What Is Fluconazole?

Fluconazole is a drug for the treatment of fungal infections. It is a broad-spectrum antifungal drug and has a therapeutic effect on fungal infections in humans and animals. At present, there are several dosage forms of tablets, capsules, powder injections and injections on the market [1 ] .

Fluconazole is a drug for the treatment of fungal infections. It is a broad-spectrum antifungal drug and has a therapeutic effect on fungal infections in humans and animals. At present, there are several dosage forms of tablets, capsules, powder injections and injections on the market [1 ] .
Chinese name
Fluconazole
Foreign name
Fluconazole (Diflucan)
Molecular formula
C13H12F2N6O
Drug type
Antifungal

Introduction to Fluconazole Compounds

Fluconazole Basic Information

Chinese name: Fluconazole
Chinese alias: - (2,4-difluorophenyl) -- (1H-1,2,4-triazol-1-ylmethyl) -1H-1,2,4-triazole-1- Ethyl alcohol; 2- (2,4-difluorophenyl) -1,3-bis (1H-1,2,4-triazol-1-yl) -2-propanol; Dafukang; manifen McDonnell Flucon
English name: fluconazole
English alias: Flunazol; Difluean; Elazor; Fluconazole; Flusol; -triazole-1-ethanol
CAS number: 86386-73-4
Molecular formula: C 13 H 12 F 2 N 6 O
Molecular weight: 306.27100
Structural formula:
Exact mass: 306.10400
PSA: 81.65000
LogP: 0.73580

Fluconazole physicochemical properties

Appearance and properties: white or off-white crystalline powder, odorless or slightly odor-specific, bitter. The product is soluble in methanol, soluble in ethanol, slightly soluble in dichloromethane, water or acetic acid, and insoluble in ether.
Density: 1.49 g / cm 3
Melting point: 138-140 ° C
Boiling point: 579.8ºC at 760 mmHg
Flash point: 304.4ºC
Storage conditions: -20ºC

Fluconazole Safety Information

Symbol: GHS07
Signal Word: Warning
Hazard statement: H302; H315; H319; H335
Cautionary statement: P261; P305 + P351 + P338
Customs code: 2933990090
Danger category code: R36 / 37/38
Safety instructions: S26; S36 / 37/39; S24 / 25
RTECS number: XZ4810000
Dangerous goods sign: Xn

Fluconazole production method

Method 1: 1H-1,2,4-triazole can be obtained from formamide, hydrazine hydrate and 85% formic acid. From m-phenylenediamine, m-difluorobenzene can be obtained, and then brominated to obtain 2,4-difluorobromobenzene. Magnesium was dissolved in anhydrous diethyl ether, and a diethyl ether solution of 2,4-difluorobromobenzene was added dropwise under ultrasonic irradiation. Then, an ether solution of 1,3-dichloroacetone was added dropwise under cooling in an ice bath, and the mixture was stirred at room temperature overnight. Add glacial acetic acid and water. The separated organic layer was dried and concentrated. The concentrated solution, triazole, potassium carbonate and PEG600 were dissolved in dry ethyl acetate and refluxed. Filter, wash with water until neutral, and dry. The solvent was evaporated, and ethyl acetate-cyclohexane (1: 1) was recrystallized to obtain fluconazole. The total yield was 33.6%, and the melting point was 138.5-140 ° C. The last step can also be performed in propionitrile. 1,3-dihalo (x = Br or Cl) -2- (2,4-difluorophenyl) -2-propanol and 1H-1,2,4-triazole in propionitrile, catalyzed by sodium hydroxide Crude fluconazole can be obtained by refluxing with PEG 600 under phase transfer catalysis. The crude product is soluble in fatty alcohols (such as propanol, isopropanol or butanol, etc.), heated to dissolve, decolorized with a small amount of activated carbon, and cooled to obtain crystals, which are fluconazole products with a melting point of 139-140 ° C.
Method 2: Grignard reagents of methyl 2,4-difluorobenzoate and 1-chloromethyl-1,2,4-triazole are reacted and hydrolyzed to obtain fluconazole.

Fluconazole uses

Fluconazole is a fluorotriazole antifungal drug [2] .

Fluconazole Pharmacopoeia Standard

Fluconazole source (name), content (potency)

This product is - (2,4-difluorophenyl) -- (1H-1,2,4-triazol-1-ylmethyl) -1H-1,2,4-triazole-1- Based ethanol. Calculated on dry basis, containing C 13 H 12 F 2 N 6 O shall not be less than 98.5%.

