What Is Miconazole?

Miconazole is a highly effective, safe, and broad-spectrum antifungal drug, which has almost all effects on pathogenic fungi. The mechanism is to inhibit the sterol synthesis of the fungal cell membrane, affect the cell membrane permeability, inhibit fungal growth, and cause death. At concentrations below 4 µg / mL, most clinically isolated fungi can be inhibited. Among them, new cryptococcus, candida and crude spores are sensitive to this product. Bacterial dermatitis and histoplasma are highly sensitive to this product. Poor mold. In addition, miconazole also has antibacterial effects on Staphylococcus aureus and Streptococcus and Gram-positive cocci and anthrax. For skin fungal infections, such as hand, foot, body, jock itch.

Drug Name: Miconazole
Alias: Diclofenazole, mycoconazole, MONISTAT
Foreign name: Miconazole

Whether prescription drugs: Non-prescription drugs
Main indications: For skin fungal infections
Dosage: 600mg 1 800mg / day, divided into 3 times
Adverse reactions: Rash, redness, blisters, etc.

Introduction to miconazole compounds

Miconazole Basic Information

Chinese name MICONazole

Chinese alias: dichlorobenzimidazole; 1- [2- (2,4-dichlorophenyl) -2-[(2,4-dichlorophenyl) methoxy] ethyl] -1H-imidazole; Benconazole; mycoconazole; mycoconazole; miconazole; cloconazole; mycogram; daconin; daconin: enzyme conazole; enzyme coconazole; enzyme coconazole; Miconazole

English name: Miconazole

English alias: MONISTAT IV; mjr1762; Daktarin IV; 1- [2- (2,4-Dichlorophenyl) -2-[(2,4-dichlorophenyl) methoxy] ethyl] -1H-imidazole; micronazol; brentan; daktar; daktarin Dermarin florid gyno-daktar micatin micotef monistat derm miconazolum

CAS number: 22916-47-8

Molecular formula: C ₁₈ H ₁₄ Cl ₄ N ₂ O

Molecular Structure:

Molecular weight: 416.12900

Exact mass: 413.98600

PSA: 27.05000

LogP: 6.45480

Physicochemical properties of miconazole

Appearance and properties: white powder, odorless or almost odorless. Soluble in ethanol, chloroform and methanol, insoluble in water and ether.

Density: 1.4g / cm ³

Melting point: 159-163ºC

Boiling point: 555.1ºC at 760mmHg

Flash point: 289.5ºC

Refractive index: 1.639

Stability: Stable, stored in a closed container at room temperature.

Storage conditions: Store in a closed container. Store in a cool, dry, well-ventilated area away from incompatible materials.

Vapor pressure: 6.07E-13mmHg at 25 ° C

Miconazole safety information

Packing level: III

Hazard category: 6.1 (b)

Customs Code: 2933290090

Dangerous Goods Transport Code: UN 3249

Danger category code: R22

Safety instructions: S22; S36 ^[1]

Miconazole production method

Manufactured from 2,2 ', 4'-trichloroacetophenone ^[1] .

Miconazole uses

It belongs to imidazole broad-spectrum antimycotics. It has good antibacterial activity against Cryptococcus neoformans, Candida, Coccidioides, histoplasma and dermatitis. It is effective on Trichophyton and Dermatophyte, but it has a poor effect on molds and some white cocci. ^[1] .

Miconazole history

In 1969, Godefroi was synthesized, and then developed and produced by the Belgian company Jassan. In 1984, Shanghai No. 2 Pharmaceutical Factory was put into production. Place of origin is Shanghai and Jiangsu, Zhejiang, Guangdong and other provinces. Methyl-dichlorobenzene is acylated, reduced, and then condensed with imidazole to obtain 2- (2,4-dichlorophenyl) -imidazole-1-ethanol, and then condensed with 2,4-dichlorochlorobenzyl. Pharmacopoeia in China, the United Kingdom, the United States, France, Germany, Switzerland and other countries are contained.

Miconazole drug description

Miconazole specifications

Injection: 10mg / ml; cream, lotion: 2% miconazole nitrate; vaginal suppository: 100mg / suppository.

Miconazole indications

Dermatophytes, yeast Candida, etc. on the skin. Nail infections, such as tinea capitis, tinea pedis, athlete's foot, ringworm, jock itch, tinea versicolor, paronychia; vaginal or penis glans fungal infections; aspergillus or other fungal infections. The cream is widely used to treat vaginal fungal infections, such as candidal vaginitis, with a cure rate of about 90%. It can still be used after switching to patients who have not used one or more other antifungals. Effective and treatment time is shorter. Topical application of this product is also effective for fungal infections of erosive or smooth skin. The diluted solution (0.2% 0.5%) of this product can be safely used for washing fungi in the bladder, trachea and wounds.

