What Is Terbinafine?
This product is an allylamine antifungal drug, which inhibits squalene epoxidase during the synthesis of ergosterol in fungal cells, and causes squalene to accumulate in cells to play a bactericidal role. The sensitivity of human cells to this product is one ten thousandth of that of fungi. This product has a broad-spectrum antifungal effect, bactericidal effect on skin fungi, and antibacterial effect on Candida albicans. It is suitable for skin and nail infections caused by superficial fungi, such as Trichophyton, Microsporum canis, Epidermophyton floccus, and other infections such as ringworm, jock itch, athlete's foot, onychomycosis, and candida albicans.
- Drug Name
- Terbinafine
- Alias
- Lelexu, Therapycin, etc.
- Foreign name
- Terbinafine
- Drug type
- Allylamines
- Molecular formula
- C21H25N
- Molecular weight
- 291.43000
- CAS
- 91161-71-6
- This product is an allylamine antifungal drug, which inhibits squalene epoxidase during the synthesis of ergosterol in fungal cells, and causes squalene to accumulate in cells to play a bactericidal role. The sensitivity of human cells to this product is one ten thousandth of that of fungi. This product has a broad-spectrum antifungal effect, bactericidal effect on skin fungi, and antibacterial effect on Candida albicans. It is suitable for skin and nail infections caused by superficial fungi, such as Trichophyton, Microsporum canis, Epidermophyton floccus, and other infections such as ringworm, jock itch, athlete's foot, onychomycosis, and candida albicans.
Terbinafine compound introduction
- Terbinafine hydrochloride, trade name Lamisil, is an acrylamine antifungal drug artificially produced by Novartis (a Swiss pharmaceutical company). It is highly hydrophobic and therefore tends to accumulate in hair, skin, nails and adipose tissue. Terbinafine is listed on the World Health Organization's Standard List of Essential Medicines and is one of the essential medicines in the basic medical system.
Terbinafine Basic Information
- Chinese name: terbinafine
- Chinese alias: (E) -N- (6,6-dimethyl-2-hepten-4-ynyl) -N-methyl-1-naphthylmethylamine; terbinafine base; terbinafine ;
- English name: Terbinafine
- English alias: SF-86-327; Lamasil; (E) -N, 6,6-trimethyl-N- (naphthalen-1-ylmethyl) hept-2-en-4-yn-1-amine; Lamisil Tablet; Lamisil ;
- CAS number: 91161-71-6
- Molecular formula: C 21 H 25 N
- Molecular weight: 291.43000
- Exact mass: 291.19900
- PSA: 3.24000
- LogP: 4.87730
Terbinafine physical and chemical properties
- Appearance and properties: white to off-white crystalline powder
- Density: 1.007g / cm 3
- Boiling point: 417.9ºC at 760 mmHg
- Flash point: 183.7ºC [1]
Terbinafine molecular structure data
- 1. Molar refractive index: 97.09
- 2. Molar volume (cm / mol): 289.1
- 3. Isotonic specific volume (90.2K): 731.9
- 4. Surface tension (dyne / cm): 41.0
- 5. Polarizability (10-24cm3): 38.48
Terbinafine calculated chemical data
- 1. Hydrophobic parameter calculation reference value (XlogP): 5.6
- 2.Number of hydrogen bond donors: 0
- 3.Number of hydrogen bond acceptors: 1
- 4.Number of rotatable chemical bonds: 5
- 5.Number of tautomers: none
- 6. Topological molecular polar surface area 3.2
- 7.Number of heavy atoms: 22
- 8.Surface charge: 0
- 9.Complexity: 428
- 10.Number of isotope atoms: 0
- 11. Determine the number of atomic stereocenters: 0
- 12. Uncertain number of atomic stereocenters: 0
- 13. Determine the number of chemical bond stereocenters: 1
- 14. Uncertain number of chemical bond stereocenters: 0
- 15.Number of covalent bond units: 1
Terbinafine synthesis method
- Condensation is carried out using chloro-t-butane and ethyl chloride as raw materials in the presence of aluminum trichloride. Then in the presence of potassium hydroxide, it is heated at a high temperature in dimethyl sulfoxide to eliminate two molecules of hydrogen chloride. The obtained material is reacted with ethyl magnesium bromide at room temperature, and then reacted with acrolein to form 6,6-dimethyl-1-heptene-4-yn-3-ol. Finally bromination gives cis-trans-1-bromo-6,6-dimethyl-2-heptene-4-yne. The obtained product and N-methyl-1-naphthylmethylamine are condensed under the action of sodium carbonate to obtain terbinafine and its cis isomer. The two can be separated by recrystallization from isopropanol, or by column chromatography. [2]
Terbinafine related drug label information
Terbinafine classification name
- Primary classification: Dermatological medication Secondary classification: Antifungal drugs
Terbinafine Drug English Name
- Terbinafine
Terbinafine drug alias
- Lamex, Dink, Mycoxil, Mythromycin, Trinaphthofen, Lamex, Lamisil
Terbinafine drug dosage form
- 1. Tablet: 125mg, 250mg; 2. Capsule: 250mg; 3. Cream: 1%; 4. Cream: 1g (0.01g), 10g (0.1g); 5. Terbinafine hydrochloride cream: 5g (0.05g); 6. Gel: 10g (0.1g); 7. Solution: 0.1g (10ml).