Fluconazole traits

This product is white or off-white crystal or crystalline powder; it is odorless or slightly odor-specific and bitter.
This product is soluble in methanol, soluble in ethanol, slightly soluble in dichloromethane, water or acetic acid, and insoluble in ether.
Melting point
The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 137 to 141 ° C.

Fluconazole identification

(1) Take this product, add ethanol to dissolve and dilute it to make a solution containing about 0.2mg per 1ml, and measure according to UV-Vis spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 Edition). Maximum absorption with minimum absorption at a wavelength of 264 nm.
(2) The infrared light absorption spectrum of this product should be consistent with the control spectrum (Figure 893 of "Infrared Spectra of Drugs").
(3) Identification reaction of organic fluoride in this product (Appendix III of Part Two of the Pharmacopoeia, 2010 Edition).

Fluconazole test

Clarity of the solution
Take 20mg of this product and add 10ml of water to dissolve. The solution should be clear; if it is turbid, it should not be more concentrated (for injection) compared with the turbidity standard solution No. 1 (Appendix B of Part Two of the 2010 Pharmacopoeia).
fluorine
Take about 15mg of this product, weigh it accurately, and determine it according to the fluorine inspection method (Appendix E of the second edition of the Pharmacopoeia, 2010 edition). The fluorine content should be 11.1% to 12.4%.
relative substance
Take this product, add the mobile phase to dissolve and dilute it to make a solution containing about 1mg per 1ml as the test solution; take 1ml precisely, place it in a 100ml measuring bottle, dilute to the mark with the mobile phase, shake well, and use it as a control Solution. According to HPLC (Appendix VD of Part Two of the Pharmacopoeia, 2010 edition), octadecylsilane bonded silica gel was used as the filler; methanol-phosphate buffer solution (pH 7.0) (45:55) was used as the mobile phase; The detection wavelength was 260 nm. The theoretical plate number is calculated to be not less than 2000 by fluconazole peak. Take 10 l of the control solution and inject it into the liquid chromatograph to adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full scale. Precisely measure 20 l each of the test solution and the control solution, and respectively inject them into the liquid chromatograph, and record the chromatogram to twice the retention time of the main component peak. If there is an impurity peak in the chromatogram of the test solution, the sum of the area of each impurity peak must not be greater than the area of the main peak of the control solution (1.0%).
Chlorinated compounds
Take about 20mg of this product, weigh it accurately, and perform organic destruction according to the oxygen bottle combustion method (Appendix C of the second edition of the Pharmacopoeia 2010), using 20ml of 0.4% sodium hydroxide solution as the absorption solution. After the absorption of is complete, shake vigorously for 5 minutes. Add 10ml of dilute nitric acid, transfer to 50ml Nass colorimetric tube, check according to the chloride inspection method (Appendix A of Pharmacopoeia Part II of the 2010 edition), and check with the control solution (same method as the test product, but in the filter paper when burning) It does not contain the test product, and compared with the standard sodium chloride solution (6.0ml), it must not be more concentrated (0.3%).
Loss on drying
Take this product and dry it to constant weight at 105 ° C, and the weight loss shall not exceed 0.5% (Appendix L of Pharmacopoeia Part II of 2010 Edition).
Residue on ignition
Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.
Heavy metal
Take the residue left under the item of burning residue and check it according to law (Appendix H of the second edition of the Pharmacopoeia of 2010 Edition, the second method H), the content of heavy metals must not exceed 20 parts per million.

Determination of fluconazole

Take about 0.1g of this product, accurately weigh it, add 50ml of glacial acetic acid to dissolve it, and then titrate with potentiometric titration method (Appendix A of Pharmacopoeia, Part II of the 2010 edition), titrate with perchloric acid (0.1mol / L), and titrate The results are corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 15.31mg of C 13 H 12 F 2 N 6 O [3-4] .

Fluconazole category

Antifungal.

Fluconazole storage

Sealed and stored in a dry place.

