Fluconazole: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Malaysia prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous
Cryptococcal meningitis

Adult: As treatment: 400 mg on Day 1, followed by 200-400 mg once daily; may increase to 800 mg daily if needed. Duration of treatment: Minimum of 6-8 weeks. For prevention of relapse after primary course of treatment for cryptococcal meningitis in patients with AIDS: 200 mg once daily. Doses are given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: 6-12 mg/kg once daily, depending on the severity of infection. For prevention of relapse in patients with AIDS: 6 mg/kg once daily. Doses are given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Intravenous
Oesophageal candidiasis

Adult: 50 mg once daily, may increase to 100 mg once daily if needed. Duration of treatment: 14-30 days. Alternatively, an initial dose of 200 mg on Day 1, followed by 100 mg once daily; may increase up to 400 mg daily. Duration of treatment: Minimum of 3 weeks and for at least 2 weeks after symptom resolution. Doses are given via infusion. Dosage and infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: 6 mg/kg on Day 1, followed by 3 mg/kg once daily. Doses are given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Intravenous
Oropharyngeal candidiasis

Adult: 50-100 mg once daily for 7-14 days. Alternatively, an initial dose of 200 mg on Day 1, followed by 100 mg once daily for at least 2 weeks. Doses are given via infusion. Dosage and infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: 6 mg/kg on Day 1, followed by 3 mg/kg once daily. Doses are given via infusion. Dosage and infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Intravenous
Candiduria

Adult: 50 mg once daily, may increase to 100 mg once daily if needed. Duration of treatment: 14-30 days. Doses are given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Intravenous
Chronic atrophic candidiasis

Adult: In cases associated with dentures: 50 mg once daily for 14 days given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Intravenous
Prophylaxis of candidiasis

Adult: In patients at high risk of systemic infections (e.g. due to occurring potentiated or prolonged neutropenic phase): 400 mg once daily. Initiate treatment several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count has increased to >1,000 cells/mm³. Doses are given via infusion. Treatment and infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: In immunocompromised patients: 3-12 mg/kg once daily, depending on the extent and duration of neutropenia. Doses are given via infusion. Treatment and infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Intravenous
Systemic candidiasis

Adult: 400 mg on Day 1, followed by 200-400 mg once daily. Duration of treatment is based on clinical response. Doses are given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: 6-12 mg/kg once daily, depending on the severity of the infection. Doses are given via infusion. Infusion rate recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Oral
Cryptococcal meningitis

Adult: As treatment: 400 mg on Day 1, followed by 200-400 mg once daily. Duration of treatment: Minimum of 6-8 weeks. For prevention of relapse after primary course of treatment for cryptococcal meningitis in patients with AIDS: 100-200 mg once daily.
Child: 6-12 mg/kg once daily, depending on the severity of the infection. For prevention of relapse in patients with AIDS: 6 mg/kg once daily.

Oral
Oropharyngeal candidiasis

Adult: 50 mg once daily, may increase to 100 mg once daily if needed. Duration of treatment: 7-14 days. Alternatively, an initial dose of 200 mg on Day 1, followed by 100 mg once daily for at least 14 days.
Child: 6 mg/kg on Day 1, followed by 3 mg/kg once daily. Max: 400 mg daily.

Oral
Oesophageal candidiasis

Adult: 50 mg once daily, may increase to 100 mg once daily if needed. Duration of treatment: 14-30 days. Alternatively, an initial dose of 200 mg on Day 1, followed by 100 mg once daily; may increase up to 400 mg daily if needed. Duration of treatment: Minimum of 3 weeks and for at least 2 weeks after symptom resolution. Dosage recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: 6 mg/kg on Day 1, followed by 3 mg/kg once daily; may increase up to 12 mg/kg daily if needed. Duration of treatment: Minimum of 3 weeks and for at least 2 weeks after symptom resolution. Dosage recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Oral
Non-invasive bronchopulmonary candidiasis

Adult: 50 mg once daily, may increase to 100 mg once daily if needed. Duration of treatment: 14-30 days.

Oral
Chronic atrophic candidiasis

Adult: In cases associated with dentures: 50 mg once daily for 14 days.

Oral
Cutaneous candidiasis, Tinea corporis, Tinea cruris, Tinea pedis

Adult: 50 mg once daily or 150 mg once weekly. Duration of treatment: 2-4 weeks (up to 6 weeks in tinea pedis).

