Terbinafine Hydrochloride

Antifungal, allylamine -one of the first antifungals of the allylamine class, discovered in 1974. It was approved for systemic use in the UK in 1991, and for topical use in the USA in 1992.

Terbinafine is an antifungal effective against Dermatophytes, Aspergillus sp., and Candida and Pityrosporum yeasts. Terbinafine is only fungistatic against Candida, however cure is possible after 2-4 weeks of treatment (-).
It is available in systemic and topical formulations. Systemic treatment is usually reserved for infections of the nails, extensive cutaneous infections or those, which have not responded to topical therapy.

Trade Name:

• Lamisil*   Novartis
• Lamisil DermGel*   Novartis
• Lamisil AT*   Novartis

Dosage Types;

• Topical: Cream: Terbinafine hydrochloride 1% *
  Lamisil* and Lamisil AT
• Solution: Terbinafine hydrochloride Lamisil
• Oral: Tablets: Terbinafine hydrochloride tablets 250 mg Lamisil*

Therapeutic Regimen

Patient Monitoring

Liver function tests are recommended before treatment and periodically during therapy, in patients with hepatic impairment, alcoholism, and those taking hepatotoxic drugs.

• Local cutaneous effects may include mild burning, irritation, and erythema.
• Cutaneous effects may include hypersensitivity reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Gastrointestinal effects may include nausea, dyspepsia, stomach pain, reversible loss of taste and hepatitis.
• Hematologic effects may include neutropenia and pancytopenia.

FDA Pregnancy Category B
Human tests have not been completed, but animal testing has not shown any adverse fetal effects. Terbinafine is distributed in the breast milk. Treatment during pregnancy and lactation is not recommended.

Major Drug Interactions
Concurrent use of terbinafine with caffeine, theophylline and naphtylline may increase their toxicity; alcohol and hepatotoxic medications may increase the risk of liver damage; drugs that induce the cytochrome P-450 system may increase the clearance of terbinafine; drugs that inhibit the cytochrome P-450 system may decrease the clearance of terbinafine.

Mechanism of Action / Pharmacokinetics

Terbinafine interferes with fungal ergosterol synthesis by inhibiting the enzyme squalene epoxide in the fungal cell membrane.
This leads to fungal cell death by disruption of fungal membrane function and cell wall synthesis. The oral dose is well absorbed from the gastrointestinal tract, and is extensively distributed to the hair follicle, nail plate and sebum-rich skin.
It can be detected in nail clippings three weeks after the initiation of therapy.

Terbinafine undergoes first pass metabolism, involving a small percentage of the total hepatic P450 capacity. Its elimination is primarily renal.
Topical terbinafine is minimally absorbed, less than 5% is detected systemically. Topical terbinafine concentrates in the lipophilic stratum corneum

General References

Elewski BE: Tinea capitis: A current perspective. Jour. Am. Acad. Derm. 2000: 42: 1-20

Gupta AK, Shear NH: Terbinafine: An Update. Jour. Am. Acad. Derm. 1997: 37: 979-988

Caceres-Rios H, Rueda M, Ballona R, et al: Comparison of terbinafine and Griseofulvin in the treatment of tinea capitis. Jour. Am. Acad. Derm. 2000: 42: 80-84

Evans EGV, Sigurgeirsson B, LIONS Study Group: Double blind randomised study of continuous terbinafine compared with intermittent Itraconazole in treatment of toenail onychomycosis. Br. Med. Jour. 1999: 318: 1031-1035

Krafchik B: The Clinical Efficacy of Terbinafine in the treatment of Tinea Capitis. Rev. Contemp. Pharmacother. 1997 ; 8 ; 313-324

Zaias N, Serrano L: the successful treatment of finger trichophytum rubrum onychomycosis with oral terbinafine. Clin. Exp. Derm. 1989: 14: 120-123 Gupta AK, Shear NH: A risk-benefit assessment of newer oral antifungal agents used to treat onychomycosis. Drug Safety: 2000: 22: 33-52

Gupta AK, Lynde CW, Lauzon GJ, et al: Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature. Br. Jour. Derm. 1998: 138: 529-532

Ornstein DL, Ely P: Reversible agranulocytosis associated with oral terbinafine for onychomycosis. Jour. Am. Acad. Derm. 1998: 39 (6): 1023-1024

Shapiro M, Li L-J, Miller J: Terbinafine-induced neutropenia. Br. Jour. Derm. 1999: 140: 1169-1199

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