Pharmacological effects of miconazole

Miconazole is a synthetic 1-phenethylimidazole derivative. It is a broad-spectrum antifungal drug. It can inhibit and kill dermatophytes, candida, yeast and other algae, ascomycetes, cryptococcus, etc. Also resistant to Gram-positive cocci and bacilli

Miconazole ointment Bacterial effect. Broad-spectrum antifungal. The product can inhibit the growth of most fungi at a concentration of 4mg / L, and the genus Bacteroides and Histoplasma are highly sensitive to it. Cryptococcus, Candida, and Coccus are also sensitive to this product. This product inhibits the biosynthesis of sterols, the major sterols in fungal cell membranes, by interfering with the activity of cytochrome P-450, damages the fungal cell membrane and changes its permeability, leading to the leakage of important intracellular materials; It can inhibit the biosynthesis of triacylglycerol and phospholipid of fungi, inhibit the activity of oxidase and peroxidase, cause the accumulation of intracellular hydrogen peroxide, and cause cell submicrostructure degeneration and cell necrosis. Candida albicans can inhibit its transformation from spores to invasive hyphae. The content of this product is white or almost white crystalline powder; odorless or almost odorless.

Miconazole pharmacokinetics

Literature data show that oral absorption of miconazole is poor. The peak plasma concentration is only 1 mg / L after oral administration of 1 g, the distribution half-life is about 0.4 hours, the elimination half-life is about 2.1 hours, and the terminal half-life is 20 to 24 hours. Serum protein binding The rate is 90%. It is widely distributed in the body and can penetrate into the inflammatory joints, the vitreous body of the eyeballs, and the abdominal cavity, but the concentrations in the cerebrospinal fluid, sputum, and aqueous humor are very low, and the permeability to the blood-brain barrier is also poor. This product is mainly metabolized by the liver to inactive metabolites. 14 to 22% of the oral amount is excreted from the urine, mainly inactive metabolites, of which less than 1% is the original. 50% of the oral dose is excreted from the feces in its original form. There is currently no data on the pharmacokinetics of the product for topical application to the skin.

Miconazole adverse reactions

Rash, redness, blisters, burning sensation and other skin irritation symptoms. Phlebitis, itching, fever, rash. Can cause gastrointestinal reactions: nausea, vomiting, loss of appetite, bloating, diarrhea. Hematocrit decreased, leukopenia, hyponatremia.

[Cardiovascular system] A single assault amount (800mg, injection completed in 1 to 2 minutes) caused some patients to develop tachycardia and rapid breathing. One patient developed ventricular tachycardia and the other suffered cardiac arrest. The incidence of thrombophlebitis is higher during intravenous injection, which can be prevented by central venous catheter injection. Despite improving the buffer, its incidence is still 20%. Seven patients with malignant blood quality disorders were reported to be treated with this drug. Two patients had cardiac arrest, four had allergic reactions, and one had respiratory arrest. All of these occurred at the time of the first medication, and 7 patients recovered after discontinuation. None of them had a history of heart disease. Five of them used a higher concentration of the solution (dissolved in less than 200ml of liquid). Therefore, the drug should be dissolved in more than 200ml of liquid and the input time should be no less than 60 minutes. Can avoid complications.

[Nervous system] Intrathecal injection can cause arachnoiditis. May cause hypersensitivity, euphoria, and dizziness, but rare and mild. Rare toxic psychosis.

[Digestive system] Nausea, vomiting, diarrhea, and loss of appetite can occur, which can occur both orally and intravenously. For example, in 80 patients, the incidence of nausea can reach 42%. No toxic effect on the liver has been seen, but occasionally mild transient elevations in serum aminotransferases have occurred.

[Hematopoietic system] Occasionally, normal red blood cell anemia or leukocytes and thrombocytopenia may occur. The incidence of the latter two is less than 2%, and they can quickly return to normal after stopping the drug. About 2% of patients may develop hyperlipidemia and a red blood cell arrangement, and both blood cholesterol and triglyceride may increase, which may be related to castor oil excipients used in intravenous preparations. A few patients can develop hyponatremia.

[Allergic reactions] A small number of patients may develop allergic reactions such as skin itching, rash, dizziness, cold and fever, and occasional anaphylactic shock. Macular pimples have been reported, sometimes with or without urticaria. Some patients continue to take the medication, and the rash can go away naturally. Local application of this product will cause local skin irritation and contact allergic dermatitis. 1. Gastrointestinal reactions such as nausea, vomiting, diarrhea, and loss of appetite; 2. A small number of patients may develop itching, rash, dizziness, cold, fever, etc., and occasionally anaphylactic shock; 3. Occasionally, normal red blood cell anemia may occur , Granulocyte and thrombocytopenia, hyperlipidemia (such as elevated cholesterol and triacylglycerol). Occasionally can cause a transient mild increase in serum aminotransferase.

