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Grapefruit and Tegretol

author image Stephen Christensen
Stephen Christensen started writing health-related articles in 1976 and his work has appeared in diverse publications including professional journals, “Birds and Blooms” magazine, poetry anthologies and children's books. He received his medical degree from the University of Utah School of Medicine and completed a three-year residency in family medicine at McKay-Dee Hospital Center in Ogden, Utah.
Grapefruit and Tegretol
A sliced grapefruit on a plate. Photo Credit: amanaimagesRF/amana images/Getty Images

Tegretol, or carbamazepine, is an anticonvulsant medication used to treat certain kinds of epileptic seizures. In the three decades since Tegretol hit the U.S. market, physicians have found it useful for treating several other conditions, such as bipolar disorder, restless legs syndrome, drug withdrawal symptoms and chronic pain syndromes. Tegretol works by decreasing the “excitability” of nerve cells and inhibiting the conduction of impulses through neural networks. This activity also accounts for many of Tegretol’s side effects, which can increase when other medications or foods compete with Tegretol for metabolism.

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Tegretol Side Effects

Carbamazepine carries a fairly impressive profile of adverse effects, but some are far more common than others. Drowsiness, headaches and impaired coordination are common, as is a decreased tolerance for alcohol. These side effects often abate with continued use of the drug. Blurred vision and hearing abnormalities occasionally occur, as do heart rhythm disturbances, blood cell abnormalities and electrolyte changes. According to “Orphanet Journal of Rare Diseases,” a rare and potentially fatal complication of Tegretol usage is a condition called Stevens-Johnson syndrome, which causes a breakdown in the skin and mucous membranes.

Tegretol Metabolism

Like many drugs, carbamazepine is metabolized by enzymes in your gut and liver. These enzymes are responsible for detoxifying foreign substances and eliminating them from your body. In a process called autoinduction, Tegretol actually increases the activity of the very enzymes, called CYP3A4, that break it down. When you first start taking Tegretol, your dosage usually has to be adjusted upward for several days as autoinduction occurs. Eventually, enzymatic activity reaches a maximum plateau, at which point your dosage is also leveled off.

Competition for Enzymes

The CYP3A4 enzyme complex is responsible for detoxifying a plethora of substances, and, like any other physiologic process in your body, its compensatory abilities are limited. If the CYP3A4 complex is overwhelmed by too many different substances at once or by an agent that inhibits its activity, it cannot perform its job in a timely manner. When this occurs, potentially toxic materials “back up” in your bloodstream and tissues until the enzymes are once again available. Higher blood concentrations of many drugs, including Tegretol, lead to increased side effects.

Interaction With Grapefruit

For at least the last decade, scientists have known that grapefruit and grapefruit juice inhibit the CYP3A4 enzyme complex. As early as 1998, researchers demonstrated that the consumption of grapefruit increased blood levels of Tegretol. A 2000 review in “Mayo Clinic Proceedings” discussed the interactions between grapefruit and a number of prescription drugs and explored the possible molecular basis for these interactions. In the ensuing decade, more medications have been added to the list of drugs that interact -- sometimes fatally -- with grapefruit.


If you take Tegretol, its optimal effects may depend on maintaining your blood levels between critical minimum and maximum values. Grapefruit, by inhibiting the enzymes that metabolize Tegretol, can increase your drug levels to a dangerous degree. You should avoid grapefruit when you are taking this medication. Talk with your doctor about other foods and medications that can interfere with Tegretol.

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