Terbinafine pharmacological effects
- Terbinafine is an acrylamine antifungal drug that inhibits fungal squalene epoxidase. This enzyme is one of the key enzymes in the synthesis of ergosterol in the fungal cell membrane, so this drug can interfere with ergosterol. Biosynthesis, the excessive accumulation of squalene in the fungal cells and the synthesis of ergosterol are hindered, thereby playing a bactericidal or bacteriostatic role. Terbinafine does not affect the cytochrome P450 enzyme system, so it does not affect human hormones and related drug metabolism. Terbinafine is lipophilic and keratotropic, so the concentration in the skin, hair, and deck is higher, and the effective antibacterial concentration in the cuticle of the skin can be maintained for 1 month after the drug is stopped, and the effective concentration in the deck is about 2 to 3 months. The drug is more active against dermatophytes and aspergillus than naftifine, ketoconazole, itraconazole, clotrimazole, econazole, griseofulvin and amphotericin. This medicine has broad-spectrum antifungal activity, and especially has strong bactericidal or bacteriostatic effects on dermatophyte (Trichophyton rubrum, Trichophyton rubrum, etc.). It has bactericidal effects on filamentous bodies, dark fungi, yeasts, aspergillus, dermatitis, and capsular cytoplasmic bacteria. It also has a strong antibacterial effect on S. spores, Candida albicans, Candida subtilis and P. ovale.
Terbinafine pharmacokinetics
- The drug is rapidly absorbed orally. After 2 hours of oral administration, the peak blood concentration is 0.97 g / ml, and the steady-state concentration is reached within 10 to 14 days. The plasma protein binding rate is as high as 99%. This drug has an absorption half-life of 1 h and a distribution half-life of 4.6 h. This drug is metabolized in the liver, 70% is excreted from urine, and partly excreted from feces. The excretion amount in urine within 72h reaches 85%, so this medicine has no accumulation effect. The milk excretion rate of this medicine is less than 0.2%. Hepatic and renal dysfunction, the clearance rate can be reduced. The elimination half-life of this drug is 17h. For topical terbinafine cream, its absorption rate does not exceed 5%. This product is preferentially distributed to the skin, hair, sebum, sweat, etc., it easily diffuses into the stratum corneum, secretes into milk, is metabolized into inactive metabolites in the liver, and is excreted with the urine. The half-life is 17 hours, severe liver and kidney diseases Patient half-life can change.
Terbinafine indication
- The external preparation of this medicine is suitable for treating various superficial fungal infections, such as tinea pedis, tinea corporis, jock itch, and tinea capitis. Oral preparations can be used for deep mycosis such as onychomycosis and sporotrichosis. For the treatment of onychomycosis (onychomycosis) and fungal infections of the skin and mucous membranes.
Terbinafine Contraindications
- 1. People who are allergic to this medicine or similar drugs. 2. Severe liver and kidney dysfunction.
Terbinafine notes
- 1. Use with caution: (1) those with liver and kidney dysfunction; (2) pregnant women; (3) women with oral contraceptives. 2. Effects of drugs on children: Not recommended for children under 2 years of age. 3. The effect of the drug on breastfeeding: This drug can be excreted through breast milk and should not be breast-fed during oral treatment. Patients taking this medicine for more than 4 to 6 weeks should undergo liver enzyme tests. The dose of cimetidine or rifampin should be reduced when taken orally.
