[Properties] This product is a colorless, clear liquid.
This product is mainly used for patients with severe illness among the following indications;
1. Candidiasis: used to treat oropharyngeal and esophageal candida infections; disseminated candidiasis, including peritonitis, pneumonia, urinary tract infections, etc.; Candida vulvovaginitis. It can still be used to prevent Candida infection when bone marrow transplant patients receive cytotoxic drugs or radiotherapy.
2. Cryptococcosis: It is used to treat cryptococcal disease other than meninges; when treating cryptococcal meningitis, this product can be used as a maintenance treatment of amphotericin B combined with flucytosine after initial treatment.
4. This product can also replace itraconazole for the treatment of blastomycosis and histoplasmosis.
[Specifications] 100ml: 0.2g fluconazole and 0.9g sodium chloride
【Usage and Dosage】Intravenous drip, the drip time per 100ml (0.2g) is 30-60 minutes. Adults (1) Disseminated candidiasis: the first dose is 0.4g, the next 0.2g, once a day, for 4 weeks, and at least 2 weeks after the symptoms are relieved. (2) Esophageal candidiasis: the first dose is 0.2g, the next 0.1g, once a day, for at least 3 weeks, and at least 2 weeks after the symptoms are relieved. According to treatment response, the dose can also be increased to 0.4g once a day. (3) Oropharyngeal candidiasis: the first dose is 0.2g, the next 0.1g, once a day, the course of treatment is at least 2 weeks. (4) Candida vulvovaginitis: single dose, 0.15g. (5) Cryptococcal meningitis: 0.4g once, once a day, until the condition improves significantly, then 0.2-0.4g once a day, once a day, at least 10-12 weeks after the cerebrospinal fluid culture becomes negative. Or: 0.4g once, twice a day, for 2 days, then 0.4g once, once a day, the course of treatment is the same as above.
If the patients with renal insufficiency only need to be administered once, there is no need to adjust the dose; when multiple doses are required, the regular dose should be given on the first and second days, and then the dose should be adjusted according to the creatinine clearance rate, as described in the following table :
Creatinine clearance rate (ml/min)
＞ 50 regular dose
11-50 half of the regular dose
Patients undergoing routine dialysis: 1 dose after each dialysis
Pediatric treatment plan has not yet been established. There are data reports that the initial dose is 3-6 mg/kg per day, once a day, to treat a small number of pediatric patients from 2 weeks to 14 years old, and the result is safe.
(1) Common digestive tract reactions, manifested as nausea, vomiting, abdominal pain or diarrhea, etc.
(2) Allergic reaction: It can be manifested as a rash, and occasionally severe exfoliative dermatitis (often accompanied by liver damage), exudative erythema multiforme.
(3) Hepatotoxicity: A mild transient increase in serum aminotransferase may occur during treatment, and symptoms of hepatotoxicity may occasionally occur, especially in patients with serious underlying diseases (such as AIDS and cancer).
(4) Dizziness and headache can be seen.
(5) Some patients, especially those with serious underlying diseases (such as AIDS and cancer), may have abnormal renal function.
(6) Transient neutropenia and thrombocytopenia may occasionally occur in peripheral blood, especially in patients with serious underlying diseases (such as AIDS and cancer).
[Contraindications] People who have a history of allergies to this product or other azole drugs are prohibited.
1. This product can have cross-allergic reactions with other azole drugs, so people who are allergic to any azole drugs should not use this product.
2. Since this product is mainly excreted from the kidney, renal function needs to be checked regularly during treatment. It is used to reduce the dosage of patients with impaired renal function.
3. The current long-term preventive medication of this product in immunodeficiency patients has led to an increase in the resistance of Candida species to fluconazole and other pyrrole antifungal drugs. Therefore, it is necessary to grasp the indications and avoid non-indicated preventive medication.
4. A mild transient increase in serum aminotransferase may occur during treatment, and symptoms of liver toxicity may occasionally occur. Therefore, liver function should be checked regularly before and during treatment with this product. If there is persistent abnormal liver function or clinical symptoms of liver toxicity, this product should be stopped immediately.