Fluconazole preparations

(1) Fluconazole tablets (2) Fluconazole capsules (3) Fluconazole sodium chloride injection

Fluconazole Drug Analysis

Method Name: Fluconazole Determination-Potentiometric Titration
Application: This method uses the titration method to determine the content of fluconazole.
This method is applicable to fluconazole.
Principle of the method: Put the test product in an Erlenmeyer flask, dissolve it with glacial acetic acid, and titrate with a perchloric acid titration solution (0.1mol / L) according to the potentiometric titration method. Read out the amount of perchloric acid titrant used to calculate the content of fluconazole.
Reagent:
1. Water (newly boiled to room temperature)
2. Perchloric acid titrant (0.1mol / L)
3. Crystal violet indicator liquid
4. Anhydrous glacial acetic acid
5. Reference potassium phthalate
equipment:
Sample preparation:
1. Perchloric acid titration solution (0.1mol / L)
Preparation: Take 750mL of anhydrous glacial acetic acid (calculated with water content, add 5.22mL acetic anhydride per 1g of water), add 8.5mL perchloric acid (70% -72%), shake well, and slowly add acetic anhydride dropwise at room temperature. 23mL, shake while adding, shake evenly after adding, let cool, add an appropriate amount of anhydrous glacial acetic acid to 1000mL, shake well, and leave for 24 hours. If the test sample is easily acetylated, the water content on this page must be determined by moisture measurement, and then the water content of this solution should be adjusted to 0.01% -0.2% with water and acetic anhydride.
Calibration: Take about 0.16g of standard potassium hydrogen phthalate dried to constant weight at 105 , accurately weigh, add 20mL of anhydrous glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and titrate slowly with Blue, and the results of the titration are corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.
Storage: Place in a brown glass bottle and keep tightly closed.
Crystal violet indicator liquid
Take 0.5g of crystal violet, add 100mL of glacial acetic acid to dissolve, and get.
Operation steps: accurately weigh about 0.1g of the test sample, place it in a conical flask, add 50mL of glacial acetic acid to dissolve it, and then titrate with the perchloric acid titration solution (0.1mol / L) according to the potentiometric titration method. Blank test correction. Record the volume (mL) of perchloric acid titrant consumed. Each 1mL of perchloric acid titrant (0.1mol / L) is equivalent to 15.31mg of C13H12F2N6O.
Note: "Precise weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision weighing" means that the accuracy of the measured volume should meet the accuracy of the pipette in the national standard Requirement [5] .

Fluconazole drug description

Fluconazole Pharmacology and Toxicology

1. Pharmacology This product is a pyrrole antifungal. Broad antifungal spectrum. Oral and intravenous injection of the product to human and various animal fungal infections, such as candidiasis (including systemic candidiasis in normal or immunocompromised humans and animals), new cryptococcus infections (including intracranial infections), Malassezia furfur, Microsporidium, Trichophyton, Epidermophyton, Dermatitis, Coccosporium (including intracranial infections), and capsular histoplasma, Phaeophilus, K. Cladosporium is effective. The in vitro antibacterial activity of this product is significantly lower than that of ketoconazole, but the in vivo antibacterial activity of this product is significantly higher than the in vitro effect. The mechanism of action of this product is mainly to highly selectively interfere with the activity of fungal cytochrome P-450, thereby inhibiting the biosynthesis of ergosterol on the fungal cell membrane.
2. Toxicology This product is highly selective for fungal-dependent cytochrome P-450 enzymes. Taking the product 0.5g a day for 28 consecutive days has proven to have no effect on the plasma testosterone concentration of men and the steroid hormone concentration of women of childbearing age.

Fluconazole pharmacokinetics

Oral absorption is good, and is not affected by food, antacids, H2 receptor blockers. About 90% of the dosage can be absorbed by oral administration on an empty stomach. A single oral dose of 100mg of this product, the average peak blood concentration (Cmax) of 4.5 ~ 8mg / L. The apparent distribution volume (Vd) is close to the total amount of water in the body. The plasma protein binding rate of this product is low (11% ~ 12%). It is widely distributed in the body, such as skin, blister fluid, peritoneal fluid, sputum and other body fluids. The drug concentration in urine and skin is about 10 times the blood concentration. ; About 2 times in blister skin; close to blood concentration in saliva, sputum, blister fluid, nails; when meningitis is inflamed, the concentration of this product in cerebrospinal fluid can reach 54% to 85% of blood concentration. This product is metabolized in the liver in small amounts. It is mainly excreted from the kidney, and more than 80% of the dosage is excreted from the urine in the original form. The blood elimination half-life (t1 / 2?) Is 27 to 37 hours, and it is significantly prolonged when renal function declines. Hemodialysis or peritoneal dialysis can partially clear the product.