Oral
Systemic candidiasis

Adult: 400 mg on Day 1, followed by 200-400 mg once daily. Duration of treatment is based on clinical response.
Child: 6-12 mg/kg once daily, depending on the severity of the infection.

Oral
Pityriasis versicolor

Adult: 50 mg once daily or 150 mg once weekly for 2-4 weeks. Alternatively, 300 mg once weekly for 2 weeks.

Oral
Candidal balanitis

Adult: 150 mg as a single dose.
Child: ≥16 years Same as adult dose.

Oral
Candiduria

Adult: 50 mg once daily, may increase to 100 mg once daily if needed. Duration of treatment: 14-30 days.

Oral
Vaginal candidiasis

Adult: 150 mg as a single dose. For recurrent cases: 150 mg 72 hourly for 3 doses, then 150 mg once weekly for 6 months.

Oral
Prophylaxis of candidiasis

Adult: In patients at high risk of systemic infections (e.g. due to occurring potentiated or prolonged neutropenic phase): 400 mg once daily. Initiate treatment several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count has increased to >1,000 cells/mm³. Dosage or treatment recommendations may vary among countries and individual products (refer to specific country or product guidelines).
Child: In immunocompromised patients: 3-12 mg/kg once daily, depending on the extent and duration of neutropenia. Treatment recommendations may vary among countries and individual products (refer to specific country or product guidelines).

Renal Impairment

Patient on regular haemodialysis: 50-400 mg as an initial loading dose, followed by 100% of the recommended daily dose after each haemodialysis session.

CrCl (mL/min)	Dosage
≤50	50-400 mg as an initial loading dose, followed by 50% of the recommended daily dose.

Administration

May be taken with or without food.

Reconstitution

Powder for oral susp: Reconstitute with the appropriate volume of water as specified on the container and shake vigorously until suspended.

Contraindications

Hypersensitivity. Concomitant use with drugs known to prolong QT interval and are metabolised by CYP3A4 isoenzyme (e.g. cisapride, astemizole, amiodarone, erythromycin, pimozide, quinidine). Concomitant use with terfenadine in patients receiving fluconazole at multiple doses of ≥400 mg daily.

Special Precautions

Patient with proarrhythmic condition (e.g. congenital or documented acquired QT prolongation, structural heart disease, sinus bradycardia, existing symptomatic arrhythmias, electrolyte disturbances [e.g. hypokalaemia, hypomagnesaemia, hypocalcaemia]), serious underlying disease (e.g. AIDS, cancer). Renal and hepatic impairment. Neonates and children. Pregnancy and lactation.

Adverse Reactions

Significant: Adrenal insufficiency (reversible). Rarely, anaphylactic reactions, QT prolongation on ECG, torsades de pointes.
Blood and lymphatic system disorders: Anaemia.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, taste perversion, constipation, dry mouth, flatulence, dyspepsia.
General disorders and administration site conditions: Malaise, fatigue, fever, asthenia.
Investigations: Increased ALT, AST or alkaline phosphatase.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Myalgia.
Nervous system disorders: Headache, dizziness, seizures, paraesthesia.
Psychiatric disorders: Insomnia, somnolence.
Skin and subcutaneous tissue disorders: Increased sweating, rash, fixed drug eruption, alopecia, pruritus, urticaria.
Potentially Fatal: Rarely, serious hepatotoxicity, severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms).

Pregnancy Category (US FDA)

PO: C (For a single dose of 150 mg for vaginal candidiasis.), D (For use in indications other than vaginal candidiasis.); Parenteral: D

Patient Counseling Information

This drug may cause dizziness or seizures, if affected, do not drive or operate machinery.

Monitoring Parameters

Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to drug resistance risks. Monitor LFTs (e.g. AST, ALT, alkaline phosphatase), renal function and serum K periodically. Assess for rash, abdominal pain, and signs and symptoms of hepatic injury.

Overdosage

Symptoms: Hallucination and paranoid behaviour. Management: Symptomatic and supportive treatment. Perform gastric lavage if needed. Haemodialysis for 3 hours may decrease the plasma levels by approx 50%.