Miconazole side effects

1 Phlebitis. 2 Allergic reactions, rash, itching of the skin. 3 Gastrointestinal reaction, nausea and vomiting. 4 Be wary of liver toxicity. Discontinue treatment if symptoms of liver damage occur. 5 Children under 1 year old do not use this product. Disable pregnant women.

Topical application can cause rashes, redness, blisters, burning sensations, and other skin irritation. Avoid contact with eyes. A lotion should be used on the friction parts. If a small amount of cream is applied, it should be rubbed evenly to avoid soaking. Encapsulation should be avoided in the treatment of candidiasis, so as not to promote yeast growth and release of endotoxin. Candida infection, jock itch and body ringworm should be treated for 2 to 4 weeks, tinea pedis for 1 month, and onychomycosis for 6 months.

Relevant foreign reports, application of the product in the vulva and vagina, 100 mg a day for 7 consecutive days, 6% to 7% of patients with burning, itching or irritation; only 0.9% of patients discontinued treatment. Another report reported that 200 mg of the product was inserted into the vagina every night for 3 consecutive days, and 2% of patients experienced burning, itching, and irritation, 0.5% of patients developed a rash, and 0.3% of patients discontinued treatment.

Miconazole usage dosage

external use. For ringworm, jock itch and tinea pedis, aerosol sprays, aerosol solutions, creams,

Miconazole ointment Lotions and spreads, one morning and one evening, continuous medication for at least 4 weeks. For skin candidiasis, creams should be used once in the morning and evening. Tinea versicolor should be used cream once a day. If the skin has an erosive surface, the lotion should be applied first (without cream), twice a day for 2 weeks. For vaginal or vulvar, glans infection, apply cream or suppository, once a night, 3 to 5 grams of cream or 1 suppository, apply or stuff into the vagina for 7 to 14 consecutive days. For onychomycosis, apply cream, one morning and one evening, for six months in a row.

Miconazole precautions

1. Be sure to dilute the injection before intravenous drip. Can cause cardiac arrest, medication should be closely observed.

2. Occasionally can cause allergic reactions, and must be administered under strict observation in hospital.

3. Phlebitis is a common side effect, and itching, nausea, fever and chills, dizziness, rash, and vomiting are common. Patients with severe itching and rash should discontinue medication. Nausea and vomiting can be anti-histamines or antiemetics, and avoid the administration before and after meals, can also reduce the dosage appropriately.

4. It can cause decreased hematocrit, thrombocytopenia, and decreased blood sodium. During the medication, hemoglobin, hematocrit, electrolytes and blood lipids should be checked, and any abnormalities should be handled in time.

5. Children under one year old do not need this product. Disabled during pregnancy.

6, can not be compatible with some complex infusion.

Medication for pregnant and lactating women

Animal tests have shown that miconazole is toxic to the fetus, so pregnant women have banned this product; it is not clear whether this product will be secreted into milk, so it is not recommended for lactating women.

Medication for children Because children are in the growth and development stage and liver function is not yet perfect, the amount of medication should be reduced.

Medication for Elderly Patients For elderly patients with reduced liver function, the dosage should be reduced.

Miconazole drug interactions

1. When this product is combined with anticoagulants such as coumarin or indanedione derivatives, it can enhance this

Miconazole ointment The effects of the drugs caused prolonged prothrombin time. Patients should be closely observed, the prothrombin time should be monitored, and the dose of anticoagulants should be adjusted.

2. This product can increase the blood concentration of cyclosporine and may increase the risk of nephrotoxicity. When the two drugs are combined, the blood concentration of cyclosporine should be monitored. 3. Rifampicin can enhance the metabolism of the product, increase liver toxicity, and reduce the blood concentration of the product when used in combination, leading to treatment failure. It can also reduce the blood concentration of this product when combined with isoniazid, so the above drugs should be used with caution.

4. The combined use of phenytoin and this product can cause changes in the metabolism of the two drugs, and delay the peak time of the product. The reaction should be closely observed when the two drugs are used in combination.

5. When this product is used in combination with a hypoglycemic agent, it can cause severe hypoglycemia due to inhibition of the latter's metabolism.

6. This product is contraindicated with cisapride, because it inhibits the cytochrome P-450 metabolic channel when used in combination, which can lead to cardiac rhythm disturbance. This product is also at risk of arrhythmia if it is used in combination with astemizole or terfenadine, so it should also be avoided.

