOLEX (cannabidiol) oral solution is a clear, colorless to yellow liquid containing cannabidiol at aconcentration of 100 mg/mL. Inactive ingredients include dehydrated alcohol (7.9% w/v), sesame seed oil,strawberry flavor, and sucralose. EPIDIOLEX contains no ingredient made from a gluten-containing grain(wheat, barley, or rye).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The precise mechanisms by which EPIDIOLEX exerts its anticonvulsant effect in humans are unknown.
Cannabidiol does not appear to exert its anticonvulsant effects through interaction with cannabinoid receptors.
12.2 Pharmacodynamics
Cardiac Electrophysiology
Concentration-dependent QTc prolongation was observed for EPIDIOLEX. At exposures obtained whenadministered as monotherapy at recommended doses with a high fat meal, EPIDIOLEX did not prolong the
QTc interval greater than 10 msec.
Other factors such as food intake, certain concomitant medications (e.g., clobazam), and alcohol consumption
may increase the exposure of EPIDIOLEX and the potential effect on QTc prolongation in this scenario is notknown.
12.3 Pharmacokinetics
Cannabidiol demonstrated an increase in exposure that was less than dose-proportional over the range of 5 to
25 mg/kg/day in patients.

Absorption
Cannabidiol has a time to maximum plasma concentration (Tmax) of 2.5 to 5 hours at steady state (Css).
Effect of Food
Coadministration of EPIDIOLEX (750 or 1500 mg) with a high-fat/high-calorie meal increased Cmax by 5-fold,
AUC by 4-fold, and reduced the total variability, compared with the fasted state in healthy volunteers [seeDosage and Administration (2.4)]. Coadministration of EPIDIOLEX with a low-fat/low-calorie meal increased
Cmax and AUC by 4-fold and 3-fold, respectively. Furthermore, coadministration of EPIDIOLEX with bovine
milk increased exposure by approximately 3-fold for Cmax and 2.5-fold for AUC. Coadministration of
EPIDIOLEX with alcohol also caused increased exposure to cannabidiol, with 93% increased Cmax and 63%
greater AUC.
Distribution
The apparent volume of distribution in healthy volunteers was 20963 L to 42849 L. Protein binding of thecannabidiol and its metabolites was > 94% in vitro.
Elimination
The half-life of cannabidiol in plasma was 56 to 61 hours after twice-daily dosing for 7 days in healthy
volunteers. The plasma clearance of cannabidiol following a single EPIDIOLEX 1500 mg dose (approximately
equal to the 20 mg/kg/day dosage) is 1111 L/h.
Metabolism
Cannabidiol is metabolized in the liver and the gut (primarily in the liver) by CYP2C19 and CYP3A4 enzymes,
and UGT1A7, UGT1A9, and UGT2B7 isoforms.
After repeat dosing, the active metabolite of cannabidiol, 7-OH-CBD, has a 38% lower AUC than the parent
drug. The 7-OH-CBD metabolite is converted to 7-COOH-CBD, which has an approximately 40-fold higher
AUC than the parent drug. Based on preclinical models of seizure, the 7-OH-CBD metabolite is active;
however, the 7-COOH-CBD metabolite is not active.
Excretion
EPIDIOLEX is excreted in feces, with minor renal clearance.
Specific Populations
Patients with Hepatic Impairment
No effects on the exposures of cannabidiol or metabolite exposures were observed following administration of asingle dose of EPIDIOLEX 200 mg in patients with mild (Child-Pugh A) hepatic impairment. Patients withmoderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment had an approximately 2.5 to 5.2-foldhigher AUC, compared with healthy volunteers with normal hepatic function [see Dosage and Administration(2.6), Warnings and Precautions (5.1), Use in Specific Populations (8.6)].
Drug Interaction Studies
In Vitro Assessment of Drug Interactions
Drug Metabolizing Enzymes [see Drug Interactions (7.1, 7.2)]
Cannabidiol is a substrate for CYP3A4 and CYP2C19. Cannabidiol has the potential to inhibit CYP1A2,
CYP2B6, CYP2C8, CYP2C9, and CYP2C19 at clinically relevant concentrations.
Cannabidiol may induce or inhibit CYP2B6 at clinically relevant concentrations.
Cannabidiol inhibits uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes UGT1A9 and UGT2B7, butdoes not inhibit the UGT1A1, UGT1A3, UGT1A4, UGT1A6, or UGT2B17 isoforms.