Terbinafine adverse reactions
- This drug is well tolerated. 1. Few have nausea, stomach upset, bloating, lack of appetite, abdominal pain, diarrhea and other gastrointestinal reactions after taking the medicine. 2. Occasionally increased transferases or decreased granulocytes can generally recover after drug withdrawal. 3. Rare taste changes. 4. Topical application may cause local mild burning sensation, itching and other irritation symptoms or local skin dryness, sometimes accompanied by joint pain and myalgia.
Terbinafine usage and dosage
- 1. Adult oral administration: mainly used for the treatment of onychomycosis, tinea capitis and stubborn skin fungal disease. Onychomycosis: 250 mg daily for 4 to 6 weeks (4 weeks for nails and 6 weeks for toenails). Tinea capitis: 250 mg daily for 4 weeks. Keratinized tinea pedis, 250 mg daily for 4 weeks. It can also be used for the treatment of sporotrichosis and aspergillosis, 250mg each time, twice a day for 8 to 10 weeks; (2) external use: topical creams, gels, solutions, etc. are applied to the affected area. Treatment of body and jock itch, 2 times a day for 1 to 2 weeks. Tinea pedis, tinea versicolor, twice daily for 2 to 4 weeks; (3) Dose for renal insufficiency: When the creatinine clearance is less than 50 ml per minute, or the serum creatinine is greater than 300 mol / L, the dose of this medicine should be reduced by 50 %. 2. Oral administration in children: Not recommended for children under 2 years of age. For children over 2 years of age and weighing less than 20kg, 62.5mg each time, once a day, the course of treatment is the same as for adults; for children weighing 20 to 40kg, 125mg each time, once a day, the course of treatment is the same as for adults; body weight greater than 40kg, 250mg each time, 1 day Second, the course of treatment is the same as that of adults. To treat skin and mucous fungal infections, take 250mg orally once daily for 1 to 6 weeks; topical application of 1% cream 1 to 2 times daily for 1 to 2 weeks; for onychomycosis: 250mg orally once daily 1 For 6 to 12 weeks.
Terbinafine drug interactions
- 1. This medicine has a certain synergistic effect with the combination of azole antifungal drugs and amphotericin B. 2. This medicine combined with caffeine can extend the half-life of caffeine. 3. Liver drug enzyme-inducing drugs (such as phenobarbital, rifampicin, etc.) can accelerate the plasma clearance of this drug. Accelerate the metabolism of this medicine. 4. Liver drug enzyme inhibitors (such as cimetidine, etc.) can inhibit the plasma clearance of this drug and inhibit its metabolism. 5. This medicine should not be combined with oral contraceptives. Because very few people may have irregular menstruation.
Terbinafine Drug Evaluation
- This product is acrylamine antibacterial drug with broad-spectrum antifungal activity. It is mainly used for the treatment of ringworm, jock itch, athlete's foot, skin candidiasis, and tinea versicolor. Domestic reports use miconazole as a control, randomized control of 1% terbinafine powder for superficial mycosis, and patients randomly receive terbinafine powder or miconazole powder 2 times a day for 2 weeks for body and jock itch. Tinea tinea and tinea pedis are treated for 3 weeks. After the end of treatment, the clinical efficacy and mycological efficacy were comprehensively evaluated according to clinical symptoms and signs, fungal microscopy and / or culture. The results showed that terbinafine had a cure rate of 50.0%, an effective rate of 88.5%, a fungal clearance rate of 88.5%, and an adverse drug reaction rate of 4.8%; a miconazole cure rate of 35.8% and an effective rate of 88.7 %, The fungal clearance rate was 78.3%, and the incidence of adverse drug reactions was 4.7%. 1% terbinafine hydrochloride has good curative effect and high safety in treating impregnated and erosive superficial mycosis. A study abroad shows that terbinafine has a cure rate of 91% to 100% for nail ringworm, and toenail ringworm is 85% to 90%. A domestic study showed that terbinafine was 250 mg per day for 45 consecutive days to treat nail ringworm. The clinical cure rate was 33.3% when the drug was discontinued, and the mycological cure rate was 100%. The clinical cure rate and mycology after 90 days of discontinuation The cure rate was 100%, and occasional mild nausea did not affect continued treatment. Another study used intermittent therapy to treat onychomycosis, that is, oral terbinafine 250 mg daily for the first week, and 250 mg orally every other day after the second week. The course of nail fungus disease for young patients is 5 weeks, and the course of the elderly is 7 weeks. The course of mycotic disease was 11 weeks, and the curative effect was evaluated at 20 weeks. Results The clinical cure rates of 5 week therapy, 7 week therapy, and 11 week therapy were 87.9%, 89.6%, and 83.9%, and mycological cure rates were 95.9%, 95.7%, 94.9%. [3]
Terbinafine Specific Medicine Sheet
- The chemical name of terbinafine hydrochloride is (E) -N- (6,6-dimethyl-2-hepten-4-ynyl) -N-methyl-1-naphthylamide · hydrochloride . Molecular formula: C21H25N · HCl, molecular weight: 327.90.
