Fluconazole (Diflucan®) versus Terbinafine (Lamisil®)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Difference between Fluconazole and Terbinafine

  • Both Fluconazole (Diflucan®) and Terbinafine (Lamisil®) are potent antifungal medications.
  • Fluconazole is included in WHO list of essential medicines in section Antifungal medicines.
  • Terbinafine is included in WHO list of essential medicines in section in Dermatological (topical) Antifungal medicines.
  • Fluconazole is a first-line therapy for many candidal infections, including vulvovaginal yeast infection (vaginal thrush), candida cystitis, invasive candidiasis 3.
  • Terbinafine is a first-line therapy for dermatophyte onychomycosis (fungal nail infection)4.
  • Fluconazole achieves very high concentrations in the urine, so this antifungal drug is particularly effective for fungal urinary tract infections8.

Table 1. Comparison of Fluconazole and Terbinafine

Fluconazole Terbinafine
Brand names
• Diflucan® • Lamisil®
Diflucan Pfizer Lamisil Novartis
Drug class
• Azole antifungal agent • Allylamine antifungal agent
Dose formulations
• Tablets
• Oral suspension
• Injected solution
• Tablets
• Topical cream
• Topical solution
Legal status
• Rx only • OTC (topical)
• Rx (oral)
FDA-approved indications
• Vaginal candidiasis (vaginal yeast infections due to Candida)
• Systemic Candida infections
• Oropharyngeal Candidiasis
• Esophageal Candidiasis
• Cryptococcal meningitis
• Oral
• Fingernail onychomycosis
• Toenail onychomycosis
• Severe tineal skin infections unresponsive to topical therapy (in Canada)

• Tinea versicolor (pityriasis)
• Tinea pedis (athlete’s foot)
• Tinea corporis (ringworm)
• Tinea cruris (jock itch)
"Off-label" uses
• Alternative treatment choice for dermatophyte onychomycosis in persons unable to tolerate terbinafine or itraconazole4
• Cryptococcal lung diseas
• Onychomycosis 5
• Tinea corporis (ringworm)6
• Tinea cruris 6
• Tinea pedis 6
• Tinea versicolor
• Ductal thrush in lactating women 7
• Non-dermatophyte nail infections (Scopulariopsis, Aspergillus, species, Fusarium species)
• Oral antifungal therapy for severe or extensive tinea infections
• Tinea capitis (scalp ringworm)
Antifungal spectrum
• Fluconazole is active against common dermatophytes, Candida species and some nondermatophytic molds. • Terbinafine has excellent fungicidal activity against many dermatophytes.
• However, terbinafine is notably less active against nondermatophytes, including yeasts.
Mechanism of action
• Fluconazole is mainly fungistatic.
• Fluconazole interferes with fungal cytochrome P450 activity, decreasing ergosterol synthesis (important sterol in fungal cell membrane) and inhibiting cell membrane formation. This leads to inhibition of cell growth and replication.
• Terbinafine is mainly fungicidal.
• Terbinafine blocks biosynthesis of fungal sterol by inhibition of squalene epoxidase, a complex enzyme system in the fungal cell membrane.
• 30 hours • 36 hours
Oral bioavailability
• 90% • 90%
Metabolism, Elimination
• Fluconazole has almost complete oral bioavailability, and undergoes only negligible hepatic metabolism.
• Fluconazole is excreted primarily through the kidneys in unchanged form.
• Terbinafine is extensively metabolized by CYP isoenzymes (including CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19).
• All terbinafine metabolites are inactive and without antifungal activity.
• About 70% of terbinafine is eliminated in the urine.
• Hypersensitivity to fluconazole
• Coadministration of fluconazole with medications known to prolong the QT interval and which are metabolized via CYP3A4
• Hypersensitivity to terbinafine
• Chronic or active liver disease
Side effects
• Headache
• Nausea
• Abdominal pain
• Rash
• Vomiting
• Diarrhea
• Headache
• Diarrhea
• Nausea
• Dyspepsia
• Rash
• Itching
• Abnormal liver enzyme levels
Pregnancy category
• D
• C (for single 150 mg table)
• C
Drug Interactions
• Both medications have important drug interactions.
• With terbinafine drugs interactions is a less problem than with fluconazole.

Fluconazole vs Terbinafine for Onychomycosis

Onychomycoses are fungal infections of the hand and foot nails, caused by dermatophytes, yeasts and molds. These conditions are difficult to treat, and recurrences are frequent.

Fluconazole is less effective than terbinafine for nail fungal infections. However, fluconazole may be preferred in patients unable to take terbinafine or other oral antifungals due to the dosing regimen, side effects profile, or drug interactions.

Results of clinical trial comparing fluconazole and terbinafine for onychomycosis9. Fluconazole Terbinafine
Dosage regimen 150 mg once weekly for 12 weeks 150 mg once weekly for 24 weeks 250 mg daily for 12 weeks
Mycological cure rate at completion of the study (week 60) 51% 49% 89%
The length of healthy nail increased until week 24 increased until week 36 continued to increase at the last visit (week 60)
Complete clinical cure of the affected nail at week 60 21% 32% 67%

Fluconazole vs Terbinafine for Tinea Corporis (Ringworm)

Tinea corporis (ringworm) is a superficial dermatophyte infection of the glabrous skin (e.g. arms, legs, trunk). Ringworm is characterized by ring-shaped, scaly and itchy lesions.

Results of the study comparing efficacy of terbinafine and fluconazole in for tinea corporis 10. Fluconazole Terbinafine
Dosage regimen 150 mg once weekly for 4 weeks 250 mg daily for 4 weeks
Clinical response rate at week 4 82 % 92,9 %


  • 1. Prescribing Information for Fluconazole (Diflucan®) PDF
  • 2. Prescribing Information for Terbinafine (Lamisil®) PDF
  • 3. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG, Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):e1-50. PubMed, Oxford University Press
  • 4. Ameen M, Lear JT, Madan V, Mohd Mustapa MF, Richardson M. British Association of Dermatologists’ guidelines for the management of onychomycosis 2014. Br J Dermatol. 2014 Nov. 171(5):937-58.
  • 5. Arca E, Taştan HB, Akar A, Kurumlu Z, Gür AR. An open, randomized, comparative study of oral fluconazole, itraconazole and terbinafine therapy in onychomycosis. J Dermatolog Treat. 2002 Mar;13(1):3-9.
  • 6. Montero-Gei F, Perera A. Therapy with fluconazole for tinea corporis, tinea cruris, and tinea pedis. Clin Infect Dis. 1992 Mar;14 Suppl 1:S77-81.
  • 7. Moorhead AM, Amir LH, O'Brien PW, Wong S. A prospective study of fluconazole treatment for breast and nipple thrush. Breastfeed Rev. 2011 Nov;19(3):25-9.
  • 8. William J. Steinbach, Christopher C. Dvorak, in Principles and Practice of Pediatric Infectious Diseases (4th Edition), 2012
  • 9. Havu V, Heikkilä H, Kuokkanen K, Nuutinen M, Rantanen T, Saari S, Stubb S, Suhonen R, Turjanmaa K. A. double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis. Br J Dermatol. 2000 Jan;142(1):97-102.
  • 10. Kumar, A., Budania, N., Sharma, P., Singh, M., A comparative study of mycological efficacy of terbinafine and fluconazole in patients of tinea corporis. IJBR 2013 4(11): 7-10.

Published: December 03, 2018
Last updated: December 03, 2018


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