Transporters
Cannabidiol and the cannabidiol metabolite, 7-OH-CBD, are not anticipated to interact with BCRP, BSEP,
MDR1/P-gp, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, OATP1B1, or OATP1B3. However, due tolimitations of the in vitro testing procedure, inhibition of P-gp mediated efflux by cannabidiol in the intestine
could not be excluded. In vivo data show that CBD can affect P-gp efflux activity in the intestine [see In Vivo
Assessment of Drug Interactions].
The cannabidiol metabolite, 7-COOH-CBD, is not a substrate of BCRP, OATP1B1, OATP1B3, or OCT1.
However, 7-COOH-CBD is a substrate for P-gp. 7-COOH-CBD is an inhibitor of transport mediated via BCRP
and BSEP at clinically relevant concentrations.
In Vivo Assessment of Drug Interactions
Drug Interaction Studies with AEDs
Clobazam and Valproate
The interaction potential with other AEDs (clobazam and valproate) was evaluated in dedicated clinical studies
following coadministration of EPIDIOLEX (750 mg twice daily in healthy volunteers and 20 mg/kg/day inpatients).
Coadministration with clobazam in healthy volunteers increased the cannabidiol active metabolite 7-OH-CBD
mean Cmax by 73% and AUC by 47%; and increased the clobazam active metabolite, N-desmethylclobazam,
Cmax and AUC by approximately 3-fold, with no effect on clobazam levels [see Drug Interactions (7.2)].
When EPIDIOLEX was coadministered with valproate in a healthy-volunteer trial, there was no effect on thesystemic exposure to valproate. In a separate study in epilepsy patients investigating the effect of EPIDIOLEX
on valproate exposure, there were decreases in both the plasma Cmax and AUC of valproate, which were notclinically relevant (approximately 17% and 21%, respectively), and a decrease in exposure of the putative
hepatotoxic metabolite of valproate, 2-propyl-4-pentanoic acid (approximately 28% and 33%, respectively).
In the healthy-volunteer trial, coadministration with valproate resulted in no clinically relevant changes in
exposure to cannabidiol or its major metabolites (cannabidiol Cmax decreased by 26%; 6-OH-CBD AUC
increased by 27%; 7-OH-CBD AUC increased by 22%; 7-COOH-CBD Cmax and AUC increased by 25% and32%, respectively).
Effect of EPIDIOLEX on Midazolam
Coadministration of EPIDIOLEX with midazolam (a sensitive CYP3A4 substrate) did not result in changes inplasma concentrations of midazolam compared to midazolam administered alone.
Effect of EPIDIOLEX on Stiripentol
When EPIDIOLEX was coadministered with stiripentol in a healthy volunteer trial, Cmax and AUC of stiripentol
increased 28% and 55%, respectively. In patients with epilepsy, Cmax and AUC of stiripentol increased 17%
and 30%, respectively [see Drug Interactions (7.2)].
Effect of EPIDIOLEX on Caffeine
In vivo data from steady-state dosing with cannabidiol (750 mg twice daily) when coadministered with a single
dose of caffeine (200 mg), a sensitive CYP1A2 substrate, showed increased caffeine exposure by 15% for Cmax
and 95% for AUC compared to when caffeine was administered alone [see Drug Interactions (7.2)].
Effect of CYP3A4 and CYP2C19 Inducers and Inhibitors Coadministered with EPIDIOLEX on Exposure to
Cannabidiol
Coadministration of EPIDIOLEX with potent inhibitors of CYP3A4 and CYP2C19 had the following effects on
exposure to cannabidiol and its metabolites. The potent CYP3A4 inhibitor, itraconazole, increased exposure by< 10% for cannabidiol and < 20% for 7-OH-CBD and 7-COOH-CBD for both AUC and Cmax. Although theeffects of the potent CYP2C19 inhibitor fluconazole were slightly more marked, they are still considered not to
be clinically meaningful (cannabidiol increased by 22% and 24% for AUC and Cmax, respectively; 7-OH-CBD
decreased by 28% and 41% for AUC and Cmax; 7-COOH-CBD decreased by 33% and 48% for AUC and Cmax).
Coadministration with the potent CYP3A4 and CYP2C19 inducing agent rifampin caused a decrease incannabidiol exposure of 32% and 34% for AUC and Cmax [see Drug Interactions (7.1)]. There were moderatechanges in exposure to the active metabolite (7-OH-CBD decreased by 63% and 67% for AUC and Cmax,
7-COOH-CBD decreased by 48% for AUC, whereas there was no change in Cmax).
Effect of EPIDIOLEX on Everolimus
Coadministration of EPIDIOLEX (12.5 mg/kg twice daily) with the P-gp and CYP3A4 substrate everolimus(5 mg) in healthy volunteers led to an approximately 2.5-fold increase in everolimus mean Cmax and AUC [seeDrug Interactions (7.2)].
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis and Mutagenesis
Carcinogenesis
In a carcinogenicity study in mice, oral administration of cannabidiol (0 [water], 0 [vehicle], 30, 100, or
300 mg/kg/day) for 2 years resulted in an increased incidence of hepatocellular adenomas in male mice at thehighest dose tested. At the mid dose (100 mg/kg/day), plasma exposures (AUC) were approximately 5 and 3
times that at the recommended human doses (RHDs) of 20 and 25 mg/kg/day, respectively.
The carcinogenic potential of cannabidiol has not been assessed in rats.
Mutagenesis
Cannabidiol was negative for genotoxicity in in vitro (Ames) and in vivo (rat Comet and bone marrow
micronucleus) assays.
Impairment of Fertility
Oral administration of cannabidiol (0, 75, 150, or 250 mg/kg/day) to male and female rats, prior to andthroughout mating and continuing in females during early gestation, produced no adverse effects on fertility.
The highest dose tested was associated with plasma exposures (AUC) approximately 60 and 34 times that inhumans at the RHDs of 20 and 25 mg/kg/day, respectively.
14 CLINICAL STUDIES
14.1 Lennox–Gastaut Syndrome
The effectiveness of EPIDIOLEX for the treatment of seizures associated with LGS was established in two
randomized, double-blind, placebo-controlled trials in patients aged 2 to 55 years (Study 1, NCT02224690; andStudy 2, NCT02224560).
Study 1 (N=171) compared a dose of EPIDIOLEX 20 mg/kg/day with placebo. Study 2 (N=225) compared a
10 mg/kg/day dose and a 20 mg/kg/day dose of EPIDIOLEX with placebo. In both studies, patients had adiagnosis of LGS and were inadequately controlled on at least one AED, with or without vagal nerve
stimulation and/or ketogenic diet. Both trials had a 4-week baseline period, during which patients were required
to have a minimum of 8 drop seizures (≥ 2 drop seizures per week). The baseline period was followed by a 2week titration period and a 12-week maintenance period.
In Study 1, 94% of patients were taking at least 2 concomitant AEDs. The most frequently used concomitant
AEDs (greater than 25%) in Study 1 were clobazam (49%), valproate (40%), lamotrigine (37%), levetiracetam

