1. Clinical Overview
A fixed-dose combination (FDC) tablet containing a triazole antifungal (Fluconazole) and an anthelmintic/antiparasitic agent (Ivermectin). This combination is primarily used in the Indian context for the treatment of mixed fungal and parasitic skin infections, particularly in cases of suspected or confirmed co-infection where superficial dermatophytosis (tinea) is complicated by concurrent parasitic infestations like scabies or strongyloidiasis. It is important to note that this specific FDC is not approved by major international regulatory bodies like the US FDA or the European EMA. Its use in India is based on a clinical rationale for addressing polymicrobial skin conditions, but it should be prescribed judiciously.
| Onset | Duration | Bioavailability |
|---|---|---|
| Fluconazole: Clinical improvement in fungal infections typically seen within 3-5 days. Ivermectin: Peak plasma concentration in 4 hours; scabicidal effect begins within days, with pruritus relief potentially within 1 week. | Fluconazole: Antifungal activity in plasma and tissues can persist for several days post-dose due to long half-life. Ivermectin: A single dose is often sufficient for scabies, with effects lasting weeks. | Fluconazole: >90% (oral). Ivermectin: Approximately 50% (oral). |
2. Mechanism of Action
Fluconazole inhibits fungal cytochrome P450 enzyme 14α-demethylase, disrupting ergosterol synthesis (a critical component of fungal cell membranes), leading to increased membrane permeability and inhibition of fungal growth. Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, causing increased cell permeability to chloride ions, hyperpolarization, paralysis, and death of the parasite. It may also interact with other ligand-gated chloride channels.
3. Indications & Uses
- Mixed dermatological infections with confirmed or strongly suspected co-existing superficial fungal infection (e.g., tinea corporis, tinea cruris, tinea pedis) and parasitic infestation (e.g., scabies).
- Cutaneous larva migrans (creeping eruption) with secondary fungal infection.
- Strongyloidiasis (intestinal) with concurrent cutaneous fungal manifestations.
4. Dosage & Administration
Adult Dosage: One tablet (Fluconazole 150mg + Ivermectin 6mg) as a single dose. May be repeated after 1-2 weeks for scabies if live mites are still present. For fungal infections, a single 150mg fluconazole dose is often sufficient for vaginal candidiasis; for tinea, longer courses are typical, making this FDC's single dose potentially suboptimal for fungus alone.
Administration: Take orally with a full glass of water. Can be taken with or without food (food increases ivermectin bioavailability slightly). For scabies, all household and close physical contacts should be treated simultaneously. Topical scabicidal agents and environmental decontamination of fomites are also recommended.
5. Side Effects
Common side effects may include:
- Headache
- Nausea
- Abdominal pain
- Diarrhea
- Dizziness
- Fatigue
- Skin rash or itching (may be due to dying parasites - Mazzotti-like reaction)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Rifampicin | Decreases fluconazole plasma levels by increasing metabolism. May reduce efficacy. | Major |
| Warfarin | Fluconazole inhibits metabolism, increasing anticoagulant effect and risk of bleeding. Monitor INR closely. | Major |
| Phenytoin | Fluconazole increases phenytoin levels. Phenytoin may decrease fluconazole levels. Monitor phenytoin levels. | Major |
| Cyclosporine, Tacrolimus | Fluconazole inhibits metabolism, increasing nephrotoxic immunosuppressant levels. Monitor serum creatinine and drug levels. | Major |
| Sulfonylureas (e.g., Glipizide) | Fluconazole can increase hypoglycemic effect. Monitor blood glucose. | Moderate |
| Theophylline | Fluconazole may increase theophylline levels. Monitor for toxicity. | Moderate |
| Midazolam, Triazolam | Fluconazole increases benzodiazepine levels and sedation. Dose reduction may be needed. | Moderate |
| Statins (Metabolized by CYP3A4 e.g., Atorvastatin) | Fluconazole increases statin levels, raising risk of myopathy/rhabdomyolysis. | Moderate |
| CYP3A4 Inducers (e.g., Carbamazepine, St. John's Wort) | May decrease ivermectin levels. | Moderate |
| CYP3A4 Inhibitors (e.g., Clarithromycin, Itraconazole) | May increase ivermectin levels and risk of neurotoxicity. | Moderate |
7. Patient Counselling
- Do take the tablet as a single dose, with water.
- Do inform your doctor about all other medicines, vitamins, and herbal products you are taking.
- Do treat all household members for scabies simultaneously if prescribed for that indication.
- Do wash all clothing, bedding, and towels in hot water and dry on high heat if treating scabies.
- Don't take a second dose unless specifically instructed by your doctor.
- Don't share this medication with others.
- Don't use it for vaginal yeast infection unless specifically diagnosed with a co-existing skin parasite.
8. Toxicology & Storage
Overdose: Fluconazole: May lead to paranoid ideation, auditory/visual hallucinations, paranoid behavior, QTc prolongation. Ivermectin: CNS depression, dizziness, sedation, vomiting, mydriasis, ataxia, tremors, seizures (especially with concomitant CYP3A4 inhibitors or disrupted blood-brain barrier). Combined overdose could present with severe GI upset, neuropsychiatric symptoms, and cardiac effects.
Storage: Store below 30°C. Protect from light and moisture. Keep in the original blister pack until use. Keep out of reach of children.