What is Terbasil?
Terbasil is an allylamine medicine used to treat fungal infections. It is especially effective against dermatophytes (tinea infections).
The original brand is Lamisil®. In New Zealand (2016) it is available as 250 mg tablets (Dr Reddy's Terbasil, fully funded by PHARMAC) and Terbasil-DRLA. The tablets require a doctor's prescription. Topical options include creams, gel , solution and spray from various manufacturers, and are available at a pharmacy without a prescription.
How does Terbasil control fungal infections?
Terbasil inhibits a fungal enzyme , squalene epoxidase, and stops the cells making ergosterol, the main component of the cell wall.
Animal Toxicology and/or Pharmacology
A w >in vivo studies in mice, rats, dogs, and monkeys, and in vitro studies using rat, monkey, and human hepatocytes suggest that peroxisome proliferation in the liver is a rat-specific finding. However, other effects, including increased liver weights and APTT, occurred in dogs and monkeys at doses giving C ss trough levels of the parent Terbasil 2 to 3 times those seen in humans at the MRHD. In a 52-week oral toxicology study conducted in juvenile maturing dogs, increased heart and liver weights were noted in males and signs of CNS disturbance including 3 cases of single episodes of seizures were noted in females at the highest dose tested, 100 mg/kg/day . No treatment related findings were noted at 30 mg/kg/day in this study.
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because treatment of onychomycosis can be postponed until after pregnancy is completed, it is recommended that Lamisil Tablets not be initiated during pregnancy.
Oral reproduction studies have been performed in rabbits and rats at doses up to 300 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to Terbasil.
Terbasil is a member of the allylamine group of antifungals. It inhibits ergosterol biosynthesis by inhibiting squalene epoxidase, a catalyst of the conversion of squalene to squalene epoxide. This resulting accumulation of squalene within the fungal cell and depletion of ergosterol in the fungal cell membrane causes cell death . Terbasil is highly selective for fungal squalene epoxidase and has no effect on human sterol synthesis . It has in vitro activity against a wide range of organisms, including dermatophytes, several melanized molds, Aspergillus, Cryptococcus, and several dimorphic fungi, although it is mainly used to treat dermatophytosis . It is available as oral and topical preparations.
Terbasil has good oral bioavailability (70–80%), and absorption is not affected by food. All allylamines are highly lipophilic and hence Terbasil achieves high concentrations in the stratum corneum, sebum, and nail. It is extensively metabolized in the liver, and 15 metabolites have been identified which are subsequently excreted in urine (80%) and feces (20%) . At least 7 CYP enzymes are involved in Terbasil metabolism, of which 1A2, 2C9, and 3A4 are the most important . Elimination takes place slowly, with an initial half-life of 22 hours and another at 90 hours, probably reflecting slow release from adipose tissue . Use of Terbasil is not recommended in patients with active or chronic liver disease or with creatinine clearance .
Initially, it was thought that Terbasil did not have any inhibitory effect on the CYP enzymes , but it is now known to be a potent competitive inhibitor of CYP2D6, although it has been suggested that one of its metabolites, rather than the parent drug, causes this . Because CYP2D6 constitutes only 1.5% of the total liver CYP, there are minimal interactions via this route, except with venlafaxine and amitriptyline . Cimet >
An evaluation of the effect of food on Terbasil tablets was conducted. An increase of less than 20% of the AUC of Terbasil was observed when Terbasil tablets were administered with food. Terbasil tablets can be taken with or without food.
This medication contains Terbasil. Do not take Lamisil if you are allergic to Terbasil or any ingredients contained in this drug.
Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.
Terbasil is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, Cr. neoformans and some but not all Candida and Aspergillus spp. 177 Cross-resistance in Candida spp. following treatment with fluconazole can occur due to upregulation of target enzymes. Multidrug efflux pumps may also reduce susceptibility. 178
Terbasil is indicated for cutaneous dermatophytoses and onychomycoses that warrant systemic therapy. Recommended durations of treatment for tinea capitis, tinea corporis, tinea pedis and onychomycosis in adults are 4, 2, 6, and 12 weeks, respectively. Terbasil cannot be recommended for the treatment of deeply invasive mycoses.
Pharmacology and toxicology
Terbasil is used for both oral and topical therapy of nail mycoses and various tineal skin infections. There is little experience with its use during human pregnancy. In an ongoing study, the Canadian Motherisk program reports on 54 pregnancies exposed to Terbasil; of these, 24 were exposed to systemic therapy and 23 to topical; 24 were exposed during the first trimester. Data collected thus far appear to suggest no increased risk for major malformations ( Sarkar 2003 ).
Terbasil should not be used during pregnancy, because data on pregnancy outcome are lacking and nail mycosis is not a condition requiring urgent treatment. Inadvertent pregnancy exposure does not require termination of pregnancy. Detailed fetal ultrasonography can be considered after first-trimester exposure.
Terbasil has been most extensively studied for the treatment of dermatophytes. There are few clinical studies of Terbasil use in veterinary patients with other fungal infections. In the cat the drug shows great promise in the treatment of dermatophytes. In humans the drug is most extensively used in the treatment of onychomycosis, dermatophytosis and tinea infections. Pharmacoeconomically, it is considered the drug of choice for treating dermatophyte infections in humans. It also has shown good efficacy when used to treat sporotrichosis. Systemic mycoses are typically less responsive than the superficial mycoses.
Terbasil is sometimes combined with itraconazole for the treatment of mycotic infections that are traditionally difficult to treat medically, such as pheohyphomycosis, hyalohyphomycosis, systemic aspergillosis, pythiosis and lagenidiosis.
What Other Drugs Interact with Terbasil?
If your doctor has directed you to use this medication for your condition, your doctor or pharmacist may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider or pharmacist first.
Terbasil has no known severe or serious interactions with other drugs.
Moderate Interactions of Terbasil include:
Mild Interactions of Terbasil include:
This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.
Patient Counseling Information
Advise the patient to read the FDA-Approved Medication Guide.
Patients taking Terbasil tablets should receive the following information and instructions:
- Advise patients to immediately report to their physician or get emergency help if they experience any of the following symptoms: hives, mouth sores, blistering and peeling of skin, swelling of face, lips, tongue, or throat, difficulty swallowing or breathing. Terbasil tablets treatment should be discontinued.
- Advise patients to immediately report to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. Terbasil tablets treatment should be discontinued.
- Advise patients to report to their physician any signs of taste disturbance, smell disturbance and/or depressive symptoms, fever, skin eruption, lymph node enlargement, erythema, scaling, loss of pigment, and unusual photosensitivity that can result in a rash. Terbasil tablets treatment should be discontinued.
- Advise patients to minimize exposure to natural and artificial sunlight (tanning beds or UVA/B treatment) while using Terbasil tablets.
- Advise patients that if they forget to take Terbasil tablets, to take their tablets as soon as they remember, unless it is less than 4 hours before the next dose is due.
- Advise patients to call their physician if they take too many Terbasil tablets.
- Advise patients to call their physician if they become pregnant during treatment with Terbasil tablets.
Medication Gu >www.northstarrxllc.com/products or call 1-800-206-7821. Manufactured for: Northstar Rx LLC Memphis, TN 38141.
Manufactured by: Aurobindo Pharma Limited Hyderabad-500 090, India.