What Is Butoconazole?

Itraconazole capsules are suitable for the treatment of the following diseases:-Gynecology: vulvovaginal candidiasis. -Dermatology / Ophthalmology:-Tinea versicolor, dermatomycosis, fungal keratitis and oral candidiasis. -Onychomycosis caused by dermatophytes and / or yeast. -Systemic fungal infections: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis) *, histoplasmosis, sporotrichosis, paracoccidiosis, blastomycosis and others A variety of rare systemic or tropical mycosis. * Note: For patients with immunocompromised cryptococcosis and all patients with central nervous system cryptococcosis, this product can only be used when first-line drugs are not applicable or ineffective.

Itraconazole capsules are suitable for the treatment of the following diseases:-Gynecology: vulvovaginal candidiasis. -Dermatology / Ophthalmology:-Tinea versicolor, dermatomycosis, fungal keratitis and oral candidiasis. -Onychomycosis caused by dermatophytes and / or yeast. -Systemic fungal infections: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis) *, histoplasmosis, sporotrichosis, paracoccidiosis, blastomycosis and others A variety of rare systemic or tropical mycosis. * Note: For patients with immunocompromised cryptococcosis and all patients with central nervous system cryptococcosis, this product can only be used when first-line drugs are not applicable or ineffective.

Drug Name

Itraconazole capsules

Drug type

Prescription drugs, medicines for medical workers' injuries

Use classification

Azoles

Itraconazole capsule ingredients

Active ingredient: Itraconazole Chemical name: (±) -cis-4- [4- [4- [4-[[2- (2,4-dichlorophenyl) -2- (1H-1, 2,4-triazole-1-methyl) -1,3-dioxolane-4-yl] methoxy] phenyl] -1-piperazine] phenyl] -2,4-dihydro- Chemical structure of 2- (1-methylpropyl) -3H-1,2,4-triazol-3-one:

Molecular formula: C ₃₅ H ₃₈ Cl ₂ N ₈ O ₄
Molecular weight: 705.64

Itraconazole capsule properties

This product is a powder, blue capsule, and the content is white-like pellets.

Itraconazole capsule specifications

0.1g

Itraconazole capsules dosage

Usage: Oral. For optimal absorption, administer immediately after meals. The capsule should be swallowed whole.
Dosage:
Indication Dose Course Gynaecological Indications 0.2g once or 3 days a day · Candidiasis vulvovaginal 0.2g 2 times a day Illness Dermatology / Ophthalmology Indications tinea versicolor 0.2g once a day 7th skin Fungal disease 0.2g or 0.1g once a day for 7 or 15 days in highly keratinized areas, such as foot tinea and palm tinea, 0.2g twice daily, 7 days or 0.1g once daily, 30 days Day · Oral candidiasis 0.1g once a day for 15 days Some immunodeficiency patients such as leukemia, AIDS or organ transplant patients, the oral bioavailability of itraconazole may be reduced, so the dose can be doubled. Fungal keratitis 0.2 g once a day for 21 days should be adjusted according to the effect of onychomycosis:
-Shock therapy (see the table below): Shock therapy is 0.2 g (2 capsules) twice daily for 1 week. Nail infection requires 2 shock courses, toenail infection is 3 shock courses. Each course was separated by 3 weeks without medication. The obvious curative effect is the development of new nails after the treatment is stopped.
Time / Section Toenail (with or without nail infection) Nail only Week 1 1st shock session 1st shock session 2nd 3rd week Itraconazole is discontinued 4 weeks 5th week 2nd shock course 2nd shock course 6th week 7th Itraconazole is discontinued 8th week 9th 3rd shock course Or-continuous treatment 0.2g (2 capsules) daily for 3 month.
This product clears skin and nail tissues more slowly than plasma. Therefore, for skin infections, the best clinical and mycological effects are achieved 2-4 weeks after stopping the drug, and for onychomycosis, the best clinical and fungal effects are achieved 6-9 months after the drug is stopped.
Systemic mycosis: (select different dosages according to different infections)
Indication dose average course of treatment * Note 0.2g aspergillosis once daily for 2-5 months for patients with invasive or disseminated infection,
Candidiasis 0.1-0.2g once daily for 3 weeks to 7 months Increase the dose to 0.2g twice daily non-meningeal area 0.2g once daily 2 months-1 year maintenance treatment (for meningeal infection)
Cryptococcal disease 0.2g once daily Cryptococcal meningitis 0.2g twice daily 2 months-1 year histoplasmosis 0.2g once daily 2 times 8 months Lymphatic skin type and skin type spores Filariasis 0.1g once a day for 3 months Paracoccidiosis 0.1g once a day for 6 months There is no effective information on the treatment of AIDS patients with this product Coloring fungal disease 0.1-0.2g once a day 6 0.1g once a month for blastomycosis-0.2g twice a day for 6 months * The treatment course should be adjusted according to the curative effect.

