What medications interact with Daktarin (miconazole)?

Miconazole (Daktarin) Drug Interactions: Clinical Significance and Evidence

Miconazole (Daktarin) can interact with numerous medications through inhibition of CYP450 enzymes, particularly CYP2C9, with warfarin being the most clinically significant interaction that can lead to dangerous bleeding complications even when miconazole is used topically.

Key Drug Interactions with Miconazole

Warfarin and Other Anticoagulants

• Miconazole significantly enhances warfarin's anticoagulant effects by inhibiting the CYP2C9 isoenzyme 1, 2
• This interaction occurs not only with oral and vaginal formulations but also with topical applications that can be absorbed through the skin 2
• Multiple case reports document INR derangement and bleeding complications when warfarin is used concomitantly with miconazole oral gel 3
• Monitoring recommendations: Check baseline INR before starting miconazole, recheck within 3-5 days of starting treatment, and continue monitoring throughout treatment course 1

Other Significant Drug Interactions

CYP450 Substrate Medications

Miconazole can substantially increase the plasma concentrations of:

• Antihistamines: terfenadine, astemizole (risk of QT prolongation) 4
• Immunosuppressants: cyclosporin, tacrolimus 4
• Cardiovascular drugs: digoxin, felodipine 4
• Statins: lovastatin 4
• Benzodiazepines: midazolam, triazolam 4
• Oral hypoglycemics: glibenclamide (glyburide) 4
• Anticonvulsants: phenytoin 4
• HIV medications: ritonavir, saquinavir 4
• Antidepressants: nortriptyline 4

Drugs That Affect Miconazole

• Drugs that increase gastric pH (H2 receptor antagonists, proton pump inhibitors) may reduce the bioavailability of azole antifungals including miconazole 4
• Enzyme inducers like carbamazepine, phenobarbital, phenytoin, and rifampicin can reduce miconazole effectiveness 4

Route of Administration and Interaction Risk

The risk of drug interactions varies by administration route:

1. Oral gel/systemic formulations: Highest risk of interactions 3
2. Vaginal formulations: Moderate risk due to systemic absorption 2
3. Topical formulations: Lower but still clinically significant risk 2

Clinical Implications and Recommendations

1. For patients on warfarin:

   • Consider alternative antifungal treatments when possible
   • If miconazole must be used, reduce warfarin dose and monitor INR closely
   • Be aware that even topical miconazole can cause clinically significant interactions 2

2. For patients on other interacting medications:

   • Review complete medication list before prescribing miconazole
   • Consider therapeutic drug monitoring for medications with narrow therapeutic indices
   • Be particularly cautious with medications that affect cardiac conduction

3. Patient education:

   • Inform patients about potential interactions, especially those on anticoagulants
   • Advise patients to report any unusual bleeding or bruising immediately
   • Remind patients that over-the-counter antifungal products may contain miconazole

Common Pitfalls to Avoid

1. Overlooking topical formulations: Assuming topical miconazole doesn't cause systemic interactions is dangerous, as skin absorption can lead to significant drug interactions 1, 2

2. Failing to monitor after discontinuation: Drug interactions may persist for days after stopping miconazole due to its half-life

3. Missing over-the-counter use: Patients may not report using OTC miconazole products unless specifically asked

4. Underestimating oral gel absorption: Miconazole oral gel can be significantly absorbed and cause systemic effects 3

The evidence for miconazole drug interactions is robust, particularly for warfarin, with multiple case reports and pharmacokinetic studies confirming the clinical significance of these interactions. Healthcare providers should maintain a high index of suspicion for potential interactions when prescribing miconazole in any form.