Terbinafine (Lamisil) is an antifungal medicine that is available both as oral tablets and topical formulations for the treatment of fungal infections.

• Onychomycosis (tablets only):

  • It is used in the treatment of onychomycosis of the toenail or fingernail caused by dermatophytes (tinea unguium).

• Tinea capitis (granules only):

  • It is used in the treatment of tinea capitis in patients 4 years and older.

• Off Label Usage of Terbinafine in Adults:

• It is also used in following conditions:

  • Dermatophyte folliculitis (tinea barbae, Majocchi granuloma);

  • Sporotrichosis (lymphocutaneous and cutaneous);

  • Tinea capitis;

  • Tinea corporis/tinea cruris/tinea faciei;

  • Tinea pedis/tinea manuum

Terbinafine Dose in Adults

Terbinafine dosage in the treatment of Onychomycosis:

• Continuous dosing:

  • 250 mg tablets orally once daily given for 6 weeks (fingernail) or 12 weeks (toenail).

• Pulsed dosing (alternative dosing method) (off-label):

  • 250 mg tablets orally once daily given for 4 weeks, then off for 4 weeks, then resume with 250 mg once daily for 4 weeks or 250 mg twice daily for 7 days repeated every 4 weeks for 3 months
  • Pulsed dosing is less useful but may reduce the risk of adverse effects, reduce cost, and improve patient compliance

Dosage in the treatment of Sporotrichosis, lymphocutaneous and cutaneous (alternative agent for patients who do not respond to itraconazole) (off-label):

• 500 mg tablets orally twice daily given
• Treat for 2 to 4 additional weeks after all lesions have been resolved
• The usual duration is 3 to 6 months

Dosage in the treatment of Tinea infections:

• Dermatophyte folliculitis (tinea barbae, Majocchi granuloma) (off-label):

  • 250 mg tablets orally once daily given
  • duration is typically 2 to 6 weeks but might need to be extended (eg, in immunocompromised patients with slow response)

• Tinea capitis (off-label):

  • 250 mg tablets orally once daily given for 4 to 6 weeks.

• Tinea corporis/tinea cruris/tinea faciei (alternative agent) (off-label):

  • Lamisil may be used as an alternative treatment for patients in whom topical therapy has failed and those with extensive skin involvement.
  • 250 mg tablets orally once daily given for 1 to 2 weeks

Tinea pedis/tinea manuum (alternative agent) (off-label):

• Lamisil may be used as an alternative treatment for patients in whom topical therapy has failed and those with extensive skin involvement.
• 250 mg tablets orally once daily given for 2 weeks

Terbinafine dose in Childrens

Dosage in the treatment of Tinea capitis:

• Children ≥4 years and Adolescents: Oral: Granules:
  • <25 kg:
    • 125 mg once daily given for 6 weeks
  • 25 to 35 kg:
    • 5 mg once daily given for 6 weeks
  • >35 kg:
    • 250 mg once daily given for 6 weeks

Terbinafine dosage in the treatment of Onychomycosis:

• Children and Adolescents:
  • 10 to 20 kg:
    • 5 mg orally once daily given for 6 weeks (fingernails) or 12 weeks (toenails)
  • 20 to 40 kg:
    • 125 mg orally once daily given for 6 weeks (fingernails) or 12 weeks (toenails)
  • >40 kg:
    • 250 mg orally once daily given for 6 weeks (fingernails) or 12 weeks (toenails)

Terbinafine pregnancy Risk category: B

• There is insufficient published information on the use of systemic Terbinafine during pregnancy.
• Pregnancy is not a good time to try systemic therapy for tinea capitis or onychomycosis.

Terbinafine use during breastfeeding:

• Breast milk usually contains Terbinafine.
• It is not recommended to breastfeed during systemic treatment
• According to the manufacturer breastfeeding during therapy should be considered in light of the risks to infants and the benefits to mothers.

Terbinafine (Lamisil) dose in renal disease:

• There are no dosage adjustments given in the manufacturer's labeling (has not been studied)
• But, clearance is decreased by 50% in patients with CrCl ≤50 mL/minute.

Terbinafine Dose in Liver Disease:

• It is Contraindicated in chronic or active hepatic disease.

Common Side Effects of Terbinafine Include:

• Central nervous system:

  • Headache

Less Common Side Effects of Terbinafine Include:

• Dermatologic:

  • Skin Rash
  • Pruritus
  • Urticaria

• Gastrointestinal:

  • Diarrhea
  • Vomiting
  • Dyspepsia
  • Upper Abdominal Pain
  • Dysgeusia
  • Nausea
  • Abdominal Pain
  • Pharyngolaryngeal Pain
  • Toothache

• Hepatic:

  • Liver Enzyme Disorder

• Infection:

  • Influenza

• Ophthalmic:

  • Vision Color Changes
  • Decreased Visual Acuity

• Respiratory:

  • Nasopharyngitis
  • Cough
  • Upper Respiratory Tract Infection
  • Nasal Congestion
  • Rhinorrhea

• Miscellaneous:

  • Fever

Contraindication to Terbinafine Include:

• Hypersensitivity to terbinafine and any component of the formulation
• Chronic or active hepatic diseases

Warnings and precautions

• Antifungal hypersensitivity to Allylamine

  • Patients sensitive to allylamine antifungals (eg naftifine or butenafine), should be cautious.
  • Cross-sensitivity to Terbinafine could exist.

• Depression

  • It was seen with the use
  • Patients should report any depressive symptoms or mood changes.

