Are there any contraindications with ivermectin and fluconazole (antifungal medication)?

Ivermectin and Fluconazole Combination Safety

There are no absolute contraindications to combining ivermectin and fluconazole, and these medications can be used together safely in clinical practice. Neither drug has a documented pharmacokinetic or pharmacodynamic interaction that would preclude their concurrent use.

Key Safety Considerations

Drug Interaction Profile

• Fluconazole primarily inhibits CYP2C9, CYP2C19, and to a lesser extent CYP3A4 enzymes 1, 2
• Ivermectin is metabolized by CYP3A4, but the degree of fluconazole's inhibition of this pathway is modest and has not been shown to cause clinically significant interactions with ivermectin in practice 1
• The retrospective study of 150 antifungal treatment episodes identified drug-drug interactions primarily with amphotericin B (81%), fluconazole (17.2%), but none specifically involving ivermectin 3

Monitoring Recommendations When Using Both Drugs

Hepatic monitoring is the primary concern when combining these agents:

• Obtain baseline liver function tests before initiating therapy 1
• Monitor transaminases at 2 weeks, 4 weeks, then every 3 months during prolonged fluconazole therapy 1
• Fluconazole causes asymptomatic transaminase elevations in 1-13% of patients, with rare cases of hepatitis 1

Renal function assessment should be performed:

• Check baseline creatinine clearance, as fluconazole requires dose adjustment when CrCl <50 mL/min (reduce dose by 50%) 4, 1
• Ivermectin does not require renal dose adjustment but should be used cautiously in severe renal impairment

Gastrointestinal effects may be additive:

• Both drugs can cause nausea and vomiting 1
• High-dose fluconazole (≥800 mg/day) increases GI toxicity risk 4

Cardiac Considerations

QTc prolongation monitoring is relevant for fluconazole but not ivermectin:

• Fluconazole can prolong QTc interval, particularly when combined with other QT-prolonging medications 2
• Obtain baseline ECG if cardiac risk factors are present 2
• Check and correct electrolytes (potassium >4 mEq/dL, magnesium >1.8 mg/dL) before starting fluconazole 2
• Ivermectin does not cause QTc prolongation and does not contribute to this risk

Clinical Context for Combined Use

The most common scenario requiring both medications would be:

• Parasitic infection (ivermectin indication) concurrent with fungal infection (fluconazole indication) 5, 6, 7
• Immunocompromised patients may require treatment for both parasitic and fungal infections simultaneously 6

Common Pitfalls to Avoid

• Do not assume fluconazole is free of drug interactions—it definitively inhibits multiple CYP enzymes, though the clinical impact on ivermectin is minimal 1, 2
• Do not overlook baseline liver function testing—both drugs can cause hepatotoxicity, though this is more common with fluconazole 1
• Do not ignore electrolyte monitoring if using high-dose fluconazole, as hypokalemia increases cardiac arrhythmia risk 2

Special Populations

Pregnancy: Fluconazole at high doses (400-800 mg/day) during the first trimester is associated with congenital abnormalities and should be avoided; ivermectin safety in pregnancy is less well-established 8

Immunocompromised patients: Both drugs are commonly used in this population, and combination therapy poses no additional contraindication beyond standard monitoring 6, 3