Zonisamide (Zonegran) Risks, Warnings, and Complications

ALLERGIC REACTIONS TO SULFONAMIDES: Zonisamide belongs to a group called sulfa drugs or sulfonamides. There are rare reports of severe allergic reactions to these drugs, including toxic epidermal necrolysis, Stevens-Johnson syndrome, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Before starting zonisamide therapy, tell your doctor if you have a sulfa allergy. 

SERIOUS SKIN REACTIONS: In a small number of people, zonisamide can cause severe, life-threatening skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Stop taking zonisamide immediately and seek emergency medical care if you develop a skin rash on this medicine. The rash typically occurs in the first 16 weeks of treatment. Serious skin reactions on zonisamide are unrelated to the dose and can occur at low doses as well. 

SERIOUS HEMATOLOGIC EVENTS: There are case reports of serious hematologic complications such as aplastic anemia and agranulocytosis in people taking zonisamide. It is unclear if the dose or treatment duration affects the risk of these problems. 

DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) OR MULTI-ORGAN HYPERSENSITIVITY: Zonisamide use has been linked to a serious complication called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or multi-organ hypersensitivity, which can be life-threatening or fatal. 

Seek emergency medical attention if you develop signs and symptoms of DRESS, such as fever, skin rash, enlarged lymph nodes, or facial swelling. DRESS can affect many organs in the body, including the liver, kidneys, heart, muscles, and blood. The symptoms sometimes resemble an acute viral illness. 

OLIGOHYDROSIS AND HYPERTHERMIA IN CHILDREN: Zonisamide treatment can result in oligohidrosis (decreased sweating) and hyperthermia (elevated body temperature), especially in pediatric patients. This can result in heat stroke, requiring hospitalization. Zonisamide is not approved for use in children under 16 years of age. 

If you are on zonisamide, monitor carefully for decreased sweating and increased body temperature, especially in hot weather. 

Give your doctor a complete list of your medications. Certain other drugs can increase the risk of heat-related problems, such as anticholinergic medications and carbonic anhydrase inhibitors. 

ACUTE MYOPIA AND SECONDARY ANGLE CLOSURE GLAUCOMA: Serious eye problems such as acute myopia and secondary angle closure glaucoma have been reported in people who received zonisamide. Glaucoma is an eye condition in which the intraocular pressure is elevated. Left untreated, it can lead to permanent loss of vision. 

Tell your doctor immediately or seek emergency medical care if the medication affects your eyes and you develop decreased vision, double vision, or eye pain while on zonisamide. These symptoms typically occur within one month of starting treatment with zonisamide. 

SUICIDAL BEHAVIOR AND IDEATION: Anti-epileptic medications, including zonisamide, are associated with an increased risk of suicidal thoughts or behaviors. Before starting zonisamide, tell your doctor if you have a history of mental illness such as depression or suicidal ideation. 

You and your family members should seek immediate medical attention if there are any unusual changes in behavior or mood, such as new or worsening depression or thoughts of self-harm. Suicidal thoughts or behavior can occur as early as one week after starting zonisamide therapy and the risk continues to be present as long as you are on the drug. 

METABOLIC ACIDOSIS: Taking zonisamide can lead to a chemical disturbance in the body called metabolic acidosis, in which serum bicarbonate levels are decreased. This complication generally occurs early during treatment but can occur at any time and at any dose. Risk factors for metabolic acidosis on zonisamide include status epilepticus, kidney disease, lung disorders, diarrhea, ketogenic diet, and certain drugs. 

Seek emergency medical care for signs and symptoms of metabolic acidosis, such as fast and shallow breathing, irregular heartbeat, fatigue, or loss of appetite. 

Chronic, untreated metabolic acidosis can increase the risk of kidney stones (nephrolithiasis or nephrocalcinosis), hyperammonemia (high ammonia levels), and bone problems like osteomalacia (rickets in children) and/or osteoporosis (weak bones) and an increased risk for bone fractures. Pediatric patients on zonisamide may have slowed growth rates and a reduction in maximum height achieved. 

WITHDRAWAL SEIZURES: In people with epilepsy, suddenly stopping zonisamide can result in increased seizure frequency or status epilepticus. Do not abruptly stop zonisamide. Your healthcare provider will tell you how to reduce the dose slowly. 

TERATOGENICITY: Zonisamide can cause severe harm to the unborn baby if it is taken during pregnancy, including birth defects and fetal death. Because of the risk of teratogenicity, women of childbearing age should use appropriate birth control while on zonisamide. 

COGNITIVE AND NEUROPSYCHIATRIC EFFECTS: Zonisamide frequently causes central nervous system (CNS) adverse effects, including psychiatric side effects such as depression and psychosis, cognitive side effects such as problems with concentration, language, or speech, and CNS side effects like sleepiness and fatigue. 

These side effects are more likely in the first 4-10 weeks of treatment and at higher doses of zonisamide above 300 mg per day. Be careful while driving and doing other potentially hazardous activities until you know how zonisamide affects you. 

HYPERAMMONEMIA AND ENCEPHALOPATHY: Hyperammonemia (high ammonia levels) and encephalopathy (brain changes) have been reported in people who took zonisamide. These effects may be due to zonisamide-induced metabolic acidosis.

Before starting treatment, tell your doctor if you are taking other anti-seizure medications such as valproic acid and topiramate which can have an additive effect and increase the risk of hyperammonemia. Seek emergency medical care for any changes in mental status, lethargy, or vomiting.