- This product is a white tablet.
Terbinafine pharmacological effects
- Terbinafine is an acrylamine drug. Pathogenic fungi to the skin, hair, and nails include dermatophytes such as Trichophyton (such as Trichophyton rubrum, Trichophyton versicolor, Trichophyton verrucosa, Trichophyton hirsutum, Trichophyton purpura), Microsporum (such as Microsporum canis), Epidermophyton floccus, and yeasts of the genus Candida (such as Candida albicans) and Trichophyton furfur Fungal activity. Yeast has a bactericidal effect or a bacteriostatic effect depending on the species. Terbinafine specifically interferes with the early steps of fungal sterol biosynthesis, which causes a deficiency of ergosterol and the accumulation of squalene in the cell, which leads to the death of the fungal cells. Terbinafine works by inhibiting squalene epoxidase on the membrane of fungal cells. Squalene cyclooxygenase is not related to the cytochrome P450 system. Terbinafine does not affect the metabolism of hormones or other drugs.
- When administered orally, the concentration of the drug in the skin, hair and nails can reach a level of fungicidal activity.
Terbinafine pharmacokinetics
- A single oral dose of 250 mg terbinafine reached peak plasma in 2 hours at a concentration of 0.97 ug / mL. The absorption half-life is 0.8 hours and the distribution half-life is 4.6 hours. Food has a moderate effect on terbinafine's bioavailability, but there is no need to adjust dosage accordingly. Terbinafine binds tightly to plasma proteins (99%). It quickly diffuses through the dermis and accumulates in the lipophilic stratum corneum. Terbinafine can also be excreted through the sebaceous glands, resulting in high concentrations in the hair follicles, hair, and sebaceous skin. There is also evidence that terbinafine can be distributed to the deck within the first week after starting treatment.
- Terbinafine is rapidly and extensively metabolized by at least 7 CYP isomerases, including CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19. Biotransformed metabolites have no antifungal activity and are mainly excreted in urine. The terminal clearance half-life is 17 hours without evidence of accumulation in the body. Terbinafine's plasma steady-state concentration has no age-dependent change, but in patients with impaired liver or renal function, clearance may be reduced, which can cause terbinafine to increase plasma levels.
- For patients with liver disease, single-dose pharmacokinetic studies have shown that terbinafine's clearance is reduced by about 50%.
Terbinafine indications
- Fungal infections of the skin and hair caused by dermatophytes such as Trichophyton rubrum, Trichophyton rubrum, Trichophyton versicolor, Trichophyton versicolor, Microsporum canis and Epidermophyton floccus.
- This product is only used to treat large areas of severe skin infections caused by ringworm, tinea corporis, tinea pedis, tinea pedis, and candida (such as Candida albicans), based on the site of infection, severity and scope The need for oral administration.
- Dermatophyte (filamentous fungus) infection caused by onychomycosis.
Terbinafine usage and dosage
- Adjust the course of treatment according to the severity of the infection and indications.
- Adult: 250mg (1 tablet), once a day.
- Adolescents weighing> 40kg (usually> 12 years): 250mg (1 tablet) once a day.
- Candida albicans
- Children weighing> 20kg (usually age> 5 years): The data obtained from controlled trials in this group of patients are very limited, so the drug is only available when there is no alternative treatment option and the potential treatment benefit is greater than the possible danger Before use.
- Because there is no experience with oral terbinafine in children younger than 2 years of age, this product is not recommended for this age group.
- Skin infections-Recommended course of treatment: Athlete's foot (toe-toe, plantar / shoe type): 2-6 weeks.
- Tinea corporis, jock itch: 2-4 weeks.
- Skin candidiasis: 2-4 weeks.
- The disappearance of infection symptoms and signs may not appear until weeks after mycological cure.
- Hair and scalp infections-Recommended course of treatment: Tinea capitis: 4 weeks. Tinea capitis is mainly seen in children.
- Onychomycosis: For most patients, a successful course of treatment is 6-12 weeks.
- Nail mycosis: In most cases of nail mycosis, the course of treatment is 6 weeks.
