DIACOMIT®—developed specifically for Dravet syndrome1

Proven, effective seizure relief1,2

Dravet syndrome can be resistant to treatment, with multiple therapies and dosing adjustments often needed for adequate seizure control.3

DIACOMIT is a chemically unique antiepileptic drug developed through the Biocodex research program, approved for patients with Dravet syndrome age 2 and older as add-on therapy to clobazam when seizures are not adequately controlled.1,4 There are no clinical data to support the use of DIACOMIT as a monotherapy in Dravet syndrome.1

About DIACOMIT

DIACOMIT is a trusted, effective treatment that comes in 2 convenient dosing forms
DIACOMIT is a trusted, effective treatment that comes in 2 convenient dosing forms

The most common adverse reactions were somnolence, decreased appetite, agitation, ataxia, decreased weight, hypotonia, nausea, tremor, dysarthria, and insomnia.1

20 years of real-world use

DIACOMIT has 20 years of real-world use and has global approval for use
DIACOMIT has 20 years of real-world use and has global approval for use

An opportunity to significantly reduce seizure frequency1,2

Proven efficacy in pivotal studies1,2,16

DIACOMIT is the first antiepileptic drug to have clinically demonstrated efficacy in Dravet syndrome in 2 multicenter, double-blind, placebo-controlled, randomized trials.1,16 In these trials, patients with Dravet syndrome experienced significantly fewer seizures with DIACOMIT compared with placebo.2

Not an actual HCP

Efficacy: significant seizure reduction across 2 clinical trials2,*

DIACOMIT offers an opportunity to significantly reduce seizure frequency
DIACOMIT offers an opportunity to significantly reduce seizure frequency

In two clinical trials, 71% and 67% of patients responded to DIACOMIT1

43% and 25% of patients reported no generalized clonic or tonic-clonic seizures by the end of the second month of treatment1,7

Patient characteristics1:

  • 3 to <18 years of age§
  • Confirmed diagnosis of Dravet syndrome
  • Inadequately controlled on clobazam and valproate
  • Suffering from ≥4 generalized clonic or tonic-clonic seizures per month, despite optimized therapy

Primary endpoint1: responder rate

Secondary endpoint1: mean change from baseline in frequency of generalized clonic or tonic-clonic seizures

Study Design: The efficacy of DIACOMIT was established in two multicenter, randomized, double-blind, placebo-controlled studies conducted according to similar protocols. Patients and/or caregivers recorded the frequency of generalized clonic or tonic-clonic seizures during the study period.1

*STICLO France and STICLO Italy were multicenter, randomized, double-blind, placebo-controlled trials conducted according to similar protocols. The Italian study was performed after the French study and provided comparable results.1,2

Response was defined as experiencing a ≥50% decrease in the frequency of generalized clonic or tonic-clonic seizures during the treatment period compared with baseline.2,7

Seizure freedom was defined as experiencing no generalized clonic or tonic-clonic seizures for the duration of the study.1,6

§The effectiveness of DIACOMIT for the treatment of seizures associated with Dravet syndrome in patients 2 years of age to less than 3 years of age was extrapolated from the demonstration of effectiveness in patients 3 years to less than 18 years of age in STICLO France and STICLO Italy. Safety and effectiveness in pediatric patients under the age of 2 years have not been established.1,5

Mechanism of action

The mechanism by which DIACOMIT exerts its anticonvulsant effect in humans is unknown. Possible mechanisms of action include direct effects mediated through the gamma-aminobutyric acid (GABA)A receptor and indirect effects involving inhibition of cytochrome P450 activity with resulting increase in blood levels of clobazam and its active metabolite.1

Dosing and administration1

DIACOMIT is available in 250 mg and 500 mg dosages, in 2 convenient dosing forms: capsules and powder for oral suspension (fruit-flavored powder packets to be mixed in water).

DIACOMIT is available in 250 mg and 500 mg dosages, in 2 convenient dosing forms: capsules and powder for oral suspension (fruit-flavored powder packets to be mixed in water)
DIACOMIT is available in 250 mg and 500 mg dosages, in 2 convenient dosing forms: capsules and powder for oral suspension (fruit-flavored powder packets to be mixed in water)
DIACOMIT is available in 250 mg and 500 mg dosages, in 2 convenient dosing forms: capsules and powder for oral suspension (fruit-flavored powder packets to be mixed in water)

The recommended oral dosage of DIACOMIT is 50 mg/kg/day, divided into 2 or 3 separate doses, with a maximum total dosage of 3,000 mg/day.

