Lamisil scientific update |
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J Huazhong Univ Sci Technolog Med Sci.
Chen S, Li S, Liu Z, Wu Y, Tu Y, Li J.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology .
Comparison of the effects of three different anti-fungus drugs on Candida albicans of murine vaginal mucosa.
To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and
intraconazole) in the treatment of experimental vaginitis caused by Candida albicans (C. albicans) in mice, the
fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans
after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then
respectively treated with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden of the
fungus in the vaginal lavage fluids in the mice of the different groups was measured dynamically at different time
points after the beginning of the drug treatment. The fungal burdens in the vaginal lavage fluids taken at
different time points from the mice treated with terbinafine were significantly higher than those taken at
corresponding time points from mice treated with fluconazole or itraconazole (P<0.01). The fungal burdens in the
vaginal lavage fluids taken from mice 1 week after the beginning of the treatment with terbinafine remained at a
relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd
day of the treatment from mice treated with itraconazole or fluconazole group and the fungal burden on the 3rd day
of the treatment in these mice were at a very low level, suggesting that fluconazole or itraconazole were highly
effective for the treatment. However, the difference in the therapeutic effect between the two drugs was not
significant (P>0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of
fungal vaginitis caused by C. albicans in mice.
Scand J Infect Dis. 2007;39(1):87-90.
Bhat SV, Paterson DL, Rinaldi MG, Veldkamp PJ.
Division of Infectious Diseases, The University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Scedosporium prolificans brain abscess in a patient with chronic granulomatous disease: successful combination therapy with voriconazole and terbinafine.
A patient with chronic granulomatous disease developed brain abscesses with Scedosporium prolificans. In vitro
susceptibility revealed a synergistic effect of terbinafine and voriconazole. He received therapy with both these
antifungals which resulted in disappearance of the brain abscesses. This is the first reported cure of a CNS S.
prolificans infection in an immunocompromised host.
Ann Pharmacother. 2007 May;41(5):880-4.
Paredes AH, Lewis JH.
Department of Internal Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Terbinafine-induced acute autoimmune hepatitis in the setting of hepatitis B virus infection.
OBJECTIVE: To report a case of terbinafine-induced autoimmune hepatitis in a patient with chronic hepatitis B
infection. CASE SUMMARY: A 57-year-old Taiwanese male with chronic hepatitis B virus (HBV) began an oral regimen of
terbinafine 250 mg once daily for dermatophyte toenail onychomycosis, despite the manufacturer's recommendation not
to use the drug in patients with liver dysfunction. The patient's liver enzyme levels were within normal limits at
initiation of therapy. Immediately prior to concluding the 12 week treatment course, he became anorexic with
malaise and subsequently developed ascites and jaundice. After a visit to an outside emergency department and
positively trending liver function test levels, he was referred to our liver clinic. The patient was taking no
other medications or herbal supplements, did not drink alcohol, and did not appear to suffer a flare of HBV
infection. The diagnosis was supported by the presence of transient autoantibodies and a liver biopsy consistent
with acute autoimmune drug injury. Three weeks after terbinafine was discontinued, peak levels of aspartate
aminotransferase (1282 IU/L), alanine aminotransferase (1044 IU/L), and bilirubin (5.9 mg/dL) were noted; his
platelet level had decreased to 77 x 10(3)/mm3. He was treated with supportive care that included vitamin K for
coagulopathy, diuretics for ascites, and adefovir to prevent hepatitis B exacerbation. The patient's liver function
studies began to normalize 6 weeks after terbinafine was discontinued. DISCUSSION: Terbinafine-induced
hepatobiliary dysfunction, due to hepatocellular injury, cholestasis, or mixed form, has been reported, but this is
the first case of autoimmune hepatitis supported by serologic, biochemical, and biopsy results. Use of the Naranjo
probability scale revealed a probable relationship between the patient's hepatitis and terbinafine. Furthermore,
the Roussel Uclaf Causality Assessment Method, a scoring system that specifically assesses the likelihood of
drug-induced elevated levels of liver-associated enzymes, also supported a probable relationship. The pathogenesis
of most drug-induced autoimmune hepatitis remains speculative, likely involving hapten-carrier complex and the
cytochrome P450 isoenzymes. In this patient, his chronic HBV carrier state may have predisposed him to this
autoimmune reaction. CONCLUSIONS: Healthcare practitioners should heed the manufacturer's warning that terbinafine
not be used in patients with underlying hepatic disease.