Fluconazole drug interactions

1. When this product is combined with isoniazid or rifampicin, the concentration of this product can be reduced.
2. When this product is used in combination with sulfonylurea, such as tolbutamide, chlorobutamide, and glipizide, it can increase the blood concentration of such drugs and may cause hypoglycemia, so it is necessary to monitor blood glucose. And reduce the dose of sulfonylurea hypoglycemic drugs.
3 When combined with cyclosporine at high doses, the plasma concentration of cyclosporine can be increased, which increases the risk of toxic reactions. Therefore, caution must be taken when monitoring the cyclosporine plasma concentration and adjusting the dose. application.
4 The combination of this product with hydrochlorothiazide can increase the blood concentration of this product.
5. When the product is combined with theophylline, the theophylline blood concentration can increase by about 13%, which can cause toxic reactions. Therefore, the blood concentration of theophylline needs to be monitored.
6. When this product is used in combination with dicoumarin anticoagulants such as warfarin, it can enhance the anticoagulant effect of dicoumarin anticoagulants, leading to prolonged prothrombin time, so prothrombin time should be monitored and used with caution .
7. When this product is combined with phenytoin sodium, the blood concentration of phenytoin sodium can be increased, so the blood concentration of phenytoin sodium needs to be monitored.

Fluconazole effects and uses

Fluconazole injection
This product is a fluorotriazole antifungal drug. Its antibacterial spectrum is similar to that of ketoconazole, and its antibacterial activity is stronger than that of ketoconazole. Its mechanism of action is to inhibit ergosterol synthetase, an essential component of fungal cell membranes, hinder ergosterol synthesis, destroy the integrity of fungal cell walls, and inhibit its growth and reproduction. This product has strong antibacterial activity against Candida albicans, large and small spores, new cryptococcus, epidermal ringworm and capsular histoplasma. Good oral absorption, widely distributed in the body, can penetrate into the cerebrospinal fluid. It is mainly used for vaginal candidiasis, thrush, atrophic oral candidiasis, fungal meningitis, pulmonary fungal infections, abdominal infections, urinary tract infections, and skin fungal infections.

Fluconazole dosage

Oral, candidiasis and dermatomycosis, 50mg ~ 100mg / time, once / day. Vaginal candidiasis 150mg / time, once / day. For the treatment of cryptococcal meningitis and other infections, the usual dose is 400 mg on the first day, followed by 200 mg to 400 mg / day. Children should be used with caution.
Medication for pregnant women
1. In animal tests, changes in abortion, stillbirth, rib deformities, and cleft palate in juvenile animals may occur when the product is given in high doses. Although such cases are not found in humans, pregnant women should still be disabled.
2. There is no data on the concentration of this product in breast milk, so breastfeeding women use it with caution or suspend breastfeeding when taking this product.
Medication for children and the elderly
There is insufficient research data on the effects of this product on children. Although a small number of pediatric patients aged 2 weeks to 14 years of age have no adverse reactions when treated with daily doses of 3 to 6 mg / kg (by weight), they are still not suitable for children.
Medication for elderly patients
There is no need to adjust the dose in elderly patients with impaired renal function. Elderly patients with impaired renal function must adjust the dose according to creatinine clearance (see Dosage and Administration for details).

Fluconazole indications

This product is mainly used in patients with severe illness in the following indications:
  1. Candidiasis: used to treat oropharyngeal and esophageal candidiasis; disseminated candidiasis, including candida vulvovaginitis such as peritonitis, pneumonia, and urinary tract infections. It can still be used to prevent the occurrence of Candida infection when patients with bone marrow transplantation receive cytotoxic drugs or radiation therapy.
  2. Cryptococcal disease: It is used to treat new types of cryptococcus other than meninges. In the treatment of cryptococcal meningitis, this product can be used as a maintenance treatment after amphotericin B combined with flucytosine.
  3. Coccidioidomycosis.
  4. This product can also replace itraconazole for the treatment of blastomycosis and histoplasmosis.

Fluconazole adverse reactions

1. Common gastrointestinal reactions include nausea, vomiting, abdominal pain or diarrhea.
2. Allergic reactions: can manifest as a rash, occasionally severe exfoliative dermatitis (often accompanied by liver damage), exudative polymorphic erythema.
3. Hepatotoxicity: During the treatment, mild transient serum aminotransferase elevation may occur, and hepatotoxicity symptoms may occasionally occur, especially in patients with severe underlying diseases (such as AIDS and cancer).
4. Visible headache and dizziness.
5. Some patients, especially those with severe underlying diseases (such as AIDS and cancer), may have abnormal kidney function.
6. Occasionally, changes in blood tests such as transient neutropenia and thrombocytopenia may occur in peripheral blood, especially in patients with severe underlying diseases (such as AIDS and cancer).

Other effects of fluconazole

Treatment of onychomycosis once a week, 150mg once can usually be cured in about four months.