The recommended oral dosage of DIACOMIT is 50 mg/kg/day, divided into 2 or 3 separate doses, with a maximum total dosage of 3,000 mg/day
The recommended oral dosage of DIACOMIT is 50 mg/kg/day, divided into 2 or 3 separate doses, with a maximum total dosage of 3,000 mg/day

In the event of a missed dose, DIACOMIT should be taken as soon as possible. If it is almost time for the next dose, patient should not take the missed dose. Doses should not be doubled.

Adverse reactions and patient management1

The most common adverse reactions, occurring in ≥10% of patients treated with DIACOMIT and more frequently than placebo, include:

  • Somnolence (67%)
  • Decreased appetite (45%)
  • Agitation (27%)
  • Ataxia (27%)
  • Decreased weight (27%)
  • Hypotonia (24%)
  • Nausea (15%)
  • Tremor (15%)
  • Dysarthria (12%)
  • Insomnia (12%)

Download the DIACOMIT Drug Interactions Card for more detailed information on potential interactions.

To report suspected adverse reactions, contact Biocodex at 1-866-330-3050 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Dravet syndrome

Disease characteristics and treatment

Dravet syndrome is a rare, lifelong epileptic syndrome that usually begins in the first year of life, when a normally developing infant presents with frequent, prolonged seizures.3,17-19 Because it is a spectrum disorder, patients present with a wide range of seizure types with varying responses to treatment.20 The primary goal of Dravet syndrome treatment is to reduce the frequency, length, and types of seizures.21

About Dravet syndrome

Dravet syndrome was first described in 1978 as severe myoclonic epilepsy in infancy (SMEI) by Dr. Charlotte Dravet.19

In the first year of life, seizures appear in an otherwise normally developing infant22

  • Generalized or unilateral clonic seizures, with or without fever22
  • These seizures may last more than 20 minutes and require emergency treatment (rectal or intravenous injection of an anticonvulsive)19,21

Between 2 and 3 years of age, other types of seizures develop23

  • Myoclonic seizures and partial (focal) seizures occur, accompanied by developmental regression or stagnation with behavior disorders18,22
  • Electroencephalograms (EEG) may remain nonspecific21

As it was discovered that not all of the original clinical signs were present in every patient, the diagnostic criteria were expanded.22

In 1989, the name of the epilepsy syndrome was changed from SMEI to its current name: Dravet syndrome.22

Dravet syndrome is estimated to appear in 1/15,700 births in the United States.24

Worldwide, Dravet syndrome seems to affect an equal number of boys and girls.24-27

Dravet syndrome diagnosis in toddlers and younger children*

For children suffering from seizures, understanding the underlying cause is important in selecting the right treatment for the patient. Earlier treatment could potentially contribute to better long-term outcomes.21

Initial presentation of Dravet syndrome includes21

  • Typical seizure onset between 1 and 18 months
  • Recurrent generalized tonic-clonic or hemiconvulsive seizures
  • Myoclonic seizures are typically seen by age 2 years. Obtundation status, focal dyscognitive seizures and atypical absences are also typical but usually occur after age 2 years. Typical absences and epileptic spasms are atypical
  • Hyperthermia, which may be associated with vaccination or illness, triggers seizures in the majority of patients; other triggers may include flashing lights, visual patterns, bathing, eating, and overexertion
  • Normal development and neurological examination at onset
  • Normal MRI and nonspecific EEG findings at onset

Because the patient’s initial brain scan may appear normal or their symptoms might present as a different form of epilepsy, many children with Dravet syndrome are misdiagnosed at first. For that reason, while not 100% conclusive, genetic testing is highly recommended.21

Genetic testing is available at no cost for children up to the age of 8, and for as little as $250 thereafter, through the Behind the Seizure® program at Invitae.com.

Genetic causes of Dravet syndrome:

  • Dravet syndrome is most often caused by a mutation in the SCN1A gene21
  • SCN1A is involved in transmitting signals between nerve cells28
  • The SCN1A mutation is seen in at least 75% of all Dravet syndrome patients21
  • Some patients will have a mutation in the gene and not have seizures; other patients might have seizures that look like Dravet syndrome without the mutation3
  • Around 5%-10% of cases are inherited, meaning that one of the parents will test positive for the same SCN1A gene mutation17
  • Infrequently, other genetic mutations may be associated with Dravet syndrome. There have been a number of other genes identified that are associated with Dravet syndrome: SCN2A, SCN8A, SCN1B, HCN1, GABRA1, GABRAG2, PCDH19, CHD2, STXBP1. Genes not yet identified may be involved as well3,29

*DIACOMIT is indicated for children 2 years of age and older.