Therapie. 2006 May-Jun;61(3):251-4.
Dupont B.
Maladies Infectieuses et Tropicales, Universite Paris 5, Hopital Necker-Enfants Malades, Paris, France.
[Use of topical antifungal agents][Article in French]
Topical antifungal agents are not absorbed when given orally. They act by direct contact on the fungus, this type of action requires the simultaneous presence of antifungal and fungus for a minimum of time. There are a large number of compounds belonging to different families of antifungals: polyens, azoles, allylamine and morpholine and antiseptic substances. The treatment of oropharyngeal candidiasis is based on topical antifungal agents: amphotericin B or nystatin, imidazoles such as clotrimazole or miconazole. Systemic antifungal agents are indicated in case or poor compliance to topical agents, in prophylaxis of highly relapsing disease, in oesophageal candidiasis and in Candida onychomycosis. A topical antifungal agent is the first choice to treat Candida intertrigo. In any case predisposing factors should be eradicated or amended. Infection to Malassezia spp. are treated topically with azoles or selenium sulphur. Oral ketoconazole is an alternative in severe cases. Dermatophytosis requires a systemic antifungal treatment such as terbinafine in chronic, dry, moccassin type palmoplantar infection and for onychomycosis. Intertrigo and tinea corporis are treated with topical agents such as azoles, terbinafine or tolnaftate. Tinea capitis responds to oral griseofulvine, however a topical antifungal must be added to eradicate contagious conidia. Whatever the localisation is, an other superficial site of infection must be looked for and a source of infection should be investigated and eradicated.
J Eur Acad Dermatol Venereol. 2003 Nov;17(6):627-40.
Gupta AK, Adamiak A, Cooper EA.
Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook site) and the University of Toronto, Toronto, Canada.
The efficacy and safety of terbinafine in children.
Terbinafine is an allylamine antifungal agent that has been effective and safe in the treatment of superficial and some deep mycotic infections in adults. An increasing amount of data is available where terbinafine has been used in the paediatric population to treat superficial fungal infections, in particular tinea capitis. The data suggest that terbinafine is effective and safe using treatment regimens that involve short duration therapy, leading to an increased compliance and providing a cost-effective means of treating paediatric superficial fungal infections such as tinea capitis. Terbinafine has been approved for the treatment of tinea capitis in many countries worldwide, and provides good efficacy rates for Trichophyton tinea capitis using shorter regimens than the gold standard griseofulvin. The adverse events profile for children is similar to that in adults with few adverse effects associated with its use. The evidence favours the use of terbinafine in the treatment of superficial infections in children.
J Eur Acad Dermatol Venereol. 2004 Mar;18(2):155-9.
Devliotou-Panagiotidou D, Koussidou-Eremondi TH.
Department of Dermatology, Aristoteles University of Thessaloniki, Mycological Laboratory of the State Hospital for Skin and Venereal Diseases, Chalkidikis 51, GR-54644, Thessaloniki, Greece.
Efficacy and tolerability of 8 weeks' treatment with terbinafine in children with tinea capitis caused by Microsporum canis: a comparison of three doses.
