Dosage of Micotrazol in details
Use only the components [Micotrazol® (Micotrazol) Injection ampule, 0.9% Sodium Chloride Injection, USP (Normal Saline) bag and filtered infusion set] provided in the kit: DO NOT SUBSTITUTE.
Micotrazol® (Micotrazol injection) Injection should not be diluted with 5% Dextrose Injection, USP, or with Lactated Ringer's Injection, USP, alone or in combination with any other diluent. The compatibility of Micotrazol® (Micotrazol injection) Injection with diluents other than 0.9% Sodium Chloride Injection, USP (Normal Saline) is not known. NOT FOR IV BOLUS INJECTION.
NOTE: After reconstitution, the diluted Micotrazol® (Micotrazol injection) Injection may be stored refrigerated (2-8°C) or at room temperature (15-25°C) for up to 48 hours, when protected from direct light. During administration, exposure to normal room light is acceptable.
NOTE: Use only a dedicated infusion line for administration of Micotrazol® (Micotrazol injection) Injection. Do not introduce concomitant medication in the same bag nor through the same line as Micotrazol® (Micotrazol injection) Injection. Other medications may be administered after flushing the line/catheter with 0.9% Sodium Chloride Injection, USP, as described below, and removing and replacing the entire infusion line. Alternatively, utilize another lumen, in the case of a multi-lumen catheter.
Correct preparation and administration of Micotrazol® (Micotrazol injection) Injection are necessary to ensure maximal efficacy and safety. A precise mixing ratio is required in order to obtain a stable admixture. It is critical to maintain a 3.33 mg/mL Micotrazol:diluent ratio. Failure to maintain this concentration will lead to the formation of a precipitate.
Add the full contents (25 mL) of the Micotrazol® (Micotrazol injection) Injection ampule into the infusion bag provided, which contains 50 mL of 0.9% Sodium Chloride Injection, USP (Normal Saline). Mix gently after the solution is completely transferred. Withdraw and discard 15 mL of the solution before administering to the patient. Using a flow control device, infuse 60 mL of the dilute solution (3.33 mg/mL = 200 mg Micotrazol, pH apx. 4.8) intravenously over 60 minutes, using an extension line and the infusion set provided. After administration, flush the infusion set with 15-20 mL of 0.9% Sodium Chloride Injection, USP, over 30 seconds-15 minutes, via the two-way stopcock. Do not use Bacteriostatic Sodium Chloride Injection, USP. The compatibility of Micotrazol® (Micotrazol injection) Injection with flush solutions other than 0.9% Sodium Chloride Injection, USP (Normal Saline) is not known. Discard the entire infusion line.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Empiric Therapy in Febrile, Neutropenic Patients with Suspected Fungal Infections (ETFN)
The recommended dose of Micotrazol® (Micotrazol injection) Injection is 200 mg b.i.d. for four doses, followed by 200 mg once daily for up to 14 days. Each intravenous dose should be infused over 1 hour. Treatment should be continued with Micotrazol® (Micotrazol injection)
Oral Solution 200 mg (20 mL) b.i.d. until resolution of clinically significant neutropenia.
The safety and efficacy of Micotrazol® (Micotrazol injection) use exceeding 28 days in ETFN is not known.
Treatment of Blastomycosis, Histoplasmosis and Aspergillosis
The recommended intravenous dose is 200 mg b.i.d. for four doses, followed by 200 mg q.d. Each intravenous dose should be infused over 1 hour.
For the treatment of blastomycosis, histoplasmosis and aspergillosis, Micotrazol® (Micotrazol injection) can be given as oral capsules or intravenously. The safety and efficacy of
Micotrazol® (Micotrazol injection) Injection administered for greater than 14 days is not known.
Total Micotrazol therapy (Micotrazol® (Micotrazol injection) Injection followed by Micotrazol® (Micotrazol injection) Capsules) should be continued for a minimum of 3 months and until clinical parameters and laboratory tests indicate that the active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection.
Use in Patients with Renal Impairment
Limited data are available on the use of intravenous Micotrazol in patients with renal impairment.
Hydroxypropyl-β-cyclodextrin, a required component of SPORANOXintravenous formulation, is eliminated through glomerular filtration. Therefore, in patients with severe renal impairment (defined as creatinine clearance below 30 mL/min), the use of Micotrazol® IV is contraindicated.
In patients with mild (defined as creatinine clearance 50-80 mL/min) and moderate (defined as creatinine clearance 30-49 mL/min) renal impairment, Micotrazol® (Micotrazol injection) Injection should be used with caution. Serum creatinine levels should be closely monitored and, if renal toxicity is suspected, consideration should be given to modifying the antifungal regimen to an alternate medication with similar antimycotic coverage.