(34%), and rufinamide (27%). In Study 2, 94% of patients were taking at least 2 concomitant AEDs. The mostfrequently used concomitant AEDs (greater than 25%) in Study 2, were clobazam (49%), valproate (38%),
levetiracetam (31%), lamotrigine (30%), and rufinamide (29%).
The primary efficacy measure in both studies was the percent change from baseline in the frequency (per28 days) of drop seizures (atonic, tonic, or tonic-clonic seizures) over the 14-week treatment period. Key
secondary endpoints in both studies included analyses of change in total seizure frequency and changes frombaseline in the Subject/Caregiver Global Impression of Change (S/CGIC) score at the last visit. For the
S/CGIC, the following question was rated on a 7-point scale: “Since [you/your child] started treatment, pleaseassess the status of [your/your child’s] overall condition (comparing [your/their] condition now to [your/their]
condition before treatment) using the scale below.” The 7-point scale was as follows: “Very Much Improved”(1); “Much Improved” (2); “Slightly Improved” (3); “No Change” (4); “Slightly Worse” (5); “Much Worse”(6); “Very Much Worse” (7).
In Studies 1 and 2, the median percent change from baseline (reduction) in the frequency of drop seizures was
significantly greater for both dosage groups of EPIDIOLEX than for placebo (Table 5). A reduction in drop
seizures was observed within 4 weeks of initiating treatment with EPIDIOLEX, and the effect remained
generally consistent over the 14-week treatment period.
Table 5: Change in Drop Seizure Frequency in Lennox–Gastaut Syndrome during the Treatment Period(Studies 1 and 2)
Drop Seizure Frequency(per 28 Days)

PlaceboEPIDIOLEX
10 mg/kg/day

EPIDIOLEX
20 mg/kg/day

Study 1

N=85

—

N=86

Baseline Period Median
Seizure Frequency

75

—

71

Median Percentage Change
from Baseline During
Treatment

−22

—

−44

p-value compared to placeboa
Study 2

N=76

N=73

N=76

Baseline Period Median
Seizure Frequency

80

87

86

Median Percentage Change
from Baseline During
Treatment

−17

−37

−42

<0.01

<0.01

p-value compared to placeboaa0.01

Obtained from a Wilcoxon rank-sum test.