Itraconazole capsule adverse reactions

Clinical trials The table below summarizes adverse events reported in the placebo-controlled trials of this product for dermatomycosis and onychomycosis, including all adverse events reported by patients treated with this product at a rate of 1% or more. About 28% and 23% of patients in this product group and placebo group had at least one adverse event. The aggregated adverse events were not related to the investigator's relevance assessment.
The most frequently reported adverse events in gastrointestinal organs were reported in clinical trials.
Table 1: Adverse events with a incidence rate of 1% in this product group

Post-Marketing Experience The spontaneous reported adverse reactions of itraconazole (all dosage forms) after global marketing are listed in Table 2. Adverse reactions are categorized by incidence:
Very common (1 / 10);
Common (1 / 100, and <1/10);
Rare (1 / 1000, and <1/100);
Rare (1 / 10,000 and <1/1000);
Very rare (<1 / 10,000), including individual cases. The spontaneous adverse reaction data reported below cannot accurately assess the incidence in clinical trials and epidemiological studies.

Itraconazole capsules contraindications

-Forbidden in people who are allergic to any of the ingredients of this product.
-Prohibition of use with:
· CYP3A4 metabolic substrates that can cause prolongation of the QT interval, such as: astemizole, benzandil, cisapride, dofetilide, levadone,
Mizolastine, pimozide, quinidine, serindole, terfenadine. When the above drugs are used in combination with this product, the plasma concentrations of these substrates may be increased, leading to a prolonged QT interval and a rare occurrence of apical torsional VT.
-HMG-CoA reductase inhibitors metabolized by CYP3A4, such as lovastatin and simvastatin.
Triazolam and oral midazolam.
Ergot alkaloids, such as dihydroergotamine, ergometrine, ergotamine, and ergometrine.
· Nisoldipine.
-Except for the treatment of life-threatening or severe infections, it is contraindicated in patients with ventricular dysfunction who have or have a history of congestive heart failure (CHF).
-Except for life-threatening cases, it is contraindicated in pregnant women.
-When using this product, women of childbearing age should take appropriate contraceptive measures until the next menstrual cycle after discontinuation.