Use in Patients with Hepatic Impairment
Limited data are available on the use of Micotrazol in patients with hepatic impairment. Caution should be exercised when this drug is administered in this patient population..
How supplied
Micotrazol® (Micotrazol) Injection for intravenous infusion is supplied as a kit (NDC 50458-298-01), containing one 25 mL colorless glass ampule of Micotrazol 10 mg/mL sterile, pyrogen-free solution (NDC 50458-297-10), one 50 mL bag (100 mL capacity) of 0.9% Sodium Chloride Injection, USP (Normal Saline) and one filtered infusion set.
Store at or below 25°C (77°F). Protect from light and freezing.
Keep out of reach of children.
Manufactured for: Ortho Biotech Products, L.P Raritan, NJ 08869. Manufactured by: Hospira, Inc. Lake Forest, IL 60045. Revised March 2009.
What other drugs will affect Micotrazol?
Many drugs can interact with Micotrazol, and some drugs should not be used together. Tell your doctor about all your medicines and any you start or stop using during treatment with Micotrazol, especially:
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antipsychotic medicine or a sedative (such Valium or Xanax);
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HIV/AIDS medicine;
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medicine to treat high cholesterol;
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an antibiotic - ciprofloxacin, clarithromycin, erythromycin;
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a blood thinner - rivaroxaban, warfarin, Coumadin, Jantoven;
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cancer medicine - dasatinib, nilotinib, and others;
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drugs to treat urinary problems - Detrol, Flomax, Vesicare;
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heart or blood pressure medication - aliskiren, digoxin, diltiazem, verapamil, and others;
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immunosuppressants - dexamethasone, everolimus, and others;
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medicine to prevent organ transplant rejection - cyclosporine, sirolimus, and others;
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migraine headache medicine - eletriptan and others;
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narcotic pain medicine - fentanyl, oxycodone, and others; or
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seizure medicine - carbamazepine and others.
This list is not complete and many other drugs can interact with Micotrazol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Give a list of all your medicines to any healthcare provider who treats you.
Micotrazol interactions
Micotrazol and its major metabolite, hydroxyitraconazole, are inhibitors of CYP3A4. Therefore, the following drug interactions may occur :
- Micotrazol® (Micotrazol injection) may decrease the elimination of drugs metabolized by CYP3A4, resulting in increased plasma concentrations of these drugs when they are administered with Micotrazol® (Micotrazol injection). These elevated plasma concentrations may increase or prolong both therapeutic and adverse effects of these drugs. Whenever possible, plasma concentrations of these drugs should be monitored, and dosage adjustments made after concomitant Micotrazol® (Micotrazol injection) therapy is initiated. When appropriate, clinical monitoring for signs or symptoms of increased or prolonged pharmacologic effects is advised. Upon discontinuation, depending on the dose and duration of treatment, Micotrazol plasma concentrations decline gradually (especially in patients with hepatic cirrhosis or in those receiving CYP3A4 inhibitors). This is particularly important when initiating therapy with drugs whose metabolism is affected by Micotrazol.
- Inducers of CYP3A4 may decrease the plasma concentrations of Micotrazol. Micotrazol® (Micotrazol injection) may not be effective in patients concomitantly taking Micotrazol® (Micotrazol injection) and one of these drugs. Therefore, administration of these drugs with Micotrazol® (Micotrazol injection) is not recommended.
- Other inhibitors of CYP3A4 may increase the plasma concentrations of Micotrazol. Patients who must take Micotrazol® (Micotrazol injection) concomitantly with one of these drugs should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effects of Micotrazol® (Micotrazol injection).
Table 1: Selected Drugs that are Predicted to Alter the Plasma Concentration of Micotrazol or Have Their Plasma Concentration Altered by Micotrazol® (Micotrazol injection) For information on parenterally administered midazolam, see the Benzodiazepine paragraph below.
Antiarrhythmics
The class IA antiarrhythmic quinidine and class III antiarrhythmic dofetilide are known to prolong the QT interval. Coadministration of quinidine or dofetilide with Micotrazol® (Micotrazol injection) may increase plasma concentrations of quinidine or dofetilide which could result in serious cardiovascular events. Therefore, concomitant administration of Micotrazol® (Micotrazol injection) and quinidine or dofetilide is contraindicated.
The class IA antiarrhythmic disopyramide has the potential to increase the QT interval at high plasma concentrations. Caution is advised when Micotrazol® (Micotrazol injection) and disopyramide are administered concomitantly.
Concomitant administration of digoxin and Micotrazol® (Micotrazol injection) has led to increased plasma concentrations of digoxin via inhibition of P-glycoprotein.