Fluconazole precautions

1. This product can have cross-allergic reactions with other pyrrole drugs, so those who are allergic to any kind of pyrrole drugs should not use this product.
2. Because the product is mainly excreted from the kidney, renal function should be checked regularly during the treatment of patients with impaired renal function.
3 The course of application of this product should depend on the site of infection and individual response to treatment. The general treatment should be continued until the clinical manifestations of the fungal infection and laboratory indicators indicate the disappearance of the fungal infection. Cryptococcal meningitis or AIDS patients with recurrent oropharyngeal candidiasis need long-term maintenance treatment with this product to prevent recurrence.
4 For patients receiving bone marrow transplantation, if severe granulocytopenia has occurred in advance, the product should be used prophylactically, until 7 days after the neutrophil count rises above 1 × 109 / L.
5. For patients with impaired renal function, the dosage can be adjusted according to the aforementioned scheme (see Dosage and Administration); hemodialysis patients can be given one day after each dialysis, because 3 hours of hemodialysis can reduce the blood concentration of the product by about 50 %.

Fluconazole preparations

Fluconazole tablets
[Main Ingredients] Fluconazole
[Drug specifications] 50mg
[Indications] 1. Candidiasis: used to treat oropharyngeal and esophageal candidiasis; disseminated candidiasis, including peritonitis, pneumonia, and urinary tract infections; candida vulvovaginitis. It can still be used to prevent the occurrence of Candida infection when patients with bone marrow transplantation receive cytotoxic drugs or radiation therapy. 2. Cryptococcosis: It is used to treat new types of cryptococcosis other than meninges. When treating cryptococcus meningitis, this product can be used as a maintenance treatment drug after amphotericin B combined with flucytosine. 3 Coccidioidomycosis. 4 Preventive treatment for patients receiving chemotherapy, radiotherapy and immunosuppressive therapy. 5. This product can also replace itraconazole for the treatment of blastomycosis and histoplasmosis.
[Usage and Dosage] Oral. Adults (1) disseminated candidiasis: the first dose is 0.4g, the next dose is 0.2g, once a day for at least 4 weeks, and the symptoms last for at least 2 weeks. (2) Esophageal candidiasis: The first dose is 0.2 g, the next dose is 0.1 g, once a day for at least 3 weeks, and the symptoms last for at least 2 weeks. According to the treatment response, the dose can be increased to 0.4g once a day. (3) Oropharyngeal candidiasis: the first dose is 0.2g, and the next dose is 0.1g, once a day, and the course of treatment is at least 2 weeks. (4) Candida vulvovaginitis: single dose, 0.15g.
[Pharmacology and Toxicology]
1. Pharmacology
This product is a pyrrole antifungal. Broad antifungal spectrum. Oral and intravenous injection of this product to human and various animal fungal infections, such as candidiasis (including systemic candidiasis in normal or immunocompromised humans and animals), new cryptococcus infections (including intracranial infections), Malassezia furfur, Microsporidium, Trichophyton, Epidermophyton, Dermatitis, Coccosporium (including intracranial infections), and capsular histoplasma, Phaeophilus, K. Cladosporium is effective. The in vitro antibacterial activity of this product is significantly lower than that of ketoconazole, but the in vivo antibacterial activity of this product is significantly higher than the in vitro effect.
The mechanism of action of this product is mainly to highly selectively interfere with the fungal cytochrome P-450 activity, thereby inhibiting the biosynthesis of ergosterol on the fungal cell membrane.
2. Toxicology This product is highly selective for fungal-dependent cytochrome P-450 enzymes. Taking this product 0.5g a day for 28 consecutive days has proven to have no effect on the plasma testosterone concentration of men and the steroid hormone concentration of women of childbearing age.
Adverse reactions
1. Common gastrointestinal reactions include nausea, vomiting, abdominal pain or diarrhea. 2. Allergic reactions: can manifest as a rash, occasionally severe exfoliative dermatitis (often accompanied by liver damage), exudative polymorphic erythema. 3 Hepatotoxicity: Mild transient serum aminotransferase elevations can occur during treatment and occasional hepatotoxic symptoms, especially in patients with severe underlying diseases such as AIDS and cancer. 4 Dizziness and headache are visible. 5. Some patients, especially those with severe underlying diseases such as AIDS and cancer, may develop abnormal kidney function. 6. Occasionally, hematological changes such as transient neutropenia and thrombocytopenia may occur in peripheral blood, especially in patients with severe underlying diseases (such as AIDS and cancer).
Precautions
1. This product can cross-allergic with other pyrrole drugs, so those who are allergic to any kind of pyrrole drugs should not use this product. 2. Because this product is mainly excreted from the kidneys, renal function needs to be checked regularly during treatment. It should be used in patients with reduced renal function. 3 This product's current long-term preventive medication in immunodeficiency patients has led to increased resistance to pyrrole antifungal drugs such as fluconazole and other Candida species, so it is necessary to grasp the indications to avoid unindicated preventive medications. 4 During the course of treatment, mild transient aminotransferase elevations may occur, and hepatotoxic symptoms may occasionally occur. Therefore, liver function should be checked regularly before and during treatment with this product. If there is a persistent abnormality in liver function or clinical symptoms of liver toxicity, this product should be discontinued immediately. 