INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo DERMAX 250 (tablets)

SCHEDULING STATUS
S4

PROPRIETARY NAME
(and dosage form):

DERMAX 250 (tablets)

COMPOSITION
DERMAX 250 : Each tablet contains 250 mg
terbinafine as terbinafine hydrochloride

PHARMACOLOGICAL CLASSIFICATION
A20.2.2 Antimicrobial (Chemotherapeutic) agents. Fungicides.

PHARMACOLOGICAL ACTION
Pharmacodynamics
Terbinafine is an allylamine which has a broad spectrum of antifungal activity. At low concentrations terbinafine is fungicidal against dermatophytes, moulds and certain fungi. The activity is fungicidal or fungistatic depending on the species.
Terbinafine interferes specifically with fungal sterol biosynthesis at an early stage. This leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine acts by inhibition of squalene epoxidase in the fungal cell membrane.
The enzyme squalene epoxidase is not linked to the cytochrome P-450 system.
When given orally, the medicine concentrates in skin at levels associated with fungicidal activity.
Pharmacodynamics:
A single oral dose of 250 mg of terbinafine results in mean peak plasma concentrations of 0,87 micrograms/mL within 2 hours after administration. The absorption half-life is 0,6 hours and the distribution half-life is 4,6 hours. Terbinafine binds strongly to plasma proteins. It rapidly difuses through the dermis and concentrates in the lipophyllic stratum corneum.
Terbinafine is also secreted in sebum, thus achieving high concentrations in hair follicles, hair and sebum rich skins. There is also evidence that terbinafine is distributed into the nail plate within the first few weeks of commencing therapy. Biotransformation results in metabolites with no antifungal activity, which are excreted predominantly in the urine. The elimination half-life is 17 hours. There is no evidence of accumulation.
No age-dependent changes in pharmacokinetics have been observed but the elimination rate may be reduced in patients with renal or hepatic impairment, resulting in higher blood levels of terbinafine.
The bioavailability of terbinafine is unaffected by food.

INDICATIONS
DERMAX is indicated in the treatment of:
Fungal infections of the skin caused by Trichophyton (e.g. T. rubrum, T menagrophytes, T. verrucosum, T. violaceum). Micosporum canis, Epidermophyton floccosum
ringworm (tinea corporis, tinea cruris andtinea pedis) where oral therapy is considered appropriate due to the site, severity or extent of the infection
yeast infection of the skin caused by candida (e.g. Candida albicans)
onychomycosis

CONTRA-INDICATIONS
Hypersensitivity to terbinafine hydrochloride or any of the excipients
Impaired liver function
Safety in pregnancy and lactation has not been demonstrated

WARNINGS
None known.

INTERACTIONS
The plasma clearance of DERMAX may be accelerated by medicines which induce metabolism (such as rifampicin) and may be inhibited by drugs which inhibit cytochrome P-450 (such as cimetidine). Where co-administration of such agents is necessary the dosge of DERMAX may need to be adjustad accordingly.
It has been reported that DERMAX inhibits the CYP2D6- mediated metabolism. This in vitro finding may be of clinical relevance for patients receiving compounds predominantly metabolized by this enzyme, such as tricyclic antidepressants (TCA’s), beta-blockers, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAO-Is) Type B.
Other studies undertaken in vitro and in healthy volunteers suggest that DERMAX shows negligible potential to inhibit or induce the clearance of drugs that are metabolized via other cytochrome P-450 enzymes (e.g. cyclosporin, tolbutamine, terfenadine, triazolam, oral contraceptives). However, some cases of menstrual disturbance (breakthrough bleeding and irregular cycle) have been reported in patients taking DERMAX concomitantly with oral contraceptives.

PREGNANCY AND LACTATION
There is no clinical experience with DERMAX in pregnant women. Terbinafine is excreted in breast milk and therefore mothers should not receive treatment with DERMAX while breast-feeding.

DOSAGE AND DIRECTIONS FOR USE:
The duration of treatment varies according to the indication and the severity of the infection, 250 mg once daily.