Figure 1 displays the percentage of patients by category of reduction from baseline in drop seizure frequency
per 28 days during the treatment period in Study 1.

Figure 1: Proportion of Patients by Category of Seizure Response for EPIDIOLEX and Placebo inPatients with Lennox–Gastaut Syndrome (Study 1)

Figure 2 displays the percentage of patients by category of reduction from baseline in drop seizure frequency(per 28 days) during the treatment period in Study 2.
Figure 2: Proportion of Patients by Category of Seizure Response for EPIDIOLEX and Placebo inPatients with Lennox–Gastaut Syndrome (Study 2)

In Study 1, 3 of 85 (4%) patients in the EPIDIOLEX 20 mg/kg/day group reported no drop seizures during themaintenance period, compared to 0 patients in the placebo group. In Study 2, 3 of 73 (4%) patients in the
EPIDIOLEX 10 mg/kg/day group, 5 of 76 (7%) patients in the EPIDIOLEX 20 mg/kg/day group, and 1 of 76(1%) patients in the placebo group reported no drop seizures during the maintenance period.
In LGS patients, EPIDIOLEX was associated with significant reductions in total seizure frequency (drop andnon-drop seizures) versus placebo. During the treatment period in Study 1, the median percent reduction in
total seizure frequency (per 28 days) was 41% in patients taking EPIDIOLEX 20 mg/kg/day compared to 14%
in patients taking placebo (p<0.01). In Study 2, the median percent reduction in total seizure frequency (per 28days) was 36% in the 10 mg/kg/day group, 38% in the 20 mg/kg/day group, and 18% in the placebo group(p<0.01 for both groups).
A greater improvement on the Subject/Caregiver Global Impression of Change (S/CGIC) was reported inpatients treated with EPIDIOLEX compared with placebo in Studies 1 and 2. In Study 1, the mean S/CGIC
score at last visit was 3.0 in the 20 mg/kg/day EPIDIOLEX group (corresponding to “slightly improved”)
compared with 3.7 (most closely associated with “no change”) in the placebo group (p<0.01). In Study 2, themean S/CGIC score at last visit was 3.0 and 3.2 in the 10 mg/kg/day and 20 mg/kg/day EPIDIOLEX groups,
respectively (“slightly improved”), compared with 3.6 (“no change”) in the placebo group (p<0.01 and p=0.04,
respectively).
14.2 Dravet Syndrome
The effectiveness of EPIDIOLEX for the treatment of seizures associated with DS was demonstrated in a single
randomized, double-blind, placebo-controlled trial in 120 patients aged 2 to 18 years (Study 3, NCT02091375).
Study 3 compared a dose of EPIDIOLEX 20 mg/kg/day with placebo. Patients had a diagnosis of treatmentresistant DS and were inadequately controlled with at least one concomitant AED, with or without vagal nerve
stimulation or ketogenic diet. During the 4-week baseline period, patients were required to have at least
4 convulsive seizures while on stable AED therapy. The baseline period was followed by a 2-week titration
period and a 12-week maintenance period. The primary efficacy measure was the percent change from baselinein the frequency (per 28 days) of convulsive seizures (all countable atonic, tonic, clonic, and tonic-clonicseizures) over the 14-week treatment period.
In Study 3, 93% of patients were taking at least 2 concomitant AEDs during the trial. The most commonly usedconcomitant AEDs (greater than 25%) in Study 3 were clobazam (65%), valproate (57%), stiripentol (43%),
levetiracetam (28%), and topiramate (26%).
The median percent change from baseline (reduction) in the frequency of convulsive seizures was significantly
greater for EPIDIOLEX 20 mg/kg/day than for placebo (Table 6). A reduction in convulsive seizures wasobserved within 4 weeks of initiating treatment with EPIDIOLEX and the effect remained generally consistentover the 14-week treatment period.

