What are the potential drug interactions with carbamazepine (Tegretol) 200mg?

From the Guidelines

Carbamazepine (Tegretol) 200 mg should be used with caution due to its potential to interact with various medications, including warfarin, which may require a 50% increase in warfarin maintenance dose after initiation of carbamazepine, as seen in a large retrospective cohort study 1.

Key Interactions

• Carbamazepine is a strong CYP3A4 enzyme inducer, which can decrease the effectiveness of many medications, including oral contraceptives, warfarin, certain statins, and immunosuppressants like cyclosporine.
• Combining carbamazepine with MAO inhibitors, certain antidepressants (particularly some SSRIs like fluoxetine), macrolide antibiotics (erythromycin, clarithromycin), antifungals (ketoconazole, itraconazole), calcium channel blockers (verapamil, diltiazem), and certain HIV medications (protease inhibitors) should be avoided.
• Carbamazepine levels can be increased by grapefruit juice and decreased by St. John's wort.

Monitoring and Precautions

• Always inform all healthcare providers about carbamazepine use before starting any new medication.
• Consider the need for dosage adjustments of either carbamazepine or the interacting drug.
• Monitor patients for potential side effects and interactions, particularly when combining carbamazepine with other medications that may be affected by its enzyme-inducing properties.

Specific Considerations

• Apremilast, a medication used to treat psoriasis, should not be used with carbamazepine due to the potential for decreased efficacy 1.
• Other medications that are strong inducers of cytochrome P450, such as rifampin and phenytoin, may also interact with carbamazepine and should be used with caution.

From the FDA Drug Label

Clinically meaningful drug interactions have occurred with concomitant medications and include (but are not limited to) the following: Agents That May Affect Carbamazepine Plasma Levels When carbamazepine is given with drugs that can increase or decrease carbamazepine levels, close monitoring of carbamazepine levels is indicated and dosage adjustment may be required Agents That Increase Carbamazepine Levels CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels. Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides (e.g., erythromycin, clarithromycin), fluoxetine, fluvoxamine, trazodone, omeprazole, oxybutynin, isoniazid, niacinamide (nicotinamide), azoles (e.g., ketaconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, and protease inhibitors. Agents That Decrease Carbamazepine Levels CYP3A4 inducers can increase the rate of carbamazepine metabolism. Drugs that have been shown, or that would be expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl, felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline

The carbamazepine (Tegretol) 200 mg drug has several drug-to-drug interactions.

• Agents that increase carbamazepine levels include CYP3A4 inhibitors such as aprepitant, cimetidine, and ciprofloxacin.
• Agents that decrease carbamazepine levels include CYP3A4 inducers such as cisplatin, doxorubicin HCl, and felbamate. When carbamazepine is given with these drugs, close monitoring of carbamazepine levels is indicated and dosage adjustment may be required 2. Some specific interactions include:
• When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled.
• When carbamazepine is used with tacrolimus, monitoring of tacrolimus blood concentrations and appropriate dosage adjustments are recommended.
• The use of concomitant strong CYP3A4 inducers such as carbamazepine should be avoided with temsirolimus.
• The use of carbamazepine with lapatinib should generally be avoided.
• Coadministration of carbamazepine with nefazodone is contraindicated 2.

From the Research

Carbamazepine (Tegretol) 200 mg Drug to Drug Interaction

• Carbamazepine is known to interact with various drugs, affecting its pharmacokinetics and potentially leading to clinically significant interactions 3.
• The most important interactions affecting carbamazepine pharmacokinetics are those resulting in induction or inhibition of its metabolism, with drugs such as phenytoin, phenobarbital, and primidone accelerating its elimination 3.
• Inhibition of carbamazepine metabolism can be caused by stiripentol, remacemide, acetazolamide, macrolide antibiotics, isoniazid, metronidazole, certain antidepressants, verapamil, diltiazem, cimetidine, danazol, and propoxyphene, potentially leading to toxic concentrations 3.
• Carbamazepine is a potent inducer of CYP3A4 and other oxidative enzyme systems in the liver, which can accelerate the metabolism of concurrently prescribed anticonvulsants and other drugs, such as valproic acid, clonazepam, ethosuximide, lamotrigine, topiramate, tiagabine, and remacemide 3.

Interaction with Warfarin

• The initiation and discontinuation of carbamazepine can affect antithrombotic control in patients receiving warfarin, with a case report documenting a drop in INR from 3.3 to 1.3 after starting carbamazepine 200 mg/day 4.
• Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme, necessitating an increase in warfarin dosage to maintain the INR in the therapeutic target range 4.
• A register-based nationwide cohort study involving the Swedish population found that the average warfarin doses were 49% higher during carbamazepine treatment, with subtherapeutic INR levels observed in 79% of patients during the fifth week of cotreatment 5.

Other Interactions

• Carbamazepine may accelerate the metabolism of phenytoin, phenobarbital, primidone, valproic acid, and warfarin, while phenytoin, phenobarbital, and primidone may increase the hepatic metabolism of carbamazepine 6.
• Inhibition of the metabolism of carbamazepine has been caused by triacetyloleandomycin, erythromycin, propoxyphene, isoniazid, and cimetidine 6.
• The bioavailability and steady-state fluctuations of Tegretol commercial and carbamazepine OROS tablets have been compared in adult and pediatric epileptic patients, demonstrating the bioequivalence of carbamazepine OROS with Tegretol commercial tablets over a 24-h treatment interval 7.