Skin infections:
Likely durations of treatment are as follows:
Tinea pedis (interdigital, plantar/moccasin type):         2 to 6 weeks
Tinea corporis:         2 to 4 weeks
Tinea cruris:         2 to 4 weeks
Cutaneous candidiasis:         2 to 4 weeks
Onychomycosis: The duration of treatment for most patients is between 6 weeks and 3 months. Treatment periods of less than 3 months can be anticipated in patients with fingernail infection, toenail infection other than the big toe, or patients of younger age. In the treatment of toenail infections, 3 months is usually sufficient although a few patients may require treatment of 6 months or longer. Poor nail outgrowth during the first weeks of treatment may enable identification of those patients in whom longer therapy is required.
Complete resolution of the signs and symptoms of infection may not occur until several weeks after mycological cure.
Children
As data is still limited its use is not recommended.
Elderly
There is no evidence to suggest that elderly patients require different dosages or experience side-effects different from those of younger patients. The possibility of impairment of liver or kidney function should be considered in this age group.
Impaired renal function
Patients with impaired renal function (creatinine clearance less than 50 mL/minute or serum creatinine of more than 300 micromol/L should receive half the normal dose.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects
Gastrointestinal Disorders:
Frequent: Dyspepsia, fullness, loss of appetite, nausea, mild abdominal pain, diarrhoea.
Taste loss and taste disturbance have been reported in approximately 0,6% of patients treated with DERMAX. This usually resolves slowly on discontinuation of medicine.
Nervous System Disorders:
Less frequent: Psychiatric disturbances such as depression and anxiety, headache.
Paraesthesia, hypoaesthesia, dizzines, vertigo, malaise and fatigue.
Skin and Subcutaneous Disorders:
Less frequent: Stevens-Johnson syndrome, toxic epidermal necrolysis, rash, urticaria, photosensitivity and angioneurotic oedema, psoriasis. If progressive skin rash occurs, treatment with DREMAX should be discontinued.
Hepato-biliary Disorders:
Frequent: Jaundice, cholestasis and hepatitis. If hepatic dysfunction develops, treatment with DERMAX should be discontinued (see PRECAUTIONS FOR USE).
Haematological Disorders:
Less frequent: Neutropenia, thrombocytopenia and agranulocytosis.
Other side-effects reported include:
Musculoskeletal disorders including arthralgia and myalgia. These may occur as part of a hypersensitivity reaction in association with allergic skin reactions.

Special Precautions:
Rarely, cases of cholestasis and hepatitis have been reported. These usually occur within two months of starting treatment.
If a patient presents with signs or symptoms suggestive of liver dysfunction such as pruritus, unexplained persistent nausea, anorexia or tiredness, or jaundice, vomiting, fatigue, abdominal pain or dark urine, or pale stools, hepatic origin should be verified and DERMAX should be discontinued.
Single dose pharmacokinetic studies in patients with pre-existing liver disease have shown that the clearance of DERMAX may be reduced by about 50%. The therapeutic use of DERMAX in patients with chronic or active liver disease has not been studied in prospective clinical trials, and therefore csannot be recommended.
DERMAX should be used with caution in patients with psoriasis as very rare cases of exacerbation of psoriasis have been reported.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
A few cases of overdose (up to 5 g) have been reported, giving rise to hedache, nausea, epigastric pain and dizziness. The recommended treatment of overdosage consists of eliminating the drug, primarily by the administration of activated charcoal, and giving symptomatic supportive therapy if needed.

IDENTIFICATION:
DERMAX 250: White, round, flat, beveled edged tablets embossed “R250”on one side and a bisecting line on the other side.

PRESENTATION:
Aluminium foil/PVC/PVDC blisters in cartons of 14 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C in the original container protected from moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
DERMAX 250: 40/20.2.2/0344

NAME AND BUSINESS ADDRESS OF APPLICANT:
Dr. Reddy's Laboratories (Pty) Ltd
3rd Floor, TA Bank Building,
160 Jan Smuts Avenue
Rosebank
2196 Johannesburg

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
August 2006

New addition to this site: February 2007
Source: Pharmaceutical Industry


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