Table 6: Change in Convulsive Seizure Frequency in Dravet Syndrome during the Treatment Period(Study 3)
Total Convulsive Seizures(per 28 Days)

PlaceboEPIDIOLEX
20 mg/kg/day

Study 3

N=59

N=61

Baseline Period Median
Seizure Frequency

15

12Median Percentage Change
from Baseline During
Treatment

−13

−39

p-value compared to placeboaa0.01

Obtained from a Wilcoxon rank-sum test.

Figure 3 displays the percentage of patients by category of reduction from baseline in convulsive seizure
frequency (per 28 days) during the treatment period in Study 3.
Figure 3: Proportion of Patients by Category of Seizure Response for EPIDIOLEX and Placebo inPatients with Dravet Syndrome (Study 3)

In Study 3, 4 of 60 (7%) patients treated with EPIDIOLEX 20 mg/kg/day reported no convulsive seizures
during the maintenance period, compared to 0 patients in the placebo group.

14.3 Tuberous Sclerosis Complex
The effectiveness of EPIDIOLEX for the treatment of seizures associated with TSC was demonstrated in arandomized, double-blind, placebo-controlled trial in 224 patients aged 1 to 65 years (Study 4; NCT02544763).
Study 4 (N=224) compared doses of EPIDIOLEX 25 mg/kg/day and 50 mg/kg/day (2 times the recommended
maintenance dosage) with placebo. Patients had a diagnosis of TSC and seizures inadequately controlled withat least one concomitant AED, with or without vagal nerve stimulation or ketogenic diet. During the 4-weekbaseline period, patients had at least 8 seizures, with at least 1 seizure occurring in at least 3 of the 4 weeks(focal motor seizures without impairment of consciousness or awareness; focal seizures with impairment ofconsciousness or awareness; focal seizures evolving to bilateral generalized convulsive seizures and generalized
seizures [tonic–clonic, tonic, clonic or atonic seizures]). The baseline period was followed by a 4-week titration
period and a 12-week maintenance period.
In Study 4, all patients but 1 (in EPIDIOLEX 25 mg/kg/day group) were taking 1-5 concomitant AEDs during
the trial. The most commonly used concomitant AEDs (greater than 25%) were valproate (45%), vigabatrin(33%), levetiracetam (29%), and clobazam (27%). The baseline median TSC-associated seizure frequency was
57 per 28 days for the combined groups. The primary efficacy measure was the change in seizure frequency of
TSC-associated seizures over the 16-week treatment period compared with baseline.
In Study 4, the percentage change from baseline (reduction) in the frequency of TSC-associated seizures was
significantly greater for patients treated with EPIDIOLEX than for placebo (Table 7). A reduction in TSCassociated seizures was observed within 4 weeks of initiating treatment with EPIDIOLEX and the effectremained generally consistent over the 12-week maintenance period.
Table 7: Change in TSC-Associated Seizure Frequency during the Treatment Period (Study 4)
Total TSC-Associated Seizures(per 28 Days)

PlaceboEPIDIOLEX
25 mg/kg/day

Study 4

N=76

N=75

Baseline Period Median Seizure
Frequency

54

56

Median Percentage Change fromBaseline During Treatment

−20

−43

p-value compared to placeboa
Percentage Change from Baseline
During Treatment in EstimatedMean Seizure Frequencyb
p-value compared to placebobaObtained from a Wilcoxon rank-sum test.
Obtained from a log-transformed ANCOVA.

b

<0.01
−24

−48

<0.01

Figure 4 displays the percentage of patients by category of reduction from baseline in TSC-associated seizure
frequency (per 28 days) during the treatment period in Study 4.
Figure 4: Proportion of Patients by Category of Seizure Response for EPIDIOLEX and Placebo inPatients with Tuberous Sclerosis Complex (Study 4)

In Study 4, 4 of 71 (6%) patients treated with EPIDIOLEX 25 mg/kg/day reported no TSC-associated seizures
during the maintenance period, compared to 0 patients in the placebo group.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
EPIDIOLEX is a strawberry-flavored, clear, colorless to yellow solution supplied in an amber glass bottle witha child-resistant closure. EPIDIOLEX is available in bottles containing 60 mL (NDC 70127-100-06) or 100 mLof 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).
16.2 Storage and HandlingStore 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.