Precautions for itraconazole capsules

· Heart effects In healthy volunteers using itraconazole injection, a transient, asymptomatic decrease in left ventricular ejection fraction was observed, which disappeared before the next injection.
Itraconazole has shown a negative inotropic effect, which is related to reports of congestive heart failure. The reported spontaneous incidence of heart failure at a daily dose of 400mg is higher than those at lower doses, indicating that the risk of heart failure may increase with the daily dose of this product.
Itraconazole should not be used in patients with congestive heart failure or a history of congestive heart failure unless the benefits outweigh the disadvantages significantly. Factors that should be considered in assessing the pros and cons of an individual include the severity of the condition, the mode of administration (eg, daily dose), and individual risk factors for congestive heart failure.
These risk factors include heart disease, such as ischemic or valvular heart disease; severe lung diseases, such as chronic obstructive pulmonary disease; renal failure and other edema diseases. Physicians should inform such patients about the signs and symptoms of congestive heart failure, use them with caution, and monitor their signs and symptoms of congestive heart failure during treatment. If these signs and symptoms appear during treatment, then itraconazole treatment should be discontinued.
Calcium channel blockers have a negative inotropic effect, thereby enhancing this effect of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers, and the risk of congestive heart failure increases when itraconazole and calcium channel blockers are used in combination.
· Drug Interactions This product has the possibility of drug interactions (see [Drug Interactions]), and these interactions may have clinical significance.
· Decreased gastric acid When the gastric acidity is reduced, the absorption of this product will be affected. Patients receiving acid-neutralizing drugs (such as aluminum hydroxide) should take these drugs at least 2 hours after taking this product. Patients with gastric acid deficiency, such as certain AIDS patients and patients taking acid secretion inhibitors (such as H2 receptor antagonists, proton pump inhibitors), it is best to take this product with cola drinks.
· Effects on the liver When using this product, very rare cases of severe liver toxicity including fatal acute liver failure are very rare. Most of these patients had previously suffered from liver disease, while using this product to treat systemic diseases, they also suffered from some other diseases and / or combined with other drugs with liver toxicity. There are also a few patients who do not have significant risk factors for liver disease. A few of these cases occurred within one month of starting treatment, and individual cases occurred within one week of starting treatment. Patients receiving this product may consider liver function monitoring as appropriate. Patients should be instructed to report to the doctor in a timely manner the signs and symptoms of hepatitis, including loss of appetite, nausea, vomiting, fatigue, abdominal pain or deeper urine. In patients with these symptoms, the drug should be stopped immediately and a liver function test should be performed.
This product should not be used in patients with elevated liver enzymes, active liver disease or other drug-induced liver toxicity, unless the benefits outweigh the risk of liver damage. These cases should be monitored for liver enzymes.
· Liver damage Patients with liver damage have limited data on oral itraconazole, and caution should be used when using this product in such patients.
· Kidney damage Patients with kidney damage have limited data on oral itraconazole, and should be used with caution in such patients.
· Immune-compromised patients For some immunocompromised patients (such as patients with neutropenia, AIDS or organ transplantation), the oral bioavailability of this product may be reduced.
· Patients with life-threatening systemic fungal infections Based on the pharmacokinetic properties of this product, it is not recommended to use this product as the initial treatment for patients with life-threatening systemic fungal infections.
· AIDS patients Doctors who have systemic fungal diseases such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (meninges and non-meningeal areas) and patients who are considered to be at risk of recurrence The need for maintenance treatment should be evaluated.
· Neuropathy should be discontinued when there are neurological symptoms that may be caused by this product.
Hearing loss Patients receiving this product have reported transient or permanent hearing loss. In some of these reports, this product was combined with the contraindicated drug quinidine. Hearing loss usually disappears after treatment is stopped, but it also persists in some patients.
· Cross-allergy There is no information on cross-allergy between itraconazole and other azole antifungals, so patients who are allergic to other azoles should use caution when using itraconazole.
· No influence on the ability to drive and use the machine has been found.
· Keep out of reach of children.

Itraconazole capsules for pregnant and lactating women

-Pregnant women For pregnant women, this product can only be used if the life of the disease is in crisis and the potential benefits outweigh the potential harm to the fetus. Women of childbearing age who use this product should take appropriate contraceptive measures until the next menstrual cycle after the end of treatment.
Animal studies have shown that itraconazole is reproductive.
Information on the use of this product by pregnant women is limited. According to post-marketing experience, there have been cases of congenital malformations, including bone, urogenital, cardiovascular and ocular deformities, as well as chromosomal abnormalities and multiple malformations. The correlation between these cases and this product has not been established.
According to the epidemiological data of the use of itraconazole (mostly short-term treatment of vulvovaginal candidiasis) within three months of pregnancy, compared with the control group without any known teratogenic drugs, this product has not shown Increase deformity.
-Breastfeeding women secrete only a small amount of itraconazole into breast milk. Therefore, lactating women should weigh the pros and cons when using this product, unless its potential benefits outweigh the dangers of breastfeeding when using the drug before using itraconazole. When in doubt, patients should stop breastfeeding.

