What are the potential interactions with Tegretol (carbamazepine)?

Potential Drug Interactions with Tegretol (Carbamazepine)

Carbamazepine has numerous significant drug interactions that can affect both its own levels and the levels of other medications, requiring careful monitoring and dose adjustments to prevent toxicity or therapeutic failure. 1

Major Interaction Categories

Drugs That Increase Carbamazepine Levels

• CYP3A4 inhibitors can significantly increase plasma carbamazepine levels, potentially leading to toxicity:
  • Macrolide antibiotics (erythromycin, clarithromycin)
  • Antifungals (ketoconazole, itraconazole, fluconazole, voriconazole)
  • Antidepressants (fluoxetine, fluvoxamine)
  • Other medications: cimetidine, diltiazem, verapamil, omeprazole, isoniazid, danazol, protease inhibitors 1
  • Grapefruit juice

Drugs That Decrease Carbamazepine Levels

• CYP3A4 inducers can decrease carbamazepine levels, potentially reducing efficacy:
  • Other antiepileptics (phenytoin, phenobarbital, primidone)
  • Rifampin, rifabutin
  • Cisplatin, doxorubicin
  • Theophylline, aminophylline 1

Drugs Affected by Carbamazepine

• Carbamazepine is a potent inducer of CYP3A4, CYP1A2, CYP2B6, and CYP2C8/9/19, causing decreased levels of many medications:
  • Oral contraceptives (reduced effectiveness)
  • Warfarin (reduced anticoagulant effect)
  • Immunosuppressants (cyclosporine, tacrolimus)
  • Antipsychotics and antidepressants
  • Corticosteroids
  • Many other medications metabolized by these enzymes 1

Critical Interactions Requiring Special Attention

Anticonvulsants

• Valproic acid: Increases carbamazepine-10,11-epoxide (active metabolite) concentrations, potentially causing toxicity. Requires therapeutic drug monitoring and possible dose adjustment 2
• Phenytoin: Bidirectional interaction - phenytoin decreases carbamazepine levels while carbamazepine decreases phenytoin levels 3

Cardiovascular Medications

• Digoxin: Carbamazepine decreases digoxin levels; therapeutic drug monitoring and dose increases may be required 2
• Calcium channel blockers: Diltiazem and verapamil increase carbamazepine levels while carbamazepine decreases their effectiveness 1
• Warfarin: Carbamazepine decreases warfarin efficacy; monitoring of INR and dose adjustments needed 2

Anti-infectives

• Rifampin: Decreases carbamazepine levels significantly 2
• Macrolide antibiotics: Increase carbamazepine levels, potentially causing toxicity 1
• Isoniazid: Increases carbamazepine levels and risk of hepatotoxicity 2

Psychotropic Medications

• SSRIs: Fluoxetine and fluvoxamine increase carbamazepine levels 1
• Antipsychotics: Carbamazepine decreases levels of many antipsychotics, requiring dose adjustments 1
• Tricyclic antidepressants: Carbamazepine decreases their levels, potentially reducing efficacy 3

Direct-Acting Antivirals (DAAs) for Hepatitis C

• Sofosbuvir-based regimens: Carbamazepine is contraindicated due to significant reduction in DAA levels and potential treatment failure 2

Other Critical Interactions

• Oral contraceptives: Carbamazepine significantly reduces their effectiveness; alternative contraception methods recommended 1
• Immunosuppressants: Monitoring of tacrolimus and cyclosporine levels required with dose adjustments 1

Monitoring Recommendations

1. Baseline and periodic monitoring:

   • Complete blood count
   • Liver function tests
   • Carbamazepine serum levels (therapeutic range: 4-12 μg/mL)
   • Kidney function tests 1

2. Therapeutic drug monitoring is essential when:

   • Starting or stopping interacting medications
   • Observing unexpected toxicity or reduced efficacy
   • Adjusting doses 1

Common Pitfalls to Avoid

1. Failure to recognize enzyme induction: Carbamazepine's enzyme-inducing effects may take 2-3 weeks to develop fully and persist for 2-4 weeks after discontinuation.

2. Overlooking contraceptive failure: Women of childbearing potential should be advised about reduced contraceptive efficacy and need for alternative methods.

3. Missing biphasic interactions: Some drugs (like phenytoin) may initially increase carbamazepine levels through protein displacement but later decrease levels through enzyme induction 2.

4. Ignoring formulation differences: Suspension forms may produce higher peak levels than tablets at the same dose, potentially affecting side effect profiles 1.

5. Overlooking herbal interactions: St. John's wort significantly decreases carbamazepine levels 2.

When prescribing carbamazepine, always check for potential drug interactions, monitor appropriate parameters, and adjust doses as needed to maintain therapeutic efficacy while minimizing toxicity.