- Toenail fungus disease: Most cases of toenail fungus infection, the treatment course is 12 weeks.
- Some patients with hypothyroidism require a longer course of treatment. Good clinical results are often seen after mycological cure and months after treatment is discontinued, which is related to the time required for healthy nail growth.
Terbinafine adverse reactions
- Occurrence Estimate: Very Common (greater than or equal to) 10%, 1% (smaller than or equal to) Common> 10%, 0.1% (smaller than or equal to) Uncommon> 1%, 0.01% (smaller than or equal to) rare> 0.1%, very rare> 0.01%.
- In general, terbinafine is well tolerated, and the adverse reactions are usually mild to moderate. The most common are gastrointestinal symptoms (fullness, decreased appetite, indigestion, nausea, mild abdominal pain, diarrhea), mild skin reactions (rash, urticaria), and skeletal muscle reactions (arthralgia, myalgia).
- Uncommon: Taste disorders, including loss of taste, often recover within weeks after discontinuation.
- Rare: Hepatobiliary dysfunction (actually primary cholestasis) associated with terbinafine treatment has been reported, including very rare liver failure.
- Very rare: severe skin reactions (such as Steven-Johnson syndrome, toxic epidermal necrosis) and allergic reactions have been reported. Terbinafine treatment should be discontinued if a progressive rash occurs.
- Very rare: Hematological disorders such as neutropenia, agranulocytosis, or thrombocytopenia have been reported.
- Very rare: hair loss has been reported, although the cause has not been determined.
Terbinafine Contraindications
- Those who are allergic to terbinafine hydrochloride and other ingredients of this product are contraindicated.
Terbinafine notes
- Patients with signs or symptoms suggestive of liver dysfunction, such as unexplained nausea, anorexia or fatigue, or jaundice, black urine, or colorless stool, should be confirmed to be of liver origin and discontinue terbinafine .
- Yeast
- Patients with renal impairment
- Patients with impaired liver function (creatinine clearance of less than 50 mL / min or blood creatinine of more than 300 mmol / L) should take half of the normal dose.
- In vitro studies have shown that terbinafine inhibits the metabolism of CYP2D6. Therefore, if the therapeutic window of drugs taken at the same time is narrow, the drugs that are mainly metabolized by this enzyme should be accepted, such as tricyclic antidepressants (TCAs), - Patients receiving concomitant therapy with blockers, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAO-Is) type B were monitored.
- Medication for pregnant women
- Animal studies of fetal toxicity and fertility found no adverse reactions. Because clinical experience in pregnant women is very limited, during pregnancy, if the benefits of taking the drug do not outweigh the risks, they should not be used. Terbinafine can be secreted into milk; therefore, mothers treated with terbinafine should not breastfeed.
- Medication for pediatric patients
- Children over 2 years of age are better tolerated by oral terbinafine.
- Medication for elderly patients
- There is no evidence that elderly patients and young patients need to take different doses or have different adverse reactions. When prescribing, the possibility of liver and kidney damage in patients in this age group should be considered.
Terbinafine interaction
- According to the results of in vitro studies and studies performed in healthy volunteers, terbinafine has slightly inhibited or increased the elimination of most drugs metabolized by the cytochrome P450 system (such as cyclosporine, terfenadine, triazoles, P-toluenesulfonylurea or oral contraceptives).
- However, in vitro studies have shown that terbinafine inhibits CYP2D6-mediated metabolism. The findings of this in vitro experiment may have clinical relevance to compounds that are primarily metabolized by this enzyme, such as tricyclic antidepressants (TCAs), -Blockers, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAO-Is) type B because they also have narrow therapeutic windows. In patients who have taken terbinafine in combination with oral contraceptives, cases of irregular menstruation have been reported, although their incidence is still within that of patients taking oral contraceptives alone. On the other hand, some metabolism-inducing drugs (such as rifampicin) can speed up the plasma clearance of terbinafine, while other drugs that inhibit cytochrome P450 (such as cimetidine) can inhibit the plasma of terbinafine Clear. If it is necessary to use these drugs at the same time, the dose of terbinafine should be adjusted accordingly.
Terbinafine overdose
- A few cases of overdose (up to 5 g) have been reported with headache, nausea, epigastric pain, and dizziness.
- The recommended treatment for overdose is to clear the drug, mainly by taking activated carbon for treatment, and supportive treatment can be given according to the symptoms.
- Storage / Expiry date Sealed, protected from light, stored below 30 ° C. The validity period is tentatively set for 3 years. [4]