Sympazan

Approved Uses

Sympazan is a prescription medication indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS). It is approved for use in adults and pediatric patients who are 2 years of age or older.

Lennox-Gastaut syndrome is a severe form of epilepsy that typically begins in early childhood. It is characterized by multiple types of seizures and may be accompanied by developmental delays or behavioral problems. Sympazan is intended to be used as an adjunctive therapy, meaning it is prescribed to be taken alongside other antiseizure medications rather than as a standalone treatment.

While Sympazan helps to control and reduce the frequency of seizures associated with LGS, it is not a cure for the condition. It belongs to a class of medications known as benzodiazepines.

Mechanism of Action

Sympazan belongs to a class of drugs known as benzodiazepines. It is primarily used to help control seizures by slowing down excessive activity in the central nervous system.

The medication works by increasing the effectiveness of gamma-aminobutyric acid (GABA), which is a neurotransmitter. Neurotransmitters are chemicals that nerve cells use to communicate with each other. GABA specifically acts as an inhibitory messenger, meaning it helps to block or inhibit certain brain signals and decrease activity in the nervous system.

By enhancing GABA, Sympazan helps to:

• Calm nerve cell activity: It makes the brain's nerve cells less sensitive to stimulation.
• Reduce electrical bursts: It helps prevent the sudden, excessive electrical discharges in the brain that cause seizures.

While the exact way it works for all seizure types is not completely understood, its ability to strengthen the brain's natural inhibitory signals is the main way it helps manage symptoms of Lennox-Gastaut syndrome.

Common Side Effects

The most frequently reported side effects of Sympazan include:

• Drowsiness or sedation
• Dizziness
• Problems with coordination or balance
• Constipation
• Drooling
• Vomiting
• Cough
• Tiredness
• Painful urination

Serious Side Effects

Seek medical attention immediately if you notice any of the following serious symptoms:

• Severe Skin Reactions: A rash that blisters or peels, which may indicate Stevens-Johnson syndrome or toxic epidermal necrolysis.
• DRESS Syndrome: A reaction involving fever, rash, and swollen lymph nodes that can affect the liver or other organs.
• Breathing Issues: Slow or shallow breathing, particularly when combined with opioid medications or alcohol.
• Mental Health Changes: Suicidal thoughts or actions, new or worsening depression, or unusual changes in mood or behavior.
• Extreme Sleepiness: Sedation so severe that it is difficult to wake the person.

Boxed Warnings

Sympazan includes boxed warnings for the following serious risks:

• Interactions with Opioids: Using this medication with opioid pain or cough medicines can cause severe drowsiness, breathing problems, coma, and death.
• Abuse and Addiction: As a benzodiazepine, Sympazan carries a risk of misuse and addiction. Misuse increases the risk of overdose and death.
• Dependence and Withdrawal: Stopping this medication suddenly or reducing the dose too quickly can cause life-threatening withdrawal symptoms, including seizures that do not stop, hallucinations, and tremors.

Serious Skin Reactions

Rare but life-threatening skin reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), can occur at any time during treatment. These reactions require immediate medical attention if a rash or skin peeling develops.

Suicidal Thoughts and Behavior

Antiepileptic drugs, including Sympazan, may increase the risk of suicidal thoughts or behaviors. Changes in mood, worsening depression, or unusual behavior should be monitored closely by healthcare providers and caregivers.

Somnolence and Sedation

This medication commonly causes sleepiness and decreased alertness. These effects are more likely when starting the drug or increasing the dose. It may impair the ability to drive or operate heavy machinery, especially when combined with alcohol or other drugs that cause drowsiness.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

A serious, potentially fatal multi-organ hypersensitivity reaction called DRESS has been reported with the use of this medication. Symptoms may include fever, rash, and swelling of the lymph nodes, and it can affect internal organs like the liver or kidneys.

Respiratory Depression

Sympazan may cause slowed or shallow breathing, particularly when used at high doses or in combination with other central nervous system depressants.

Pregnancy Considerations

Sympazan may cause harm to an unborn baby. Research suggests that using this medication during pregnancy can increase the risk of birth defects. If taken during the third trimester, it may lead to neonatal withdrawal symptoms or symptoms sometimes called floppy infant syndrome, which involves breathing difficulties, muscle weakness, and feeding problems in the newborn.

It is important not to start or stop taking seizure medication during pregnancy without medical guidance. Stopping the medication abruptly can cause breakthrough seizures that may harm both the pregnant person and the fetus. Patients are encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry to help track the safety of these medications.

Breastfeeding Considerations

Clobazam, the active ingredient in Sympazan, passes into breast milk. This may cause the nursing infant to experience side effects such as:

• Excessive sedation or sleepiness
• Difficulty feeding
• Low energy or poor weight gain

Decisions regarding breastfeeding while taking Sympazan should be made in consultation with a healthcare provider to weigh the benefits of breastfeeding against the potential risks to the infant.

Dosage Forms

Sympazan is supplied as an oral soluble film. This delivery method allows the medication to be administered by placing it on the tongue, where it dissolves.

• Oral Soluble Film: A thin, rectangular film intended for oral use.

Each film is individually packaged in a sealed pouch. The medication should be taken by placing the film on top of the tongue until it is completely dissolved. It can be taken with or without food, and water is not required for administration.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) approved Sympazan (clobazam) oral film in November 2018. It is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.

Regulatory Classification

Sympazan is classified as a Schedule IV controlled substance because it has a potential for abuse and may lead to physical or psychological dependence.

Boxed Warnings

The FDA-approved labeling for Sympazan includes boxed warnings regarding the following risks:

• Risks from Concomitant Use with Opioids: Using benzodiazepines like Sympazan with opioid medications may result in profound sedation, respiratory depression, coma, and death.
• Abuse, Misuse, and Addiction: The use of benzodiazepines exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death.
• Physical Dependence and Withdrawal Reactions: Continued use may lead to clinically significant physical dependence. Abruptly stopping or reducing the dosage rapidly can result in life-threatening withdrawal reactions.

Safety Communications

In 2023, the FDA issued a safety communication for several antiseizure medicines, including clobazam, regarding the risk of a rare but serious immune system reaction called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). This condition can be life-threatening and requires immediate medical attention if symptoms like fever, rash, or swollen lymph nodes occur.

Risks of Stopping Treatment

Sympazan is a benzodiazepine that can cause physical dependence, especially when used for a long time or at high doses. If you stop taking this medication abruptly or reduce the dose too quickly, you may experience withdrawal symptoms. In some cases, these symptoms can be life-threatening.

Withdrawal Symptoms

Common and serious withdrawal symptoms may include:

• Seizures that will not stop (status epilepticus)
• Hallucinations (seeing or hearing things that are not there)
• Tremors or shaking
• Nervousness, anxiety, or irritability
• Stomach and muscle cramps
• Sweating and vomiting
• Trouble sleeping

Because of these risks, you should never stop taking Sympazan or change your dose without consulting your healthcare provider. They will typically provide a schedule to gradually decrease the dose over several weeks or months to help prevent withdrawal reactions.