Usage
Fluconazole + Ivermectin is a combination medication primarily used to treat fungal and parasitic infections. Fluconazole is an antifungal medication, while Ivermectin is an antiparasitic. This combination is effective against various fungal infections like candidiasis (e.g., oral thrush, vaginal yeast infections), cryptococcal meningitis, and some dermatophyte infections (e.g., ringworm, athlete’s foot). Ivermectin, on the other hand, is used against parasitic infections such as strongyloidiasis, onchocerciasis (river blindness), and scabies.
Pharmacological Classification:
- Fluconazole: Triazole antifungal
- Ivermectin: Avermectin antiparasitic
Mechanism of Action:
Fluconazole works by inhibiting the synthesis of ergosterol, a crucial component of fungal cell membranes, thereby disrupting fungal cell growth and replication. Ivermectin, in contrast, interferes with the nerve and muscle function of parasites by binding to glutamate-gated chloride channels, leading to paralysis and death of the parasites.
Alternate Names
While “Fluconazole + Ivermectin” is the generic name, the combination is marketed under various brand names such as Flumet Plus, Igcon Forte, and Alucon-IM. There aren’t widely recognized international variations for the combination name itself, although individual components may have other names regionally.
How It Works
Pharmacodynamics:
Fluconazole: Disrupts fungal cell membrane integrity by inhibiting ergosterol synthesis. This leads to fungal cell death and resolution of fungal infections.
Ivermectin: Increases the permeability of cell membranes to chloride ions in parasites and some insects, leading to hyperpolarization of nerve and muscle cells. This causes paralysis and death of the parasites.
Pharmacokinetics:
Fluconazole: Well-absorbed orally and intravenously. It is widely distributed throughout the body, achieving high concentrations in various tissues and fluids, including cerebrospinal fluid. Fluconazole is primarily eliminated by the kidneys, with a long half-life of approximately 30 hours. This allows for once-daily dosing in most cases.
Ivermectin: Well-absorbed orally. It is metabolized in the liver, primarily by CYP3A4 enzymes. Ivermectin is eliminated primarily in the feces, with a half-life of around 18 hours.
Mode of Action (Cellular/Molecular Level):
Fluconazole: Inhibits the fungal cytochrome P450 enzyme 14α-demethylase, which is essential for ergosterol biosynthesis.
Ivermectin: Binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells.
Elimination Pathways:
Fluconazole: Primarily renal excretion.
Ivermectin: Primarily hepatic metabolism and fecal excretion.
Dosage
The dosage of Fluconazole + Ivermectin depends on the specific infection being treated, patient age, weight, and renal function. It is crucial to follow the prescribing physician’s instructions precisely.
Standard Dosage
Adults:
- For fungal infections like vaginal candidiasis: A single dose of Fluconazole 150 mg + Ivermectin (dose depending on the co-infection).
- For other fungal infections: Fluconazole 50-400 mg once daily, combined with Ivermectin as needed for parasitic co-infection.
- For parasitic infections like onchocerciasis: Ivermectin 150 mcg/kg as a single dose, combined with Fluconazole if a fungal co-infection exists.
Children:
Dosage adjustments are necessary for children, usually based on weight. Consult a pediatrician or pediatric dosage guidelines for specific recommendations.
Special Cases:
- Elderly Patients: May require dose reductions, especially for Fluconazole, due to decreased renal function.
- Patients with Renal Impairment: Fluconazole dosage must be adjusted based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution is advised, and dosage adjustments might be necessary.
- Patients with Comorbid Conditions: Carefully consider other medical conditions (e.g., cardiac disorders, diabetes) and potential drug interactions.
Clinical Use Cases
The combination Fluconazole + Ivermectin is not typically used in settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. It is primarily indicated for specific fungal and parasitic infections in stable patients.
Dosage Adjustments
Dose modifications are essential in patients with renal or hepatic impairment, as well as in those with certain metabolic disorders or genetic variations affecting drug metabolism. Always adjust Fluconazole based on renal function. Consider drug interaction potentials when co-prescribing other medications.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Headache
- Dizziness
- Rash
- Abdominal pain
- Altered taste
Rare but Serious Side Effects:
- Hepatotoxicity (liver damage)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Severe skin reactions
- Seizures
- Cardiac arrhythmias
- Anaphylaxis
Long-Term Effects:
Prolonged use of high doses of Fluconazole, especially in patients with underlying liver disease, can lead to chronic liver damage. Long-term Ivermectin use can potentially cause neurological complications in some individuals.