17 PATIENT COUNSELING INFORMATION
Advise the caregiver or patient to read the FDA-approved patient labeling (Medication Guide and Instructions
for Use).
Administration Information
Advise patients who are prescribed EPIDIOLEX to use the adapter and oral dosing syringes provided [seeDosage and Administration (2.4) and Instructions for Use]. Provide instructions regarding which syringe to use
and how to administer the specified dose, since EPIDIOLEX is supplied with 1 mL and 5 mL oral dispensing
syringes.
Instruct patients to discard any unused EPIDIOLEX oral solution after 12 weeks of first opening the bottle [seeDosage and Administration (2.4)].
Hepatic Injury
Inform patients about the potential for elevations of liver enzymes. Discuss with the patient the importance ofmeasuring hepatic laboratory values and having them evaluated by the healthcare provider before treatment
with EPIDIOLEX and periodically during treatment [see Warnings and Precautions (5.1)]. Advise patients ofthe clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, rightupper quadrant abdominal pain, fatigue, anorexia, or jaundice and/or dark urine) and to contact a healthcare
provider promptly if these signs or symptoms occur.
Somnolence and Sedation
Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably
certain that EPIDIOLEX does not affect them adversely (e.g., impair judgment, thinking or motor skills) [seeWarnings and Precautions (5.2)].
Suicidal Thinking and Behavior
Counsel patients, their caregivers, and their families that antiepileptic drugs, including EPIDIOLEX, may
increase the risk of suicidal thoughts and behavior and advise them to be alert for the emergence or worseningof symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts,
behavior, or thoughts of self-harm. Instruct patients, caregivers, and families to report behaviors of concern
immediately to healthcare providers [see Warnings and Precautions (5.3)].
Withdrawal of Antiepileptic Drugs (AEDs)
Advise patients not to discontinue use of EPIDIOLEX without consulting with their healthcare provider.
EPIDIOLEX should normally be gradually withdrawn to reduce the potential for increased seizure frequency
and status epilepticus [see Dosage and Administration (2.5), Warnings and Precautions (5.5)].
Pregnancy Surveillance Program and Pregnancy Exposure Registry
Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during
EPIDIOLEX therapy. Encourage women who are taking EPIDIOLEX to enroll in both the EPIDIOLEX
Pregnancy Surveillance Program and the North American Antiepileptic Drug (NAAED) Pregnancy Registry ifthey become pregnant. The surveillance program and exposure registry are collecting information about thesafety of EPIDIOLEX and other antiepileptic drugs during pregnancy[see Use in Specific Populations (8.1)].
Drug Testing
Advise patients of the potential for positive cannabis drug screens.
Distributed by:
Jazz Pharmaceuticals, Inc.
Palo Alto, CA 94304
EPIDIOLEX® is a registered trademark of Jazz Pharmaceuticals plc or its subsidiaries.
© 2024 Jazz Pharmaceuticals, Inc.

MEDICATION GUIDEEPIDIOLEX® (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⚫ itching⚫ fever, feeling unwell, unusual tiredness⚫ unusual darkening of the urine⚫ yellowing of the skin or the whites of the eyes
⚫ right upper stomach area pain or discomfort(jaundice)
2. EPIDIOLEX may cause you to feel sleepy, which may get better over time. Using certain medicines withEPIDIOLEX such as clobazam or alcohol may increase sleepiness. Do not drive, operate heavy machinery, or doother 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 ofpeople, 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⚫ trouble sleeping (insomnia)⚫ attempt to commit suicide⚫ new or worse irritability⚫ new or worse depression⚫ acting aggressive, being angry, or violent⚫ new or worse anxiety⚫ acting on dangerous impulses⚫ feeling agitated or restless⚫ an extreme increase in activity and talking (mania)⚫ panic attacks⚫ other unusual changes in behavior or mood
How can I watch for early symptoms of suicidal thoughts and actions?
⚫ Pay attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings.
⚫ Keep all follow-up visits with your healthcare provider as scheduled.
4. Do not stop taking EPIDIOLEX without first talking to your healthcare provider. Stopping a seizure medicine suchas EPIDIOLEX suddenly can cause you to have seizures more often or seizures that do not stop (statusepilepticus).
Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
What is EPIDIOLEX?
⚫
EPIDIOLEX is a prescription medicine that is used to treat seizures associated with Lennox-Gastaut syndrome,
Dravet syndrome, or tuberous sclerosis complex in people 1 year of age and older.
⚫
It is not known if EPIDIOLEX is safe and effective in children under 1 year of age.
Who should not take EPIDIOLEX?
Do not take EPIDIOLEX if you are allergic to cannabidiol or any of the ingredients in EPIDIOLEX. See the end of thisMedication Guide for a complete list of ingredients in EPIDIOLEX.
Before taking EPIDIOLEX, tell your healthcare provider about all of your medical conditions, including if you:⚫
have or have had depression, mood problems or suicidal thoughts or behavior.
⚫
have liver problems.
⚫
have abused or been dependent on prescription medicines, street drugs or alcohol.
⚫
are pregnant or plan to become pregnant. Tell your healthcare provider right away if you become pregnant
while taking EPIDIOLEX. You and your healthcare provider will decide if you should take EPIDIOLEX while
you are pregnant. If you become pregnant while taking EPIDIOLEX, talk to your healthcare provider about
registering for both the EPIDIOLEX Pregnancy Surveillance Program and the North American Antiepileptic
Drug (NAAED) registry. The purpose of the surveillance program and exposure registry is to collect information
about the safety of EPIDIOLEX and other antiepileptic drugs during pregnancy.
o You can enroll in the EPIDIOLEX Pregnancy Surveillance Program by calling the toll free number 1855-272-7158 or visiting https://www.epidiolexpregnancystudy.com.
o You can enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll freenumber 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org.