Itraconazole capsules for children

The clinical data of this product for children is limited. Only when the advantages outweigh the disadvantages can it be used in children.
Or as directed by your doctor.

Itraconazole capsules for the elderly

Due to limited information on the use of this product in the elderly, it can only be used in elderly patients when the advantages outweigh the disadvantages.
Or as directed by your doctor.

Itraconazole capsule drug interactions

1. Drugs that affect itraconazole absorption Drugs that reduce gastric acidity can affect itraconazole absorption.
2. Itraconazole, a drug that affects itraconazole metabolism, is mainly metabolized by CYP3A4. Interaction tests of this product with CYP3A4 strong inducers rifampicin, rifabutin, and phenytoin show that the bioavailability of itraconazole and hydroxyitraconazole will be reduced to a degree sufficient to significantly reduce the efficacy . Therefore, the combination of this product with these strong inducers is not recommended. There are no formal studies on other inducers such as carbamazepine, phenobarbital, and isoniazid, but similar effects are expected.
Inhibitors of CYP3A4 can increase the bioavailability of itraconazole. For example: ritonavir, indinavir, methylerythromycin and erythromycin.
3. The effects of itraconazole on metabolism of other drugs 3.1. Itraconazole inhibits the metabolism of drugs metabolized by the cytochrome 3A family, which can lead to increased and / or prolonged effects, including side effects. When concomitant medications are required, the relevant instructions should be consulted to understand the metabolic pathways of the drug. After discontinuing treatment with this product, the plasma itraconazole concentration gradually decreases, and the rate of decrease depends on the dose and time (see [Pharmacokinetics]). When considering the inhibitory effect of itraconazole on combined drugs This feature should be considered.
Examples are as follows:
Medications that should not be used during treatment with this product:
Astemizole, benpridil, cisapride, dofetilide, levofetab (methotone), mizolastine, pimozide, quinidine serindole, terfenadine. When the above drugs are used in combination with this product, it may cause the plasma concentration of these substrates to increase, leading to the prolongation of QT interval and the rare occurrence of apical torsional VT.
HMG-CoA reductase inhibitors metabolized by CYP3A4, such as lovastatin or simvastatin.
Triazolam and oral midazolam.
Ergot alkaloids, such as dihydroergotamine, ergometrine, ergotamine, and ergometrine.
Nisoldipine.
· Itraconazole can inhibit the metabolism of calcium channel blockers. When itraconazole and calcium channel blockers are used in combination, the risk of congestive heart failure increases, which requires attention. In addition to possible pharmacokinetic interactions related to the drug metabolism enzyme CYP3A4, calcium channel blockers also have a negative inotropic effect, thereby enhancing this potential effect of itraconazole.
· Drugs that require monitoring of plasma concentrations, drug effects, and side effects during treatment with this product should be reduced when necessary in combination with itraconazole.
Oral anticoagulants.
Anti-HIV protease inhibitors, such as ritonavir, indinavir, and saquinavir.
Certain anti-tumor drugs, such as vinca alkaloids, busulfan, docetaxel, and trimethyltrifloxacin.
Calcium channel blockers metabolized by CYP3A4, such as dihydropyridine and verapamil.
Certain immunosuppressants, such as cyclosporin, tacrolimus, rapamycin.
Certain HMG-CoA reductase inhibitors metabolized by CYP3A4, such as atorvastatin.
Certain glucocorticoids, such as budesonide, dexamethasone, fluticasone, methylprednisolone.
Digoxin (by inhibiting P-glycoprotein).
Others: Alfentanil, Alprazolam, Brotizolam, Buspirone, Carbamazepine, Cilostazol, Diisopyramine, Ebastine, Elitoran, Fentanyl , Halofen, intravenous midazolam, reboxetine, riglitinide, rifabutin.
3.2. The interaction of itraconazole with zidovudine and fluvastatin has not been observed. No induction effect of itraconazole on ethinylestradiol and norethisterone metabolism has been observed.
4. Effect on protein binding In vitro tests have shown that in terms of protein binding, itraconazole and imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethoxine No interaction between them.