5. When this product is used in combination with hepatotoxic drugs, if you need to take this product for more than two weeks or receive multiple times the usual dose of this product, the incidence of hepatotoxicity can be increased. Close observation is required. Every two weeks before and during treatment Liver function tests are performed once a week.
6. The treatment course of this product should be determined according to the infection site and individual treatment response. General treatment should continue until the clinical manifestations of fungal infection and laboratory examination indicators show that the fungal infection disappears. AIDS patients with cryptococcal meningitis or recurrent oropharyngeal candidiasis need to use this product for long-term maintenance treatment to prevent recurrence.
7. For those receiving bone marrow transplantation, if severe neutropenia has occurred in advance, this product should be used prophylactically until the neutrophil count rises to more than 1×109/L for 7 days.
8. For patients with impaired renal function, the dosage can be adjusted according to the aforementioned plan (see [Usage and Dosage]); hemodialysis patients can be given a daily dose of this product after each dialysis, because 3 hours of hemodialysis can make the blood medicine of this product The concentration is reduced by about 50%.
[Medicine for pregnant and lactating women]
1. In animal experiments, when high doses of this product are administered to animals, changes such as miscarriage, increased stillbirths, rib deformities and cleft palate in young animals may occur. Although no such cases have been found in humans, pregnant women should still be contraindicated.
2. There is no data on the concentration of this product in breast milk, so breastfeeding women should use this product with caution or suspend breastfeeding when taking this product.
[Pediatric medication] There is insufficient research data on the effect of this product on children. Although a small number of children from 2 weeks to 14 years old have no adverse reactions at the daily dose of 3-6 mg/kg (by body weight), it is still not suitable for children.
[Medication for the elderly] Elderly patients with no decline in renal function do not need to adjust the dose. Elderly patients with impaired renal function must adjust the dose according to the creatinine clearance rate (see [Usage and Dosage] for details).
(1) When this product is used in combination with isoniazid or rifampicin, the concentration of this product can be reduced.
(2) When this product is used in combination with sulfonylurea hypoglycemic agents such as tolbutamide, chlorbutamide and glipizide, it can increase the blood concentration of such drugs and may cause hypoglycemia, so it is necessary Monitor blood sugar and reduce the dose of sulfonylurea hypoglycemic drugs.
(3) When high doses of this product and cyclosporine are used in combination, the blood concentration of cyclosporine can be increased, and the risk of toxic reactions will increase. Therefore, it is necessary to monitor the blood concentration of cyclosporine and adjust the dose. The following can be applied with caution.
(4) The combination of this product and hydrochlorothiazide can increase the blood concentration of this product.
(5) When this product is used in combination with theophylline, the blood concentration of theophylline can increase by about 13%, which can cause toxic reactions, so the blood concentration of theophylline should be monitored.
(6) When this product is used in combination with warfarin and other dicoumarin anticoagulants, it can enhance the anticoagulant effect of dicoumarin anticoagulants and prolong prothrombin time, so prothrombin time should be monitored And use it with caution.
(7) When this product is combined with phenytoin sodium, it can increase the blood concentration of phenytoin sodium, so the blood concentration of phenytoin sodium should be monitored.
(8) When this product is used in combination with short-acting benzodiazepines such as midazolam, it can cause a significant increase in the blood concentration of midazolam and psychomotor effects. This effect is more obvious in oral administration than intravenous injection. If patients need to receive fluconazole and benzodiazepines at the same time, consider reducing the dose of benzodiazepines and make appropriate observations for the patients.
(9) The combination of this product and cisapride may cause adverse cardiac reactions, including torsade de pointes tachycardia. Cisapride is forbidden for patients receiving fluconazole treatment.
(10) When this product is used in combination with tacrolimus, it can cause the blood concentration of tacrolimus to increase, which may lead to nephrotoxicity. Patients who take fluconazole and tacrolimus should be closely monitored.