Adverse Drug Reactions (ADR):
Any signs of severe skin reactions, liver dysfunction, cardiac arrhythmias, or anaphylaxis require immediate medical attention.
Contraindications
- Hypersensitivity to Fluconazole or Ivermectin
- Pregnancy (except in life-threatening fungal infections)
- Co-administration with drugs that prolong the QT interval (e.g., amiodarone) in patients with cardiac conditions
- Severe hepatic impairment
Drug Interactions
- Fluconazole interacts with numerous drugs metabolized by CYP enzymes (CYP3A4, CYP2C9, CYP2C19). It can increase the serum levels of warfarin, phenytoin, some benzodiazepines, and others.
- Ivermectin’s levels can be affected by CYP3A4 inducers or inhibitors.
- Avoid concomitant use with drugs that prolong the QT interval.
Pregnancy and Breastfeeding
- Fluconazole is generally contraindicated in pregnancy, especially during the first trimester, due to a potential risk of congenital malformations. However, it can be used in life-threatening fungal infections when the benefits outweigh the risks.
- Ivermectin’s safety in pregnancy is not well-established. Use with caution if necessary.
- Both Fluconazole and Ivermectin are present in breast milk. Breastfeeding is generally not recommended while taking these medications.
Drug Profile Summary
- Mechanism of Action: Fluconazole inhibits ergosterol synthesis; Ivermectin affects parasite nerve and muscle function.
- Side Effects: Nausea, vomiting, diarrhea, headache, dizziness, rash; rarely hepatotoxicity, severe skin reactions, cardiac arrhythmias.
- Contraindications: Hypersensitivity, pregnancy, severe hepatic impairment.
- Drug Interactions: CYP3A4 substrates, QT prolonging drugs.
- Pregnancy & Breastfeeding: Contraindicated or use with extreme caution.
- Dosage: Varies depending on infection and patient factors. Consult guidelines.
- Monitoring Parameters: Liver function tests, renal function tests, electrocardiogram (ECG) in patients with cardiac risk factors.
Popular Combinations
Fluconazole + Ivermectin is not a “popular” combination in the same way that some other drug combinations are. Its use is limited to situations where both a fungal and specific parasitic infection are present.
Precautions
- Assess liver and kidney function before and during treatment, especially with prolonged use.
- Monitor for signs of hypersensitivity reactions.
- Exercise caution in patients with pre-existing cardiac conditions.
- Avoid alcohol during treatment, as it may exacerbate side effects.
- Advise patients against driving or operating machinery if they experience dizziness or drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluconazole + Ivermectin?
A: The dosage varies greatly depending on the infections being treated, patient-specific factors, and the formulation available. Refer to the dosage section above and always consult local or international guidelines for specific recommendations.
Q2: What are the most common side effects?
A: Common side effects include nausea, vomiting, diarrhea, headache, dizziness, and rash.
Q3: Are there any serious side effects to be aware of?
A: Yes, rare but serious side effects include hepatotoxicity, severe skin reactions, cardiac arrhythmias, and seizures. Immediate medical attention is required if these occur.
Q4: Can this combination be used during pregnancy or breastfeeding?
A: Generally contraindicated. Fluconazole carries a risk of congenital malformations. Both drugs appear in breast milk. Consult a specialist for risk-benefit assessment in special situations.
Q5: What are the key drug interactions?
A: Fluconazole interacts with numerous drugs metabolized by CYP enzymes. Ivermectin can interact with CYP3A4 inducers/inhibitors. Caution is advised when co-administering with drugs that prolong the QT interval.
Q6: How does renal impairment affect dosing?
A: Fluconazole dosage needs to be adjusted in patients with renal impairment based on creatinine clearance.
Q7: What should I monitor in patients taking this combination?
A: Monitor liver function tests, renal function tests, and ECG (in patients with cardiac risk factors) as necessary. Observe for any signs of hypersensitivity or severe adverse reactions.
Q8: Is this combination effective against all fungal and parasitic infections?
A: No. Fluconazole is effective against specific fungal infections, primarily candidiasis and cryptococcal infections. Ivermectin is effective against certain parasitic infections, such as strongyloidiasis, onchocerciasis, and scabies, but not all.
Q9: Can this combination be used in children?
A: Yes, but dosage adjustments are necessary based on weight. Consult pediatric dosage guidelines or a specialist.
Q10: What precautions should I take when prescribing this medication?
A: Assess for contraindications and potential drug interactions. Evaluate liver and kidney function. Advise on potential side effects and precautions, including avoiding alcohol and operating machinery if dizziness or drowsiness occur.