5. When this product is used in combination with hepatotoxic drugs, if you take this product for more than two weeks or receive more than the usual dose of this product, it can increase the incidence of hepatotoxicity, so you need to observe closely, before and during the treatment every two weeks Have a liver function test. 6. The course of application of this product should depend on the site of infection and individual response to treatment. The general treatment should be continued until the clinical manifestations of the fungal infection and laboratory indicators indicate the disappearance of the fungal infection. Cryptococcal meningitis or recurrent oropharyngeal candidiasis patients with AIDS need long-term maintenance treatment with this product to prevent recurrence. 7. For patients receiving bone marrow transplantation, if severe granulocytopenia has occurred in advance, this product should be used prophylactically until the neutrophil count rises above 1 × 109 / L 7 days later. 8. For patients with impaired renal function, the dosage can be adjusted according to the aforementioned scheme (see [Usage and Dosage]); hemodialysis patients can give this product one day after each dialysis, because 3 hours of hemodialysis can reduce the blood concentration of this product About 50%. [6]
Fluconazole capsules
[Drug type] antifungal
[Drug specifications] 50mg
[Indications] This product is mainly used for patients with severe illness in the following indications: 1. Candidiasis: used to treat oropharyngeal and esophageal candidiasis; disseminated candidiasis, including peritonitis, pneumonia, and urinary tract infections; candida vulvovaginitis. It can still be used to prevent the occurrence of Candida infection when patients with bone marrow transplantation receive cytotoxic drugs or radiation therapy. 2. Cryptococcosis: It is used to treat new types of cryptococcosis other than meninges. When treating cryptococcus meningitis, this product can be used as a maintenance treatment drug after amphotericin B combined with flucytosine. 3 Coccidioidomycosis. 4 Preventive treatment for patients receiving chemotherapy, radiotherapy and immunosuppressive therapy. 5. This product can also replace itraconazole for the treatment of blastomycosis and histoplasmosis.
[Usage and Dosage] Oral. Adults (1) disseminated candidiasis: the first dose is 0.4g, the next dose is 0.2g, once a day for at least 4 weeks, and the symptoms last for at least 2 weeks. (2) Esophageal candidiasis: The first dose is 0.2 g, the next dose is 0.1 g, once a day for at least 3 weeks, and the symptoms last for at least 2 weeks. According to the treatment response, the dose can be increased to 0.4g once a day. (3) Oropharyngeal candidiasis: the first dose is 0.2g, and the next dose is 0.1g, once a day, and the course of treatment is at least 2 weeks. (4) Candida vulvovaginitis: single dose, 0.15g.
[Pharmacology and Toxicology]
1. Pharmacology This product is a pyrrole antifungal. Broad antifungal spectrum. Oral and intravenous injection of this product to human and various animal fungal infections, such as candidiasis (including systemic candidiasis in normal or immunocompromised humans and animals), new cryptococcus infections (including intracranial infections), Malassezia furfur, Microsporidium, Trichophyton, Epidermophyton, Dermatitis, Coccosporium (including intracranial infections), and capsular histoplasma, Phaeophilus, K. Cladosporium is effective. The in vitro antibacterial activity of this product is significantly lower than that of ketoconazole, but the in vivo antibacterial activity of this product is significantly higher than the in vitro effect. The mechanism of action of this product is mainly to highly selectively interfere with the fungal cytochrome P-450 activity, thereby inhibiting the biosynthesis of ergosterol on the fungal cell membrane. 2. Toxicology This product is highly selective for fungal-dependent cytochrome P-450 enzymes. Taking 0.5g of this product a day for 28 consecutive days has proven to have no effect on the plasma testosterone concentration of men and the steroid hormone concentration of women of childbearing age.
Adverse reactions
1. Common gastrointestinal reactions include nausea, vomiting, abdominal pain or diarrhea. 2. Allergic reactions: can manifest as a rash, occasionally severe exfoliative dermatitis (often accompanied by liver damage), exudative polymorphic erythema. 3 Hepatotoxicity: Mild transient serum aminotransferase elevations can occur during treatment and occasional hepatotoxic symptoms, especially in patients with severe underlying diseases such as AIDS and cancer. 4 Dizziness and headache are visible. 5. Some patients, especially those with severe underlying diseases such as AIDS and cancer, may develop abnormal kidney function. 6. Occasionally, hematological changes such as transient neutropenia and thrombocytopenia may occur in peripheral blood, especially in patients with severe underlying diseases (such as AIDS and cancer).
Precautions
1. This product can cross-allergic with other pyrrole drugs, so those who are allergic to any kind of pyrrole drugs should not use this product. 2. Because this product is mainly excreted from the kidneys, renal function needs to be checked regularly during treatment. It should be used in patients with reduced renal function. 3 This product's current long-term preventive medication in immunodeficiency patients has led to increased resistance to pyrrole antifungal drugs such as fluconazole and other Candida species, so it is necessary to grasp the indications to avoid unindicated preventive medications. 4 During the course of treatment, mild transient aminotransferase elevations may occur, and hepatotoxic symptoms may occasionally occur. Therefore, liver function should be checked regularly before and during treatment with this product. If there is a persistent abnormality in liver function or clinical symptoms of liver toxicity, this product should be discontinued immediately. 5. When this product is used in combination with hepatotoxic drugs, if you take this product for more than two weeks or receive more than the usual dose of this product, it can increase the incidence of hepatotoxicity, so you need to observe closely, before and during the treatment every two weeks Have a liver function test. 6. The course of application of this product should depend on the site of infection and individual response to treatment. The general treatment should be continued until the clinical manifestations of the fungal infection and laboratory indicators indicate the disappearance of the fungal infection. Cryptococcal meningitis or recurrent oropharyngeal candidiasis patients with AIDS need long-term maintenance treatment with this product to prevent recurrence. 7. For patients receiving bone marrow transplantation, if severe granulocytopenia has occurred in advance, this product should be used prophylactically until the neutrophil count rises above 1 × 109 / L 7 days later. 8. For patients with impaired renal function, the dosage can be adjusted according to the aforementioned scheme (see [Usage and Dosage]); hemodialysis patients can give this product one day after each dialysis, because 3 hours of hemodialysis can reduce the blood concentration of this product About 50%. [7]