• Gastrointestinal effects:

  • There have been cases of severe cases where taste disturbances (including loss or impairment) can lead to decreased food intake, weight loss, anxiety, and depression.
  • Sometimes, the resolution may take several weeks or more to occur after therapy has ended. In some cases, the disturbance could be permanent.
  • Stop treating patients suffering from taste disturbances.

• Hematologic effects

  • Clinical trials showed that absolute lymphocyte count decreased in a temporary manner.
  • Also, severe neutropenia has been reported (reversible after discontinuation).
  • If treatment is to be administered for more than 6 weeks, monitor the CBC.
  • If ANC is less than 1,000/mm, stop therapy

• Hepatic failure

  • There have been cases of hepatic dysfunction that can lead to liver transplantation or even death.
  • This could occur in both patients with and without a preexisting liver disease.
  • Patients with chronic or active hepatic disease may experience more severe hepatic events.
  • At baseline, liver function tests should always be done.
  • If there is any evidence of liver injury (eg, nausea or vomiting, right upper abdominal pain, jaundice and dark urine, pale stool) or elevated liver function test results, discontinue use.

• Hypersensitivity

  • Severe skin and hypersensitivity reactions have been reported (eg, Stevens Johnson syndrome, toxic epidermal Necrolysis, bullous Dermatitis, Stevens-Johnson Syndrome, bullous Dermatitis, toxic epidermal Neolysis, bullous Dermatitis, exfoliative Dermatis Drug Reaction with Eosinophilia, and Systemic Symptoms [DRESS] syndrome).
  • Stop treating if you experience progressive skin rash, or hypersensitivity reactions.

• Ocular effects

  • Even though it is rare, there have been changes in the retina and ocular lenses.
  • It is possible to discontinue therapy.

• Respiratory effects

  • There have been reports of smell disturbances (including loss or smell).
  • Sometimes, the resolution may take longer than expected, such as >1 year after discontinuation of therapy. In some cases, it may become permanent.
  • Stop treating patients suffering from smell disturbance.

• Thrombotic microangiopathy

  • There have been cases of thrombotic miopathy (TMA), which includes hemolytic uremic syndrome and thrombotic tubular purpura.
  • Stop if TMA occurs
  • Consider the possibility of TMA due to unexplained anemia and thrombocytopenia.

• Autoimmune disease (Lupus).

  • It has been observed that cutaneous and systemic lupus are susceptible to precipitation or exacerbation.
  • If you notice any signs or symptoms, stop immediately.

• Hepatic impairment

  • Patients with chronic or active hepatic disease are not advised to use this medication.
  • Clearance is almost half-dead in hepatic cystsis.

• Renal impairment

  • Patients with kidney dysfunction (CrCl =50mL/minute) should be cautious. Clearance is reduced by nearly 50%

Terbinafine (systemic): Drug Interaction

Monitor:

• Liver function tests at baseline and periodically during treatment
• CBC (if used >6 weeks; immunosuppressed patients only)
• taste and/or smell disturbances

How to administer Terbinafine (lamisil)?

• Give tablets without regard to meals.
• Give granules with food; sprinkle granules on a spoonful of pudding or other soft, nonacidic food (eg, mashed potatoes)
• swallow entire spoonful without chewing
• The granules should not be mixed with applesauce or other fruit-based foods.

Mechanism of action of Terbinafine (Lamisil):

• It is a synthetically manufactured allylamine derivative which inhibits squalene-epoxidase. This enzyme is crucial in sterol biosynthesis in yeasts.
• This causes fungal cell death and a defect in the ergosterol in the fungal cell membrane.

Absorption:

• Children and Adults: >70%

Distribution:

• Distributed to sebum and skin predominantly

Protein binding:

• Plasma: >99%

Metabolism:

• Hepatic predominantly via CYP1A2, 3A4, 2C8, 2C9, and 2C19 to inactive metabolites

Bioavailability:

• Children 36% to 64%
• Adults: 40%

Half-life elimination:

• Terminal half-life: 200 to 400 hours
• It has a very slow release of drug from the skin and adipose tissues occur
• The effective half-life in children is 27 to 31 hours and in adults is about 36 hours

Time to peak, plasma:

• Children and Adults: Within 2 hours

Excretion:

• Via Urine (80%, primarily as inactive metabolites) & feces (20%)

International Brands of Terbinafine:

• ACT Terbinafine
• APO-Terbinafine
• Auro-Terbinafine
• DOM-Terbinafine
• JAMP-Terbinafine
• LamISIL
• MYLAN-Terbinafine
• PHL-Terbinafine
• PMS-Terbinafine
• RIVA-Terbinafine
• SANDOZ Terbinafine
• Terbinafine-250
• TEVA-Terbinafine
• Amizil
• Antifin
• Atifan
• Camisan
• Cutis
• Deolate
• Derfin
• Dermafin
• Dermasil
• Dermatin
• Dermax
• Dicil
• EU2000
• Finex
• Fungasil
• Funginix
• Fungitech
• Fungizid
• Fungotek
• Fungster
• Funzal
• Interbi
• L:isim
• Lamifen
• Lamisil
• Lamisil AT
• Lamisil Dermgel
• Lamisil Once
• Lamisilate
• Lammifen
• Lapiderm
• Micoset
• Micozone
• Muzona
• Mycelvan
• Nailderm
• Patir
• Periafin
• Ronasil Derm Gel
• Sebifin
• Skinabin
• SolvEasy Tinea Cream
• Tamsil
• Tenabin
• Terbex
• Terbicip
• Terbifin
• Terbihexal
• Terbin
• Terbix
• Terekol
• Terfex
• Terfine
• Terfung
• Tiersil Once
• Zabel

Terbinafine brands in Pakistan: