Carbamazepine Overdose- Symptoms and Management

Introduction

Carbamazepine can be used alone or in combination with other drugs to treat seizures in epilepsy patients. It can also be used to treat nonepileptic conditions like bipolar disorder, neuropathic pain, schizophrenia, depression, and trigeminal neuralgia. Carbamazepine overdose is a common condition due to the drug's widespread use. It can happen due to accidental ingestion of large doses or may be due to long-term exposure to drug doses more than needed. Toxicity due to drug overdose may cause drowsiness, imbalance, abnormal cardiac conduction, dizziness, and coma. Toxic effects associated with Carbamazepine overdose are aggravated when the drug is taken in combination with other anti-epileptic drugs (Lamotrigine).

What Are Carbamazepines?

Carbamazepine is an anticonvulsant medication used to treat neuropathic pain and epilepsy. Swiss chemist Walter Schindler discovered it in the year 1953. Carbamazepine is considered a generic drug and is one of the drugs on the world health organization's list of essential medicines. Carbamazepine is available as tablets (100 milligrams, 200 milligrams), suspensions,extended-release tablets (100 milligrams, 200 milligrams, 300 milligrams, 400 milligrams), and solutions. They exert therapeutic effects by modulating the voltage-gated sodium channels (VGSC). These modulations cause reduced synaptic transmission and inhibition of action potential. Carbamazepine inactivates sodium channels and prevents the generation of an action potential.

What Are the Uses of Carbamazepine?

Carbamazepine can be used alone or in combination with other drugs to manage seizures in epileptic patients (generalized tonic seizures, partial seizures, mixed seizures), trigeminal neuralgia, bipolar disorder (mixed and acute manic type), schizophrenia, fibromyalgia, neuropathic pain, restless leg syndrome, alcohol withdrawal syndrome, and dementia (to reduce aggression and agitation).

What Are the Side Effects of Using Carbamazepine?

In some people, Carbamazepine use may result in dangerous allergic reactions called toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). These life-threatening allergic reactions cause severe damage to the internal organs and skin. Therefore, proper allergic drug history must be made before starting Carbamazepine medication.

Other side effects observed after Carbamazepine use are the following.

• Dry mouth.

• Dizziness.

• Nausea.

• Confusion.

• Vomiting.

• Fatigue.

• Vision changes.

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• Headache.

• Skin rashes.

• Facial swellings.

• Loss of appetite.

• Reduced blood cell count.

• Dark urine.

• Swollen eyes.

• Stomach pain.

• Gastric ulcers.

• Muscle pain.

• Mouth sores.

• Generalized weakness.

• Skin blisters.

• Yellow skin.

What Is Carbamazepine Toxicity?

Carbamazepine overdose results in central nervous system depression and adverse effects. These drugs have a high volume of distribution and protein binding capacity. Hence they can remain in the tissues in a bound form with plasma proteins. After reaching the tissues, they readily get absorbed and enter the bloodstream. Carbamazepine is oxidized to a metabolite known as Carbamazepine epoxide and exerts toxic effects. Other Carbamazepine derivatives like dihydroxy epoxide are also involved in toxicity-related adverse effects. Poisonous effects observed after ingestion depends on the amount of Carbamazepine.

The table given below shows the impact observed on different levels of Carbamazepine.

What Are the Symptoms of Carbamazepine Toxicity?

Clinical symptoms associated with toxicity develop within one to two hours for immediate-release tablets and four to eight hours for sustained-release tablets. Toxicity and severity of symptoms depend on drug concentration and patient response.

The common symptoms associated with Carbamazepine overdose are the following.

• Drowsiness.

• Restlessness.

• Unconsciousness.

• Dizziness.

• Muscle twitching.

• Vision changes.

• Nausea.

• Sedation.

• Abnormal movements.

• Rapid heartbeat.

• Vomiting.

• Unsteadiness.

• Irregular breathing.

• Difficulty in urination.

• Slow breathing.

• Cardiac arrhythmias (life-threatening).

• Seizures.

• Ataxia.

• Coma.

How Can We Manage Carbamazepine Toxicity?

• Gastrointestinal Decontamination - Gastric lavage can be done in cases of Carbamazepine toxicity to eliminate the ingested toxins when the patient is admitted into the hospital within a few hours. Activated charcoal can be used to prevent absorption and reduce toxicity. It binds to Carbamazepine molecules and prevents gastrointestinal absorption of the drug. In addition to that, activated charcoal interrupts the enterohepatic circulation of Carbamazepine and enhances drug elimination. Gastric decontamination using activated charcoal poses the risk of charcoal aspiration in patients with an altered unconscious and mental status due to overdose. Charcoal hemoperfusion can also be done in patients to enhance Carbamazepine elimination and improve clinical outcomes.

• Enhanced Elimination - Repeated use of activated charcoal is done to enhance the elimination of ingested toxins. It can be achieved using multiple-dose activated charcoal (MDAC).

• Intravenous Fluids - Fluid resuscitation must be done in patients with Carbamazepine toxicity to manage hypotension and hypovolemia.

• Hemodialysis - In cases of fatal Carbamazepine poisoning, toxic metabolites like Carbamazepine epoxide can be eliminated from the blood using hemodialysis. This technique purifies toxin-loaded blood from the body using a hemodialysis machine. Thus toxic effects associated with drug overdose can be managed to desired levels.

• Intravenous Lipid Emulsion (ILE) - Lipid emulsions can also be used in cases of severe Carbamazepine toxicity to reduce neurotoxicity and cardiotoxicity.

• Venovenous Hemodiafiltration (CVVHDF) - It is done mainly in pediatric patients following Carbamazepine toxicity. Children are at high risk for developing severe adverse effects after a Carbamazepine overdose. Continuous venovenous hemodiafiltration can be done to enhance the clearance of toxins. In this technique, diffusion and convection techniques are used to increase the volume of ultrafiltrate and thereby enhance the clearance rate. It can also be performed in unstable adult patients to reduce toxicity.

• Sodium Bicarbonate - Ventricular dysrhythmia due to Carbamazepine toxicity can be managed with sodium bicarbonate.

• Benzodiazepines - Intravenous administration of benzodiazepine drugs can manage seizures associated with Carbamazepine toxicity. Drugs such as Lorazepam, Midazolam, and Diazepam are commonly used.

Conclusion:

Carbamazepine drugs are commonly used to manage seizures in epilepsy patients. They are one of the most commonly used drugs in the world. Hence drug overdose and toxicity associated with Carbamazepine medications are also common. Neurotoxicity associated with Carbamazepine overdose may cause altered consciousness, confusion, loss of muscle balance, depression, and respiratory arrest. Immediate hospital admission must be made after a Carbamazepine overdose to avoid life-threatening complications. Enhanced drug elimination techniques will help to remove the ingested toxins and reduce symptoms to a certain extent. Other clinical symptoms associated with Carbamazepine overdose can be managed with necessary medical treatment.