BACKGROUND: Tinea capitis caused by Microsporum canis is the most common mycosis of the scalp in preschool and school-aged children in Greece. OBJECTIVE: To compare the efficacy, safety and tolerability of an 8-week course of oral terbinafine at different doses. METHODS: Patients received oral terbinafine at doses ranging from 3.3 to 12.5 mg/kg/day for 8 weeks, as follows: group A, terbinafine 3.3 to 6.0 to 7.0 mg/kg/day (23 patients); group C, terbinafine > 7.0 to 12.5 mg/kg/day (37 patients). Fungal microscopy and cultures were performed 4 weeks before the start of the treatment, at the end of the treatment (week 8) and at a follow-up visit at week 16. RESULTS: At week 8 mycological cure was achieved in one patient (2.7%) in group A, in 21 patients (91.3%) in group B and in 34 patients (97.1%) in group C. At week 16 mycological cure was achieved in one patient (2.7%) in group A, in 22 patients (95.7%) in group B and in 35 patients (100%) in group C. There was a statistically significant difference (P < 0.0005) between dose level and efficacy of terbinafine at the end of the treatment period and also at the follow-up visit at week 16. Five patients (three in group A and two in group C) discontinued treatment because of adverse events. CONCLUSIONS: The administration of terbinafine at a dose of either 6-7 or 7-12.5 mg/kg/day for 8 weeks is safe and effective for the treatment in children of tinea capitis caused by M. canis.
Ann Hepatol. 2003 Jan-Mar;2(1):47-51.
Zapata Garrido AJ, Romo AC, Padilla FB.
Hospital Christus Muguerza, Monterrey, Nuevo Leon, Mexico.
Terbinafine hepatotoxicity. A case report and review of literature.
We report a 53-year old Mexican female who developed liver dysfunction following a seven-day course of treatment with terbinafine for onychomycosis. She presented with jaundice and abdominal pain. Her serum bilirubin levels showed a peak value of 23.2 mg/dL seven weeks after discontinuing the medication. Infectious causes (hepatitis viruses A, B and C) were excluded. Imaging studies of the abdomen did not reveal any abnormalities. Serum iron and ceruloplasmin levels were normal. Autoantibodies were negative. A liver biopsy revealed necrosis and mononuclear infiltration of the parenchyma, mainly along the sinusoids and surrounding the portal spaces and biliary ducts. Eosinophil infiltration of the portal spaces was also noted. Treatment with ursodeoxycholic acid and ademethionine was started. Her liver tests normalized in the sixth months after stopping terbinafine.
Int J Cancer. 2004 Aug 10;111(1):51-9.
Ho PY, Liang YC, Ho YS, Chen CT, Lee WS.
Graduate Institute of Cellular and Molecular Biology, Taipei Medical University, Taipei, Taiwan.
Inhibition of human vascular endothelial cells proliferation by terbinafine.
We have demonstrated previously that terbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, suppresses proliferation of various cultured human cancer cells in vitro and in vivo by inhibiting DNA synthesis and activating apoptosis. In our study, we further demonstrated that TB at a range of concentrations (0-120 microM) dose-dependently decreased cell number in cultured human umbilical vascular endothelial cells (HUVEC). Terbinafine was not cytotoxic at a concentration of 120 microM, indicating that it may have an inhibitory effect on the cell proliferation in HUVEC. The TB-induced inhibition of cell growth rate is reversible. [(3)H]thymidine incorporation revealed that TB reduced the [(3)H]thymidine incorporation into HUVEC during the S-phase of the cell-cycle. Western blot analysis demonstrated that the protein levels of cyclin A, but not cyclins B, D1, D3, E, CDK2 and CDK4, decreased after TB treatment. The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Pretreatment of HUVEC with a p21 specific antisense oligonucleotide reversed the TB-induced inhibition of [(3)H]thymidine incorporation. Taken together, these results suggest an involvement of the p21-associated signaling pathway in the TB-induced antiproliferation in HUVEC. Capillary-like tube formation and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of TB. These findings demonstrate for the first time that TB can inhibit the angiogenesis.
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