Lamotrigine, also known as Lamictal, is an anti-seizure medication that was approved by the FDA for treatment of epilepsy and bipolar disorder. Lamotrigine is used alone or with other medicines to treat seizures in patients two years and older. It may also be used as maintenance treatment in patients with bipolar disorder to help delay the occurrence of mood episodes such as depression, mania, or hypomania. Stopping lamotrigine without first talking to a prescriber can lead to uncontrolled seizures, or new or worsening mental health problems. Lamotrigine has been approved and on the market for 24 years, and is available under the brand name Lamictal and as generics.
Lamictal was first sold in the United States in 1994 and is manufactured by GlaxoSmithKline. It is a sodium channel blocker that helps by suppressing the excitatory neurotransmitters in the central nervous system. Lamictal is available both as an oral tablet and in a chewable form and is metabolized by the liver. Between 2005 and 2015, there were more than 900,000,000 prescriptions for Lamictal in the United States. Lamictal has been one of GlaxoSmithKline’s best-selling drugs of all time and sales between March 2007 and March 2008 exceeded $2 billion.
A paper written in 2008 by Nasser et al. reviewed evidence from Lamictal trials that were unpublished, and it concludes that lamotrigine has "very limited, if any, efficacy in the treatment of acute bipolar depression". A 2008 paper by Calabrese et al. examined much of the same data, and found that in five placebo-controlled studies, lamotrigine did not significantly differ from placebo in the treatment of bipolar depression.
Lamictal and HLH
A very serious immune system reaction has been identified as a side-effect resulting from the use of Lamictal. This immune system reaction is called HLH (which stands for hemophagocytic lymphohistiocytosis) which causes the immune system to damage the body’s tissues and organs. This can cause severe inflammation throughout the body and lead to hospitalization and death, especially if the reaction is not diagnosed and treated quickly. HLH typically presents as a persistent fever, usually greater than 101°F, and it can lead to severe problems with blood cells and organs throughout the body such as the liver, kidneys, brain and lungs.
Information on HLH
According to the FDA, a diagnosis of HLH can be established if a patient has at least five of the following eight signs or symptoms:
- fever and rash
- enlarged spleen
- elevated levels of triglycerides or low blood levels of fibrinogen
- high levels of blood ferritin
- hemophagocytosis identified through bone marrow, spleen, or lymph node biopsy
- decreased or absent Natural Killer (NK) Cell activity
- elevated blood levels of CD25 showing prolonged immune cell activation
Patients or their caregivers should contact their health care professionals right away if they experience any symptom of HLH while taking lamotrigine. HLH can occur within days to weeks after starting treatment. A physical examination and specific laboratory blood tests and other evaluations are used to diagnose HLH. Signs and symptoms of HLH include but are not limited to:
- enlarged liver; symptoms may include pain, tenderness, or unusual swelling over the liver area in the upper right belly
- swollen lymph nodes
- skin rashes
- yellow skin or eyes
- unusual bleeding
- nervous system problems, including seizures, trouble walking, difficulty seeing, or other visual disturbances
FDA Action for Safety
On April 25, 2018, the FDA issued a warning that Lamictal can cause this rare, but very serious reaction. Because of the association with HLH, the FDA required the manufacturer of Lamictal to add a new warning about the risk of HLH to the prescribing information in the lamotrigine drug labels. The FDA also issued an alert to healthcare professionals stating they should be aware that prompt recognition and early treatment is important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms such as fever and rash are not specific. HLH may also be confused with other serious immune-related adverse reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
In the 24 years since lamotrigine’s 1994 approval, the FDA identified many cases worldwide of confirmed or suspected HLH associated with the medicine in children and adults. This number includes only reports submitted to FDA and found in the medical literature, so there are likely additional cases about which the FDA is unaware. The FDA determined that “there was reasonable evidence that lamotrigine was the cause of HLH” in these cases based on the timing of events and the order in which they occurred. The patients in these cases required hospitalization and received drug and other medical treatments, with one patient dying.
Talk to a Lawyer
Lamictal has injured thousands of people who had no idea that the drug was dangerous. If you or a loved one has been diagnosed with HLH while on Lamictal, contact Napoli Shkolnik PLLC and talk with an experienced pharmaceutical litigation attorney in New York. We do not charge upfront legal fees in negligence cases.