Injection
[Main ingredients] This product is a compound preparation. Its components are: fluconazole and sodium chloride. Each bottle contains 0.2 g of fluconazole and 0.9 g of sodium chloride. The auxiliary material is water for injection.
[Drug specifications] 100ml: 0.2g
[Indications] This product is mainly used in patients with severe illness in the following indications: 1. Candidiasis: used to treat oropharyngeal and esophageal candidiasis; disseminated candidiasis, including peritonitis, pneumonia, and urinary tract infections; candida vulvovaginitis. It can still be used to prevent the occurrence of Candida infection when patients with bone marrow transplantation receive cytotoxic drugs or radiation therapy. 2. Cryptococcosis: It is used to treat new types of cryptococcosis other than meninges. When treating cryptococcus meningitis, this product can be used as a maintenance treatment drug after amphotericin B combined with flucytosine. 3 Coccidioidomycosis. 4 This product can also replace itraconazole for the treatment of blastomycosis and histoplasmosis.
Dosage
Intravenous infusion, the maximum infusion rate is about 200mg / hour.
[Pharmacology and Toxicology]
100 mg of this product was given intravenously, and the average peak drug concentration (Cmax) was 4.5 to 8 mg / L. The apparent distribution volume (Vd) is close to the total amount of water in the body. The plasma protein binding rate of this product is low (11% ~ 12%). It is widely distributed in the body, such as skin, blister fluid, peritoneal fluid, sputum and other body fluids. The drug concentration in urine and skin is about 10 times the blood drug concentration. ; About 2 times in blister skin; close to blood concentration in saliva, sputum, blister fluid, nails; when meningitis is inflamed, the concentration of this product in cerebrospinal fluid can reach 54% to 85% of blood concentration. A small amount of this product is metabolized in the liver. It is mainly excreted from the kidney, and the amount of the drug excreted from the urine in the original form accounts for more than 80% of the dose. The blood elimination half-life (t1 / 2) is 27 to 37 hours, which is significantly prolonged when renal function declines.
Adverse reactions
1. Common gastrointestinal reactions include nausea, vomiting, abdominal pain or diarrhea. 2. Allergic reactions: can manifest as a rash, occasionally severe exfoliative dermatitis (often accompanied by liver damage), exudative polymorphic erythema. 3 Hepatotoxicity: During the treatment, mild transient serum aminotransferase elevations may occur, and hepatotoxicity symptoms may occasionally occur, especially in patients with severe underlying diseases (such as AIDS and cancer). 4 Visible headache, dizziness. 5. Some patients, especially those with severe underlying diseases such as AIDS and cancer, may develop abnormal kidney function. 6. Occasionally, peripheral blood like transient neutropenia and thrombocytopenia may occur
Precautions
1. This product can cross-allergic with other pyrrole drugs, so those who are allergic to any kind of pyrrole drugs should not use this product. 2. Because this product is mainly excreted from the kidneys, renal function needs to be checked regularly during treatment. It should be used in patients with reduced renal function. 3 This product's current long-term preventive medication in immunodeficiency patients has led to increased resistance to pyrrole antifungal drugs such as fluconazole and other Candida species, so it is necessary to grasp the indications to avoid unindicated preventive medications. 4 During the course of treatment, mild transient aminotransferase elevations may occur, and hepatotoxic symptoms may occasionally occur. Therefore, liver function should be checked regularly before and during treatment with this product. If there is a persistent abnormality in liver function or clinical symptoms of liver toxicity, this product should be discontinued immediately. 5. When this product is used in combination with hepatotoxic drugs, if you take this product for more than two weeks or receive more than the usual dose of this product, it can increase the incidence of liver toxicity, which requires close observation. It should be performed every two weeks before and during the treatment. A liver function test. 6. The course of application of this product should depend on the site of infection and individual response to treatment. General treatment should continue until the clinical manifestations of the fungal infection and laboratory examination indicators show that the fungal infection disappears. Cryptococcal meningitis or AIDS patients with recurrent oropharyngeal candidiasis need long-term maintenance treatment with this product to prevent recurrence. 7. For patients receiving bone marrow transplantation, if severe granulocytopenia has occurred in advance, this product should be used prophylactically until the neutrophil count rises above 1 × 109 / L 7 days later. 8. For patients with impaired renal function, the dosage can be adjusted according to the aforementioned scheme (see [Usage and Dosage]); hemodialysis patients can give this product one day after each dialysis, because 3 hours of hemodialysis can reduce the blood concentration of this product About 5 [8]

