Onfi

Approved Uses

Onfi is used as an add-on treatment for seizures associated with Lennox-Gastaut syndrome (LGS). It is intended to be taken in combination with other anti-seizure medications to help improve seizure control.

Patient Population

This medication is approved for use in adults and children who are 2 years of age and older.

Conditions Treated

Lennox-Gastaut syndrome is a severe form of epilepsy that typically begins in early childhood. It is characterized by various types of seizures that can be difficult to manage. Onfi is a type of medication known as a benzodiazepine, which is used to help reduce the frequency of these seizures when used alongside other therapies.

Mechanism of Action

Onfi belongs to a class of medications known as benzodiazepines. While the exact way it works to treat seizures is not fully understood, it is believed to interact with specific receptors in the central nervous system to regulate brain activity.

The medication enhances the activity of a natural chemical in the brain called gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter, which means its primary role is to slow down or block certain signals in the nervous system. By increasing the effects of GABA, Onfi helps to:

• Reduce the excessive electrical activity that leads to seizures.
• Produce a calming effect on the central nervous system.
• Stabilize nerve cell signals to prevent them from firing uncontrollably.

By modulating these chemical signals, Onfi helps to decrease the frequency and severity of seizures, particularly those associated with Lennox-Gastaut syndrome.

Common Side Effects

Many people using Onfi experience mild side effects. These may include:

• Drowsiness or feeling very tired
• Dizziness
• Drooling
• Constipation
• Cough
• Pain when urinating
• Fever
• Difficulty falling or staying asleep
• Vomiting
• Problems with balance or coordination

Serious Side Effects

Some side effects can be severe. Seek medical attention immediately if you notice:

• Serious Skin Reactions: A skin rash, blisters, or peeling skin. These reactions can occur at any time during treatment and may be life-threatening.
• Breathing Issues: Slow, shallow, or difficult breathing.
• Mental Health Changes: New or worsening depression, suicidal thoughts, or unusual changes in mood or behavior, such as increased aggression or irritability.
• Allergic Reactions: Swelling of the face, lips, or tongue, or difficulty swallowing.
• Signs of Infection: Persistent fever, sore throat, or other signs of illness.

Boxed Warnings

Opioid Interaction: Using Onfi with opioid medications can cause severe drowsiness, breathing difficulties, coma, and death. This combination is generally avoided unless other treatment options are not sufficient.

Abuse and Addiction: As a benzodiazepine, Onfi carries risks of abuse, misuse, and addiction. These behaviors increase the risk of overdose and death.

Withdrawal: Physical dependence can develop with regular use. Stopping the medication suddenly or reducing the dose too quickly can cause serious withdrawal symptoms, such as seizures that do not stop, hallucinations, and shaking.

Serious Skin Reactions

Onfi is associated with rare but life-threatening skin conditions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These can happen at any time but are most likely in the first two months of treatment. Signs include a painful rash, blistering, or peeling skin.

DRESS Syndrome

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a serious hypersensitivity reaction reported with this medication. It may present as a rash combined with fever, swollen glands, or inflammation of internal organs.

Suicidal Thoughts and Behavior

Anti-seizure drugs, including Onfi, may increase the risk of suicidal thoughts or behaviors. Changes in mood, worsening depression, or any thoughts of self-harm should be monitored closely.

Sedation and Alertness

Onfi commonly causes sleepiness and decreased mental alertness. This can make it dangerous to drive or use heavy machinery. These effects may be worse if the medication is combined with alcohol or other drugs that cause drowsiness.

Pregnancy

Onfi may cause harm to an unborn baby. Research suggests that using benzodiazepines during pregnancy may increase the risk of birth defects. Additionally, infants exposed to the drug late in pregnancy may experience withdrawal symptoms or respiratory depression. Symptoms in newborns may include:

• Excessive sleepiness
• Feeding difficulties
• Decreased muscle tone
• Breathing problems

It is important to discuss the risks and benefits of treatment with a healthcare provider. Do not stop taking Onfi suddenly, as this can cause serious seizures that may harm the pregnancy. Patients are encouraged to join the North American Antiepileptic Drug Pregnancy Registry to help monitor the safety of the medication.

Breastfeeding

Clobazam passes into breast milk and can cause side effects in a nursing infant, such as sedation or trouble feeding. Healthcare providers typically recommend weighing the necessity of the drug against the benefits of breastfeeding. If breastfeeding while taking Onfi, monitor the infant closely for signs of excessive drowsiness or poor weight gain.

Available Forms

Onfi is provided in two different oral formulations:

• Tablets: These are solid tablets that can be taken whole or crushed and mixed with applesauce. They are scored, which means they can be split into equal halves if a partial dose is required.
• Oral Suspension: This is a liquid form of the medication. It is a suspension that must be shaken well before each use. It is intended to be measured and administered using the specific oral syringes provided with the medication to ensure the correct amount is taken.

FDA Approval and Indications

Onfi was approved by the U.S. Food and Drug Administration (FDA) in 2011. It is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.

Controlled Substance Status

As a benzodiazepine, Onfi is classified as a Schedule IV controlled substance. This designation indicates that the medication has a potential for abuse and may lead to physical or psychological dependence.

Boxed Warning

The FDA requires a boxed warning for Onfi due to several serious risks:

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

Safety Communications

The FDA has issued safety communications regarding serious skin reactions associated with Onfi. In 2013, the agency warned that the drug could cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be fatal. In 2023, the FDA issued an additional warning regarding the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a serious hypersensitivity reaction that can affect internal organs and requires immediate medical attention.

Risks of Abrupt Discontinuation

Onfi is a benzodiazepine, and stopping it suddenly can lead to physical and psychological withdrawal symptoms. The most severe risk is the development of seizures, including status epilepticus, which is a life-threatening condition where seizures do not stop. These risks are higher if the medication has been used at high doses or for a long duration.

Common Withdrawal Symptoms

Withdrawal symptoms may begin shortly after the dose is reduced or stopped. They can include:

• Anxiety, nervousness, or agitation
• Insomnia or trouble sleeping
• Tremors or muscle twitching
• Sweating and rapid heartbeat
• Stomach and muscle cramps
• Hallucinations or confusion

Safe Tapering Process

To minimize the risk of withdrawal, Onfi should always be discontinued gradually under the supervision of a healthcare professional. Your doctor will provide a tapering schedule to slowly lower the dose. If you experience any unusual symptoms or a return of seizures during this process, seek medical attention immediately.