are breastfeeding or plan to breastfeed. It is not known if EPIDIOLEX passes into your breast milk. Talk to
your healthcare provider about the best way to feed your baby while taking EPIDIOLEX.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter
medicines, vitamins, herbal supplements, and any cannabis-based products.
EPIDIOLEX may affect the way other medicines work, and other medicines may affect how EPIDIOLEX works. Do notstart or stop taking other medicines without talking to your healthcare provider. Know the medicines you take. Keep alist of them to show your healthcare provider and pharmacist when you get a new medicine.
Tell your healthcare provider if you are planning to have a cannabis drug screen because EPIDIOLEX may affectyour test results. Tell the person giving the drug test that you are taking EPIDIOLEX.
How should I take EPIDIOLEX?
⚫
Read the Instructions for Use at the end of this Medication Guide for information on the right way to use
EPIDIOLEX.
⚫
Take EPIDIOLEX exactly as your healthcare provider tells you.
⚫
Your healthcare provider will tell you how much EPIDIOLEX to take and when to take it.
⚫
Measure each dose of EPIDIOLEX using the bottle adapter and the appropriate dosing syringes that come withEPIDIOLEX. If your dose of EPIDIOLEX is 1 mL or less, use the 1 mL syringes to take your medicine.
⚫
Use a dry syringe each time you take EPIDIOLEX. If water is inside the syringe, it could cause the oil-based
medicine to look cloudy.
What should I avoid while taking EPIDIOLEX?
⚫
Do not drive, operate heavy machinery, or do other dangerous activities until you know how EPIDIOLEX affects
you. EPIDIOLEX may cause you to feel sleepy.
What are the possible side effects of EPIDIOLEX?
EPIDIOLEX can cause serious side effects, including:⚫
See “What is the most important information I should know about EPIDIOLEX?”
The most common side effects of EPIDIOLEX include:⚫
sleepiness⚫
rash⚫
decreased appetite⚫
sleep problems⚫
diarrhea⚫
fever⚫
increase in liver enzymes⚫
vomiting⚫
feeling very tired and weak⚫
infections
These are not all of the possible side effects of EPIDIOLEX. For more information ask your healthcare provider or
pharmacist.
Tell your healthcare provider about any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also contact Jazz Pharmaceuticals at 1-800-520-5568.
How should I store EPIDIOLEX?
⚫
Store EPIDIOLEX at room temperature between 68ºF to 77ºF (20ºC to 25ºC).
⚫
Always store EPIDIOLEX in an upright position.
⚫
Do not freeze.
⚫
Keep the child-resistant cap tightly closed.
⚫
Use EPIDIOLEX within 12 weeks of first opening the bottle. Throw away (dispose of) any unused medicine after
12 weeks.
Keep EPIDIOLEX and all medicines out of the reach of children.
General Information about the safe and effective use of EPIDIOLEX.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use
EPIDIOLEX for a condition for which it was not prescribed. Do not give EPIDIOLEX to other people, even if they havethe same symptoms that you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about EPIDIOLEX that is written for healthprofessionals.
What are the ingredients in EPIDIOLEX?
Active ingredient: cannabidiol
Inactive ingredients: dehydrated alcohol, sesame seed oil, strawberry flavor, and sucralose
EPIDIOLEX does not contain gluten (wheat, barley or rye).
⚫