Fluconazole manufacturer

Lunan Pharmaceutical Group, Jinan Zhongke Yitong Chemical Co., Ltd., Harbin Huarui Biochemical Pharmaceutical Co., Ltd. Shanxi Jinhuahuixing Pharmaceutical Co., Ltd., Hainan Mankexing Pharmaceutical Co., Ltd., Changzhou Lanling Pharmaceutical Co., Ltd., Henan Tianfang Pharmaceutical Co., Ltd. Co., Ltd., Beijing Huajin Pharmaceutical Co., Ltd., Jiangsu Jichuan Pharmaceutical Co., Ltd., Henan Shuaike Pharmaceutical Co., Ltd., Shandong Lukangchen New Pharmaceutical Co., Ltd., Jiangsu Changjiang Pharmaceutical Co., Ltd., Shandong Kangning Pharmaceutical Co., Ltd., Fujian Province Longyan Tianquan Biochemical Pharmaceutical, Hainan Tianwang International Pharmaceutical Co., Ltd., Hainan Tianfeng Pharmaceutical Co., Ltd., Hainan Changan International Pharmaceutical Co., Ltd., Guangdong Taishen Group Co., Ltd., Guangdong Taishen Group Licheng Pharmaceutical Factory, Wuhan Binhu Shuanghe Medicine Industry Co., Ltd., Henan Zhulin Zhongsheng Pharmaceutical Co., Ltd., Fujian Anxi Pharmaceutical Co., Ltd., Shandong Weifang Pharmaceutical Factory Co., Ltd., Shandong Hualu Pharmaceutical Co., Ltd., Anhui Global Pharmaceutical Co., Ltd., Outokang Pharmaceutical Group Co., Ltd., Suzhou Long MarchXinkai Pharmaceutical Co., Ltd., Shandong Luyin Medical Limited.

IN OTHER LANGUAGES

Was this article helpful? Thanks for the feedback Thanks for the feedback

How can we help? How can we help?

RELATED ARTICLES