Itraconazole capsules overdose

When overdose occurs, supportive care should be taken. Gastric lavage can be taken within 1 hour after ingestion. If necessary, activated charcoal can be given.
This product cannot be removed by hemodialysis.
No special antidote.

Itraconazole capsules pharmacology and toxicology

Pharmacological effects-Pharmacological classification: J02A C02 (systemic antifungal, triazole derivatives).
-Itraconazole is a triazole derivative with broad-spectrum antifungal activity.
-In vitro tests have shown that itraconazole can inhibit the growth of a variety of human pathogenic fungi in the normal concentration range (0.025g / ml to 0.8g / ml), including:
Dermatophytes (Trichophyton, Microsporum, Epidermophyton), yeasts (Candida include Candida albicans, Candida glabrata and Candida krusei; Cryptococcus neoformans; Malasse Trichoderma spp .; Trichospodium spp., Aspergillus spp., Histoplasma spp., Paracoccus brasiliensis, Mycosporium schenckii, Pythium sp Alisma, Penicillium manefei, and many other yeasts and fungi.
Candida crocus, Candida glabrata and Candida tropicalis are usually the least sensitive Candida strains. In in vitro tests, individual tests have shown significant resistance to itraconazole.
-Fungi that are not inhibited by itraconazole are Zygomycetes (Rhizobium, Rhizomucor, Mucor, and Phytophthora), Fusarium, Saidiospore, and Broommyces.
-The results of in vitro tests indicate that itraconazole can disrupt ergosterol synthesis in fungal cell membranes. Ergosterol is an important part of the fungal cell membrane, and interference with its synthesis will eventually produce antifungal effects.
Toxicological studies The preclinical safety of itraconazole has been confirmed by a series of standardized studies.
Acute toxicity studies in mice, rats, guinea pigs, and dogs have shown that itraconazole has a wide range of safety. Sub-long-term oral toxicity studies in rats and dogs revealed the presence of some target organs or tissues (adrenal cortex, liver, and monocyte phagocytic system), and fatty metabolic diseases manifested as yellow tumors in others .
At high doses, histological studies of the adrenal cortex revealed reversible swellings in the reticular and bundle areas with cell hypertrophy, sometimes accompanied by thinning of the bulbous area. At high doses, reversible liver changes were also observed: vacuole-like changes in sinusoidal and hepatocytes, the latter changes suggesting cell dysfunction but no hepatitis or hepatocyte necrosis. The histological changes of the monocyte phagocytic system are mainly the increase of protein-like substances of macrophages in interstitial tissues.
Itraconazole did not show mutagenicity.
Studies in rats and mice have shown that itraconazole is not a primary carcinogen. However, a higher incidence of soft tissue tumors was observed in male rats due to non-neoplastic chronic inflammatory reactions in connective tissue, which resulted in increased cholesterol levels and cholesterol accumulation in connective tissue.
There is no evidence that treatment with itraconazole has a primary effect on fertility. In high-dose studies on rats and mice, dose-related maternal toxicity, embryo toxicity, and teratogenicity were observed. Malformations in rats include major bone defects, and malformations in mice include encephalocele and macrotongue.
In puppies administered chronically, a decrease in bone density was observed.
In three toxicological studies in rats, itraconazole can cause skeletal defects, including reduced bone plate activity, thinning of large bone dense areas, and increased bone fragility.

