Lamictal XR (lamotrigine), developed by GlaxoSmithKline, is an approved treatment for epilepsy and bipolar I disease. The drug was first approved by the US Food and Drug Administration (FDA) in 1994. Over the years the drug has been tested and approved as monotherapy as well as in combination with other drugs.
In January 2010, Lamictal was granted approval as an add-on therapy for epilepsy. The approval allowed for the use of extended release tablets of Lamictal as a daily prescription in patients who are aged 13 years and older and suffer from primary generalised tonic-clonic seizures. These seizures are the most common form of generalised seizures in epilepsy.
In August 2010, the FDA issued a warning to consumers that Lamictal can cause aseptic meningitis. The connection between Lamictal and aseptic meningitis was established during the FDA’s regular adverse event monitoring and communications with GlaxoSmithKline.
The regulator has recommended discontinuation of the drug if the exact cause for meningitis is not identified. It has also suggested that in suspected cases of meningitis, the cause of the disease should be diagnosed promptly to start the treatment.
Epilepsy is a neurological disorder in which a person suffers from periodic electrical disturbances in the brain, known as seizures.
The type of seizure depends upon the part of brain which is affected and to what extent it is affected. If the seizure involves the entire brain, then it is termed as a generalised seizure, and if only part of the brain is involved, it is called a partial seizure. Children and people above the age of 65 are normally affected by the condition.
Seizures due to epilepsy may be caused due to brain injury or hereditary reasons. However, in almost 70% of cases, the exact cause of epilepsy is unknown. People suffering from epilepsy may suffer from more than one type of seizure, as it is only a symptom.
For effective treatment, the type of epilepsy needs to be identified before beginning treatment. The majority of the seizures resulting from epilepsy can be controlled by drugs and diet.
Lamictal – sodium channel inhibitor
Lamictal works by inhibiting the voltage-dependent sodium channels. It stabilises the neurons, which produce glutamate and aspartate, resulting in their decreased release. The drug is available in the form of an immediate-release formulation and as extended release tablets. The drug was first approved in 1994 for the treatment of partial seizures.
In 1998, Lamictal became one of the very few treatments approved for the treatment of Lennox-Gastaut syndrome, a severe childhood-onset type of epilepsy. In 2003, the drug was approved for the treatment of bipolar I disease, a psychiatric condition characterised by elevated moods or mania.
In the same year, the drug was approved for the treatment of paediatric epilepsy patients aged two years. In May 2009, Lamictal was approved for the treatment of partial onset seizures with or without secondary generalisation in patients 13 years and older.
Lamictal clinical trials
Phase I trials for Lamictal involved testing the drug as monotherapy in newly-diagnosed typical absence seizures in children less than the age of 13 years. Phase II trials for Lamictal included two studies in paediatric patients aged between 1 and 24 months. One Phase II study tested the safety and efficacy of Lamictal with the current treatment for partial seizures. The second Phase II study was a long-term safety trial in patients enrolled in the first Phase II study.
Phase III clinical studies for Lamictal involved several trials, which tested the safety and efficacy of the drug in treating partial seizures, primary generalised tonic-clonic seizures and bipolar I disease.
The approval of Lamictal in the form of extended release tablets in January 2010 was based on two pivotal Phase III trials, ARMOR and COMPASS. The ARMOR trial enrolled 326 patients and involved patients older than 13 years suffering from uncontrolled partial seizures.
The COMPASS study compared the safety and efficacy of immediate-release Lamictal to once-daily Lamictal in patients 13 years or older suffering with epilepsy.
Lamictal drug sales
Lamictal is one of GSK’s top-selling drugs. However, with the expiry of the drug’s patent, there has been an increase in generic competition. The recent approval of extended release tablets of Lamictal is expected to boost its sales, which are being lost due to competition from generics.