The FDA announced that Onfi (clobazam), an anti-seizure drug, can cause rare but severe skin reactions resulting in permanent harm and death. Two such skin reactions are Stevens-Johnson Syndrome (SJS) and Toxic Epidural Necrolysis (TEN). These immune-mediated diseases cause loss of the epidermal skin layer that can result in death.
The FDA has identified 20 cases of SJS/TEN associated with the medication, and this product has seriously injured at least five children.
Stevens-Johnson syndrome can first appear to be a rash but increases in intensity to large blistery hives. If not diagnosed early enough, it can cause blindness and death. It is often hard to diagnose.
With Toxic Epidural Necrolysis, the epidermis, the top layer of skin, detaches from the dermis, the lower layers of the skin, all over the body. While it can affect many body parts, it most severely affects the mucous membranes, such as the mouth, eyes, and vagina. The severe findings of TEN are often preceded by 1 to 2 weeks of a fever.
FDA Label Changes
The FDA has approved changes to the medication’s label and guide that describe the risk, given the seriousness of these illnesses. The FDA advises health officials to discontinue Onfi at the first sign of rash, and a dermatologist should be consulted before these illnesses are ruled out. Patients should not stop taking Onfi without first talking to their health care professionals, as stopping Onfi suddenly can cause severe withdrawal problems, such as seizures that will not stop, hallucinations (hearing or seeing things that are not real), shaking, nervousness, and stomach or muscle cramps.
Onfi Side Effects
Onfi (clobazam) is a benzodiazepine medication primarily used to manage seizures associated with Lennox-Gastaut syndrome, a severe form of epilepsy. Since its approval by the FDA in 2011, Onfi has become a critical component in the treatment regimen of many patients suffering from this debilitating neurological condition.
No one is arguing Onfi should be taken off the market. But despite its benefits in controlling seizures, Onfi has been associated with various side effects and complications. The issues linked to Onfi usage can be broadly divided into immediate side effects, allergic reactions, and long-term complications.
Immediate Side Effects of Onfi
Immediate side effects of Onfi are similar to those of other benzodiazepines and may include drowsiness, sedation, drooling, constipation, cough, urinary incontinence, and respiratory problems. These side effects can severely impact the quality of life of the patients. They could also lead to dangerous situations, especially if the patient is drowsy or sedated while performing tasks that require alertness, like driving or operating heavy machinery.
Allergic Reactions to Onfi
Allergic reactions to Onfi can also occur, with symptoms such as hives, difficulty breathing, and swelling of the face, lips, tongue, or throat. A severe skin reaction, Stevens-Johnson syndrome (SJS), and its more serious form, toxic epidermal necrolysis (TEN), have also been reported. SJS/TEN, as we discussed above, is a life-threatening condition characterized by widespread skin rash, blisters, and sloughing off of the skin. The FDA warned in 2013 about the risk of SJS/TEN in patients taking Onfi, especially during the first eight weeks of treatment or when reintroducing the medication.
Long-Term Side Effects of Onfi
Long-term complications associated with Onfi primarily relate to its potential for physical and psychological dependence. As with other benzodiazepines, prolonged use of Onfi can lead to tolerance, meaning higher doses are required over time to achieve the same effect. This can create a vicious cycle, eventually leading to dependence and withdrawal symptoms when the medication is discontinued.
Withdrawal symptoms can be severe, including seizures, hallucinations, shaking, cramps, vomiting, sweating, and in rare cases, a condition known as benzodiazepine withdrawal syndrome. This syndrome can cause various symptoms, including anxiety, irritability, insomnia, and sensory disturbances, lasting for weeks or even months. Therefore, discontinuing Onfi should always be done under the supervision of a healthcare provider.
Moreover, a significant concern related to Onfi and other similar medications is their potential for misuse and addiction. While Onfi is a vital medication for patients with Lennox-Gastaut syndrome, the risk of misuse can be severe, particularly for those with a history of substance abuse. Benzodiazepines like Onfi are classified as Schedule IV controlled substances due to their potential for abuse and addiction.
Lennox-Gastaut Syndrome (LGS)
Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that typically appears in infancy or early childhood. This rare condition is characterized by multiple types of seizures and intellectual disability.
There are three main types of seizures in Lennox-Gastaut syndrome:
- Tonic seizures: A generalized tonic-clonic seizure, previously referred to as a grand mal seizure, is characterized by an initial stage of muscle stiffening (the tonic phase), followed by rhythmic muscle jerking (the clonic phase). This is the most common type of seizure with Lennox-Gastaut syndrome. They often occur during sleep. These seizures are typically linked to compromised awareness or a total blackout of consciousness.
- Atypical absence seizures: These involve a loss of consciousness and unresponsiveness, which may appear as staring. Unusual absence seizures have been documented in as many as 60% of individuals diagnosed with Lennox-Gastaut syndrome.
- Atonic or drop attacks: A atonic or drop attack can be described as any incident that results in a person abruptly falling to the ground. In the realm of epilepsy, these could be due to atonic seizures (a widespread loss of muscle tone) or tonic seizures (prolonged, generalized body rigidity). Drop attacks are indicative of Lennox-Gastaut syndrome but also occur in other epilepsy syndromes and causes. These types of seizures have a significant impact on quality of life, as they can lead to injuries, either from sudden, unpredictable falls (atonic seizures) or from being propelled forward or backward during tonic seizures.
The intellectual and behavioral problems associated with LGS can include developmental delays, learning disabilities, and behavioral problems such as hyperactivity, aggressiveness, and autistic-like behaviors.
The exact cause of LGS is unknown. In some cases, it’s associated with brain malformations, perinatal asphyxia (lack of oxygen), central nervous system infections, or genetic conditions. However, in many cases, the cause remains unknown.
Managing LGS is challenging and typically involves medications to control seizures, along with other therapies such as special education, behavior therapy, and sometimes dietary therapies like the ketogenic diet. In some cases, surgery or neurostimulation may be considered.
Despite the various treatment options, controlling seizures in LGS remains difficult, and the condition can greatly affect the quality of life.
All Drugs Come with Risks
The bottom line is that Onfi provides critical seizure control for patients with Lennox-Gastaut syndrome, which comes with real risk. Significant concerns are its potential side effects, the risk of severe allergic reactions, long-term complications including dependence and withdrawal, and the potential for misuse and addiction. Are the risks worth the benefits? It depends on the patient, and that decision is made with your doctor. This requires doctors to carefully consider these risks when prescribing Onfi and determine the best path. And it is also incumbent on the doctor to closely monitor for any adverse effects during treatment. Can the failure to do this be malpractice? Absolutely.
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