Pharmacokinetics of itraconazole capsules

· General pharmacokinetic properties Single and multiple doses were administered to healthy subjects, special populations and patients to study the pharmacokinetic properties of itraconazole. In general, itraconazole is well absorbed, reaching peak plasma concentrations within 2-5 hours after oral administration. Itraconazole is mainly metabolized in the liver, producing a variety of metabolites. The main metabolite is hydroxyitraconazole, whose plasma concentration is twice that of the original drug. The half-life of itraconazole in a single dose is about 17 hours, and the half-life of repeated doses is increased to 34-42 hours. Itraconazole's pharmacokinetics are not linear, so drug accumulation in plasma can occur after repeated administration. Steady state can be achieved within 15 days after oral administration, with peak blood concentrations of 0.5 g / ml (once a day, 100 mg once), 1.1 g / ml (once a day, 200 mg once), and 2.0 g / ml ( 200mg twice a day). After the treatment was stopped, the plasma concentration of itraconazole dropped to almost undetectable within 7 days. Due to the saturation mechanism of liver metabolism, itraconazole clearance can decrease with increasing dose. Itraconazole is excreted as inactive metabolites through urine (about 35%) and feces (about 54%).
· Absorbed quickly after oral itraconazole absorption. After a single dose of oral itraconazole, peak plasma concentrations were reached within 2-5 hours. The observed absolute bioavailability of itraconazole is approximately 55%. Medication was taken immediately after a meal, and oral bioavailability was highest.
· Itraconazole distribution has a high plasma protein binding rate (99.8%), mainly binding to albumin, and the protein binding rate of hydroxyl metabolites is 99.6%. Itraconazole has a high affinity for lipids, and only 0.2% of itraconazole in plasma exists in free form. Itraconazole has a high apparent distribution volume (700L), indicating that it has a wide tissue distribution, and the drug concentration in the lung, kidney, liver, bone, stomach, spleen, and muscle is 2-3 higher than the corresponding plasma drug concentration The drug concentration in the stratum corneum and skin is 4 times higher than the corresponding plasma drug concentration, and the drug concentration in the brain is comparable to the plasma drug concentration.
· Metabolism Itraconazole is mainly metabolized into various metabolites in the liver. The main metabolite is hydroxyitraconazole, which shows antifungal activity comparable to that of itraconazole in in vitro tests. Its plasma concentration is twice that of the original drug.
In vitro experiments show that CYP3A4 is the main enzyme involved in itraconazole metabolism.
· Within a week of excretion, itraconazole is excreted as inactive metabolites through urine (about 35%) and feces (about 54%). Prototype drugs are excreted through the kidneys at a rate of less than 0.03% and excreted in the feces at approximately 3-18%.
The redistribution of itraconazole from keratinized tissue is negligible, so elimination of itraconazole from these tissues is associated with epidermal regeneration. After the treatment for 4 consecutive weeks, the concentration of the drug in the skin can be different from the plasma concentration for 2-4 weeks. The drug concentration in the keratin can be measured as early as 1 week after the start of the medication, and can last for 6 months after the end of the 3 month course of treatment.
Itraconazole is metabolized in the liver in the special population. Twelve patients with liver cirrhosis and six healthy volunteers received a single dose of 100 mg itraconazole capsules. The Cmax, AUC and half-life of itraconazole were compared between the two groups. The average Cmax in patients with cirrhosis was significantly decreased (47%), and the mean elimination half-life was longer than that in patients with normal liver function (37 and 16 hours, respectively). According to the AUC value, the total exposures of patients with liver cirrhosis and healthy volunteers were similar. There are no data on long-term use of itraconazole in patients with cirrhosis.
Renal Impairment Data on oral itraconazole in patients with renal impairment are limited. Patients with renal impairment should use caution when using this product.

Itraconazole capsule storage

Sealed and stored in a cool, dry place.

Itraconazole capsules

Packed in aluminum-plastic board. 4 tablets / board / box, 2 × 7 tablets / board / box.

Itraconazole capsule expiration date

24 months

Itraconazole capsules

"Chinese Pharmacopoeia" 2010 edition two ^[1]