Drug Interactions

Increased plasma concentrations with hydrochlorothiazide. Decreased serum concentrations with rifampicin. May increase the plasma concentrations of drugs metabolised by CYP3A4, CYP2C9, and CYP2C19 (e.g. halofantrine, amitriptyline, nortriptyline, midazolam, triazolam, amlodipine, verapamil, felodipine, carbamazepine, celecoxib, flurbiprofen, ciclosporin, alfentanil, fentanyl, methadone, oral estrogen-progestin contraceptives, phenytoin, rifabutin, saquinavir, glibenclamide, glipizide, tolbutamide, everolimus, tacrolimus, sirolimus, theophylline, voriconazole, zidovudine, olaparib, ivacaftor, tolvaptan, tofacitinib, abrocitinib, lemborexant, lurasidone, vincristine, vinblastine). Increased prothrombin time with anticoagulants (e.g. warfarin). Increased risk of elevated serum bilirubin and serum creatinine with cyclophosphamide. Increased risk of myopathy and rhabdomyolysis with HMG-CoA reductase inhibitors metabolised by CYP3A4 (e.g. atorvastatin, simvastatin) or CYP2C9 (e.g. fluvastatin). Inhibits the metabolism of losartan to its active metabolite. May increase the risk of CNS-related adverse effects (e.g. pseudotumour cerebri) with tretinoin.
Potentially Fatal: May increase the plasma levels of cisapride, astemizole, pimozide, quinidine, amiodarone, and erythromycin, thus increasing the risk of cardiac effects (e.g. QT interval prolongation, torsades de pointes). Fluconazole (at doses ≥400 mg daily) significantly increases the plasma levels of terfenadine.

Action

Description:
Mechanism of Action: Fluconazole is a triazole derivative antifungal agent that inhibits the CYP450-mediated 14-α-lanosterol demethylation in susceptible fungi. This results in reduced ergosterol synthesis and inhibition of fungal cell membrane formation.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: >90%. Time to peak plasma concentration: 1-2 hours (oral).
Distribution: Widely distributed into body tissues and fluids. Enters breast milk. Volume of distribution: Approx 0.6 L/kg. Plasma protein binding: 11-12%.
Excretion: Via urine (approx 80% as unchanged drug, approx 11% as metabolites). Elimination half-life: Approx 30 hours (range: 20-50 hours).

Chemical Structure

Storage

Tab/Cap/Powder for oral susp: Store below 30°C. Reconstituted oral susp/Solution for IV infusion: Store between 5-30°C. Do not freeze. Storage recommendations may vary among individual products. Refer to specific product guidelines.

MIMS Class

Antifungals

ATC Classification

J02AC01 - fluconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.

References

Galgiani JN, Ampel NM, Blair JE et al. 2016 Infectious Disease Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clinical Infectious Disease. 2016 Sep;63(6):e112-146. doi: 10.1093/cid/ciw360. Accessed 02/05/2023. PMID: 27470238

Anon. Fluconazole (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/05/2023.

Anon. Fluconazole. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/05/2023.

Anon. Fluconazole. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/05/2023.

Apo-Fluconazole Tablet (Pharmaforte [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/05/2023.

Baxter Healthcare Ltd. Fluconazole-Baxter 0.2% w/v (2 mg/mL) Solution for Infusion data sheet 22 February 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 02/05/2023.

Buckingham R (ed). Fluconazole. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/05/2023.

Canesten Thrush Oral Capsule 150 mg (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2023.

Diflucan Capsule and Solution for Intravenous Infusion (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/05/2023.

Diflucan Tablet; Powder, for Suspension (Roerig). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2023.

Fluconazole 2 mg/mL Solution for Infusion (B. Braun Melsungen AG). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2023.

Fluconazole 200 mg Capsules (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2023.

Fluconazole 50 mg/5 mL Powder for Oral Suspension (Genus Pharmaceuticals Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/05/2023.

Fluconazole Injection, Solution (Baxter Healthcare Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/05/2023.

Fluconazole Kabi 2 mg/mL Solution for Infusion (Fresenius Kabi Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/05/2023.

Fluconazole. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 02/05/2023.

Johnson & Johnson (New Zealand) Limited. Diflucan One Capsule 150 mg data sheet 7 June 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 02/05/2023.

Joint Formulary Committee. Fluconazole. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/05/2023.

Paediatric Formulary Committee. Fluconazole. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 02/05/2023.

Pfizer New Zealand Limited. Diflucan Powder for Oral Suspension, Capsules, Solution for Infusion data sheet 17 December 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 02/05/2023.

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