Distributed by:
Jazz Pharmaceuticals, Inc.
Palo Alto, CA 94304
For more information, go to www.EPIDIOLEX.com or call 1-800-520-5568.
EPIDIOLEX® is a registered trademark of Jazz Pharmaceuticals plc or its subsidiaries.
© 2024 Jazz Pharmaceuticals, Inc.
This Medication Guide has been approved by the U.S. Food and Drug Administration

Revised: 3/2024

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:• Follow your healthcare provider’s instructions for the dose of EPIDIOLEX to take or give.
• Ask your healthcare provider or pharmacist if you are not sure how to prepare, take, or give theprescribed dose of EPIDIOLEX.
• Always use the oral syringe provided with EPIDIOLEX to make sure you measure the right amount of
EPIDIOLEX.
• Do not use EPIDIOLEX after the expiration date on the package and each bottle.
• Use EPIDIOLEX within 12 weeks of first opening the bottle.
• After 12 weeks, safely throw away (dispose of) any EPIDIOLEX that has not been used.

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:• 1 syringe to take or give the dose of EPIDIOLEX

•

1 extra syringe (included as a spare if needed)

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
1. Remove the child-resistant cap by pushing down while turning the cap to the left (counter-clockwise).

2. Push the bottle adapter firmly into the bottle. Make sure the bottle adapter is fully inserted. If not
fully inserted, small parts such as the bottle adapter may become a choking hazard for children andpets.
Note: Do not remove the bottle adapter from the bottle after it is inserted.

Prepare The DoseYour healthcare provider will tell you how much EPIDIOLEX to take or give.
3. Use this table to measure the total dose of EPIDIOLEX to be given.
Dose

How to measure1 mL or lessMore than 1 mL and less than 5 mL
More than 5 mL

Use the 1 mL oral syringe 1 time
Use the 5 mL oral syringe 1 time
Use the 5 mL oral syringe more than 1 time

4. Push the plunger all the way down and insert the tip of the oral syringe fully into the bottle adapter.
With the oral syringe in place, turn the bottle upside down.

5. Slowly pull the plunger of the oral syringe to withdraw the dose of EPIDIOLEX needed. See Step 3
for how to measure the total dose of EPIDIOLEX.
Line up the end of the plunger with the marking for your dose of EPIDIOLEX.

What to do if you see air bubbles:
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.
6. When you have measured the correct dose of EPIDIOLEX, leave the oral syringe in the bottle
adapter and turn the bottle right side up.

7. Carefully remove the oral syringe from the bottle adapter.

Give EPIDIOLEX
8. Place the tip of the oral syringe against the inside of the cheek and gently push the plunger until all
the EPIDIOLEX in the syringe is given.

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 themedicine. 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 Up9. Screw the child-resistant cap back on the bottle tightly by turning the cap to the right (clockwise).

Do not remove the bottle adapter. The cap will fit over it.
10. Fill a cup with warm soapy water and clean the oral syringe by drawing water in and out of thesyringe using the plunger.

11. Remove the plunger from the barrel of the oral syringe and rinse both parts under tap water.

Do not wash the oral syringe in the dishwasher.
12. Shake off any extra water from the plunger and oral syringe barrel, and allow them to air dry until
next use.

Make sure the oral syringe is completely dry before the next use. If water is inside the syringe, it
could cause the oil-based medicine to look cloudy.
Do not throw away the oral syringe.
How should I store EPIDIOLEX?
• Store EPIDIOLEX at room temperature between 68°F to 77°F (20°C to 25°C).
• Always store EPIDIOLEX in an upright position.
• Do not freeze.
• Keep the child-resistant cap tightly closed.
• Use EPIDIOLEX within 12 weeks of first opening the bottle. Dispose of any unused EPIDIOLEX after
12 weeks.
• Keep EPIDIOLEX and all medicines out of the reach of children.
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:
A:

What if there are air bubbles in the oral syringe?
Push the liquid back into the bottle and repeat Step 5 until the air bubbles are gone.

Q:
A:

What should I do if the liquid in the bottle has turned cloudy?
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:
A:

What should I do if the oral syringe is not completely dry before use?
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