(11) When this product is used in combination with terfenadine at a daily dose of 400 mg or higher, it can significantly increase the blood concentration of terfenadine. Combination of fluconazole 400 mg or higher with terfenadine is prohibited. When the daily dose of fluconazole is less than 400 mg and combined with terfenadine, the blood concentration of terfenadine should be closely monitored.
(12) When this product is used in combination with zidovudine, the blood concentration of the latter can be increased. The occurrence of adverse reactions related to zidovudine should be observed.
(13) When this product is combined with astemizole or other drugs metabolized by the cytochrome P-450 system, the serum concentration of these drugs can increase. In the absence of clear information, when combined with fluconazole, these drugs should be used with caution and patients should be closely observed.
Doctors should pay attention to other drug interactions that have not been studied but may occur.
There have been reports of fluconazole overdose. A 42-year-old patient who was infected by the HIV virus experienced hallucinations and excitatory behavior after taking fluconazole 8200 mg. The patient returned to normal within 48 hours after being admitted to the hospital. For patients with overdose, only symptomatic treatment (supportive therapy) can be taken. Most fluconazole is excreted in urine, and forced diuresis may increase its clearance rate. After 3 hours of hemodialysis treatment, the plasma concentration of fluconazole can be reduced by about 50%.
【Pharmacology and Toxicology】
This product is an azole antifungal drug. The antifungal spectrum is wider. Oral and intravenous injection of this product can affect human and various animal fungal infections, such as Candida infection (including systemic candidiasis in people and animals with normal or immunocompromised immunity), cryptococcal infection (including intracranial infection), Malassezia furfur, Microsporum, Trichophyton, Epidermophyton, Blastomyces dermatitis, Coccidioidomycetes (including intracranial infections) and Histoplasma capsulatum, Chromosome Fischerichia, Castellin Mycospore fungus is effective. The antibacterial activity of this product in vitro is significantly lower than that of ketoconazole, but the antibacterial activity of this product in vivo is significantly higher than that of in vitro. 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.
Teratogenic effects: oral administration of fluconazole 20mg/kg to rats can slightly delay the delivery process, but does not affect their fertility. The perinatal results of rats showed that when female rats received 20mg/kg and 40mg/kg, some animals had dystocia and delayed delivery. Mainly manifested as a slight increase in the number of stillbirths and a decrease in the number of surviving newborn rats. The effect of high-dose fluconazole on labor in rats may be related to the specific reduction of estrogen levels in this species of animals.
Mutagenicity: Ames test, mouse lymphoma L5178Y cell line test, animal bone marrow micronucleus test, human lymphocyte chromosome test results are all negative.
Carcinogenicity: The experiment was conducted on mice and rats. Mice and rats were given 2.5, 5, or 10 mg/kg body weight/daily dose (approximately 2-7 times the recommended dose of human body) oral fluconazole 24 Months, suggesting that fluconazole has no carcinogenic effect. However, when male rats received 5 mg/kg and 10 mg/kg of this product for 24 months of continuous administration, the incidence of animal hepatocellular adenomas increased.
[Pharmacokinetics] 100 mg of this product is administered intravenously, and the average peak plasma concentration (Cmax) is 4.5-8 mg/L. The apparent volume of distribution (Vd) is close to the total body fluid. This product has a low plasma protein binding rate (11%-12%), and is widely distributed in the body in tissues and body fluids such as skin, blister fluid, abdominal fluid, sputum, etc. The drug concentration in urine and skin is about 10 times the blood drug concentration ;Blistered skin is about 2 times; saliva, sputum, blister fluid, nails are close to the blood concentration; when meningeal inflammation, the concentration of this product in the cerebrospinal fluid can reach 54%-85% of the blood concentration. A small amount of this product is metabolized in the liver. It is mainly excreted from the kidneys, and more than 80% of the dose is excreted in the urine in its original form. The plasma elimination half-life (t1/2) is 27-37 hours, and it is significantly prolonged when renal function declines.