Miconazole marketed preparations

Daconin suppositories: suppositories, manufactured by Xi'an Janssen Pharmaceutical Co., Ltd. 200 mg each, for external use, for vaginal candidiasis infection, one at a time, stuffed into the vagina before going to bed for 7 to 14 consecutive days.

Daconin cream: cream, produced by Xi'an Janssen Pharmaceutical Co., Ltd. 15 g, 40 g each, containing 300 mg and 800 mg of miconazole, for external use, for superficial fungal infections of the skin, candidiasis of the skin, finger (toe), angular cheilitis and external otitis, coated Apply the affected area 1 to 2 times a day, apply skin infection for 10 consecutive days, nail infection for six months, and vaginal infection for 14 days. Store in a closed, shady place for a period of 5 years.

Miconazole capsule preparation

Miconazole nitrate capsules

English name

MiconazoleNitrateCapsules

category

Western medicine

Pharmacological action

Broad-spectrum antifungal. This product can inhibit the growth of most fungi at the concentration of 4mg / L.

Miconazole capsules It is highly sensitive to it, and Cryptococcus, Candida, and Coccus are also sensitive to it. This product inhibits the biosynthesis of sterols, the major sterols in fungal cell membranes, by interfering with the activity of cytochrome P-450, damages the fungal cell membrane and changes its permeability, leading to the leakage of important intracellular materials; It can inhibit the biosynthesis of triacylglycerol and phospholipid of fungi, inhibit the activity of oxidase and peroxidase, cause the accumulation of intracellular hydrogen peroxide, and cause cell submicrostructure degeneration and cell death. Candida albicans can inhibit its transformation from spores to invasive hyphae. The content of this product is white or almost white crystalline powder; odorless or almost odorless.

Pharmacokinetics

The oral absorption of this product is poor, and the peak blood concentration after oral administration is only 1mg / L. The blood distribution half-life (t1 / 2) is about 0.4 hours, the blood elimination half-life (t1 / 2) is about 2.1 hours, the terminal half-life (t1 / 2) is 20-24 hours, and the serum protein binding rate is 90%. It is widely distributed in the body and can penetrate into the inflammatory joints, the vitreous body of the eyeballs, and the abdominal cavity, but the concentrations in the cerebrospinal fluid, sputum, and aqueous humor are very low, and the permeability to the blood-brain barrier is also poor. This product is mainly metabolized by the liver to inactive metabolites. 14% to 22% of the oral amount is excreted from the urine, mainly inactive metabolites, of which less than 1% is the original. 50% of the oral dose is excreted from the feces in its original form.

Indication

This product is mainly used to treat intestinal candida infection.

Dosage

Orally after meals. Adults are 0.25 to 0.5 g once and 0.5 to 1 g per day. The initial oral dose for children is 30 to 60 mg / kg daily, and then reduced to 10 to 20 mg / kg daily. For infants, 30 mg / kg daily is divided into two doses. The course of treatment depends on the condition.

Adverse reactions

1, gastrointestinal reactions such as nausea, vomiting, diarrhea and loss of appetite;

2. A small number of patients may have itching, rash, dizziness, cold, fever, etc., and occasionally anaphylactic shock;

3. Occasionally, normal red blood cell anemia, granulocyte and thrombocytopenia, and hyperlipidemia (such as elevated cholesterol and triacylglycerol) may occur. Occasionally can cause a transient mild increase in serum aminotransferase.

Taboo

Infants under one year old, pregnant women, patients with liver dysfunction and those who are allergic to this product are prohibited.

Precautions

Periodically check the surrounding blood, blood cholesterol, triacylglycerol and serum aminotransferase during treatment. Due to the child's growth and development, liver function is not yet perfect, the dosage should be reduced. Animal tests have shown that miconazole is toxic to the fetus, so pregnant women have banned this product; it is not clear whether this product will be secreted into milk, so it is not recommended for lactating women. For elderly patients with reduced liver function, the dose should be reduced.

medicine interactions

1. When combined with anticoagulants such as coumarin or indanedione derivatives, this product can enhance the effect of such drugs, leading to prolonged prothrombin time. Patients should be closely observed, monitored for prothrombin time, adjusted Anticoagulant dosage.

3. Rifampicin can enhance the metabolism of the product, increase liver toxicity, and reduce the blood concentration of the product when used in combination, leading to treatment failure. It can also reduce the blood concentration of this product when combined with isoniazid, so the above drugs should be used with caution.

5. When this product is used in combination with a hypoglycemic agent, it can cause severe hypoglycemia due to inhibition of the latter's metabolism.

6. This product is contraindicated in combination with cisapride, because it inhibits the cytochrome P-450 metabolic channel when used in combination, which can lead to heart rhythm disorders. This product is also at risk of arrhythmia if used in combination with astemizole or terfenadine, so it should also be avoided ^[2] .

preparation

0.25g