Dravet syndrome presentation in older children, teens, and adults3,21

The symptoms of Dravet syndrome may change over time; however, the following characteristics may be seen in older children, teens, and adults:

  • Persisting seizures: focal and/or generalized convulsive seizures; often myoclonic, focal, atypical absence, and tonic seizures. Recurrent status epilepticus and obtundation status become less frequent, and may not be seen in teens and young adults
  • Hyperthermia as a seizure trigger may become less common
  • Seizure exacerbation may occur with the use of sodium channel blocking agents
  • Intellectual disability is evident by 18-60 months of age and persists into adulthood
  • Neurological exam abnormalities, which include ataxia, hypotonia, and impaired dexterity, are evident by age 3-4 years
  • An MRI is typically normal, but it may show mild generalized atrophy and/or hippocampal sclerosis
  • Genetic testing can still be helpful to confirm diagnosis
Navigating Life with Dravet Syndrome information booklet available to download

Patients and caregivers can download the Navigating Life with Dravet Syndrome booklet for useful information after a Dravet syndrome diagnosis.

Lifestyle support for patients with Dravet syndrome

Helping patients, caregivers, and families meet life’s challenges

Every family will have a different experience with Dravet syndrome, so it is important for them to recognize their child’s individual needs and to design a lifestyle around them. Creating routines, adhering to medication regimens, avoiding seizure triggers, and having regular communication with their HCPs are all ways to help families successfully manage Dravet syndrome.

Not actual patients

Living with Dravet syndrome

Dravet syndrome and its management have an impact on almost every aspect of life, complicating simple daily activities and making it difficult to make spontaneous plans.

Download the Navigating Life with Dravet Syndrome booklet to provide useful information for patients and their families.

After diagnosis, patients and caregivers should be given information on30

  • Genetic counseling and reproductive implications
  • Medication management
  • Ways to reduce exposure to seizure triggers
  • Seizure and trigger tracking
  • How to respond to seizure emergencies
  • The risk of SUDEP and seizure-related accidents
  • Developmental outcomes and expectations
  • Dietary and other supportive treatments
  • Care resources and local support groups
  • Educational support

Guidance and support

Resources for patients and caregivers

Direct caregivers to take advantage of the expanding collection of resources. Families can read about Dravet syndrome, discover new ways of helping their child navigate life, or find support groups to connect with other families affected by Dravet syndrome.

Building a support system

Managing a rare disease like Dravet syndrome can cause caregivers and families to feel lonely and isolated. Seeking support and community from friends, family, or other caregivers can help when times are difficult or when they need a reminder of their successes.

INDICATION and IMPORTANT SAFETY INFORMATION

INDICATION

DIACOMIT (stiripentol) capsules for oral use or powder for oral suspension are indicated for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older taking clobazam.

There are no clinical data to support the use of DIACOMIT as monotherapy in Dravet syndrome.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

No contraindications are listed.

WARNINGS & PRECAUTIONS

Somnolence

DIACOMIT can cause somnolence. Monitor patients for somnolence, particularly when DIACOMIT is used concomitantly with other CNS depressants or clobazam, which is also known to cause somnolence.

Decreased Appetite and Decreased Weight

DIACOMIT can cause decreases in appetite and weight. The growth and weight of pediatric patients treated with DIACOMIT should be carefully monitored.

Neutropenia and Thrombocytopenia

DIACOMIT can cause significant declines in neutrophil and platelet counts. Hematologic testing should be obtained prior to starting treatment with DIACOMIT and then every 6 months.

Withdrawal Symptoms

As with most antiepileptic drugs (AEDs), DIACOMIT should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus.

Risks in Patients with Phenylketonuria (PKU)

DIACOMIT powder for suspension contains phenylalanine, which can be harmful to patients with PKU. Before prescribing DIACOMIT powder for suspension to a patient with PKU, consider the total daily intake of phenylalanine from all sources, including DIACOMIT powder for suspension. DIACOMIT capsules do not contain phenylalanine.

Suicidal Behavior and Ideation

AEDs, including DIACOMIT, increase the risk of suicidal thoughts or behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

ADVERSE REACTIONS

The most common adverse reactions that occurred in at least 10% of DIACOMIT-treated patients and more frequently than on placebo were somnolence, decreased appetite, agitation, ataxia, decreased weight, hypotonia, nausea, tremor, dysarthria, and insomnia.

PREGNANCY

There are no adequate data on the developmental risks associated with the use of DIACOMIT in pregnant women. Based on animal data, DIACOMIT may cause fetal harm.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as DIACOMIT, during pregnancy. Physicians are advised to recommend that pregnant patients taking DIACOMIT enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (information at www.aedpregnancyregistry.org). This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves or their caregiver.

To report suspected adverse reactions, contact BIOCODEX at 1-866-330-3050 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full prescribing information for DIACOMIT®.

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