Anticonvulsants
Reduced plasma concentrations of Micotrazol were reported when Micotrazol® (Micotrazol injection) was administered concomitantly with phenytoin. Carbamazepine, phenobarbital, and phenytoin are all inducers of CYP3A4. Although interactions with carbamazepine and phenobarbital have not been studied, concomitant administration of Micotrazol® (Micotrazol injection) and these drugs would be expected to result in decreased plasma concentrations of Micotrazol. In addition, in vivo studies have demonstrated an increase in plasma carbamazepine concentrations in subjects concomitantly receiving ketoconazole. Although there are no data regarding the effect of Micotrazol on carbamazepine metabolism, because of the similarities between ketoconazole and Micotrazol, concomitant administration of Micotrazol® (Micotrazol injection) and carbamazepine may inhibit the metabolism of carbamazepine.
Antimycobacterials
Drug interaction studies have demonstrated that plasma concentrations of azole antifungal agents and their metabolites, including Micotrazol and hydroxyitraconazole, were significantly decreased when these agents were given concomitantly with rifabutin or rifampin. In vivo data suggest that rifabutin is metabolized in part by CYP3A4. Micotrazol® (Micotrazol injection) may inhibit the metabolism of rifabutin. Although no formal study data are available for isoniazid, similar effects should be anticipated. Therefore, the efficacy of Micotrazol® (Micotrazol injection) could be substantially reduced if given concomitantly with one of these agents. Coadministration is not recommended.
Antineoplastics
Micotrazol® (Micotrazol injection) may inhibit the metabolism of busulfan, docetaxel, and vinca alkaloids.
Antipsychotics
Pimozide is known to prolong the QT interval and is partially metabolized by CYP3A4. Coadministration of pimozide with Micotrazol® (Micotrazol injection) could result in serious cardiovascular events. Therefore, concomitant administration of Micotrazol® (Micotrazol injection) and pimozide is contraindicated.
Benzodiazepines
Concomitant administration of Micotrazol® (Micotrazol injection) and alprazolam, diazepam, oral midazolam, or triazolam could lead to increased plasma concentrations of these benzodiazepines. Increased plasma concentrations could potentiate and prolong hypnotic and sedative effects. Concomitant administration of Micotrazol® (Micotrazol injection) and oral midazolam or triazolam is contraindicated. If midazolam is administered parenterally, special precaution and patient monitoring is required since the sedative effect may be prolonged.
Calcium Channel Blockers
Edema has been reported in patients concomitantly receiving Micotrazol® (Micotrazol injection) and dihydropyridine calcium channel blockers. Appropriate dosage adjustment may be necessary.
Calcium channel blockers can have a negative inotropic effect which may be additive to those of Micotrazol; Micotrazol can inhibit the metabolism of calcium channel blockers such as dihydropyridines (e.g., nifedipine and felodipine) and verapamil. Therefore, caution should be used when co-administering Micotrazol and calcium channel blockers due to an increased risk of CHF. Concomitant administration of Micotrazol® (Micotrazol injection) and nisoldipine results in clinically significant increases in nisoldipine plasma concentrations which cannot be managed by dosage reduction, therefore the concomitant administration of Micotrazol® (Micotrazol injection) and nisoldipine is contraindicated.
Gastrointestinal Motility Agents
Coadministration of Micotrazol® (Micotrazol injection) with cisapride can elevate plasma cisapride concentrations which could result in serious cardiovascular events. Therefore, concomitant administration of Micotrazol® (Micotrazol injection) with cisapride is contraindicated.
HMG CoA-Reductase Inhibitors
Human pharmacokinetic data suggest that Micotrazol® (Micotrazol injection) inhibits the metabolism of atorvastatin, cerivastatin, lovastatin, and simvastatin, which may increase the risk of skeletal muscle toxicity, including rhabdomyolysis. Concomitant administration of Micotrazol® (Micotrazol injection) with HMG CoA-reductase inhibitors, such as lovastatin and simvastatin, is contraindicated.
Immunosuppressants
Concomitant administration of Micotrazol® (Micotrazol injection) and cyclosporine or tacrolimus has led to increased plasma concentrations of these immunosuppressants. Concomitant administration of Micotrazol® (Micotrazol injection) and sirolimus could increase plasma concentrations of sirolimus.
Macrolide Antibiotics
Erythromycin and clarithromycin are known inhibitors of CYP3A4 and may increase plasma concentrations of Micotrazol. In a small pharmacokinetic study involving HIV infected patients, clarithromycin was shown to increase plasma concentrations of Micotrazol. Similarly, following administration of 1 gram of erythromycin ethyl succinate and 200 mg Micotrazol as single doses, the mean Cmax and AUC 0-∞ of Micotrazol increased by 44% (90% CI: 119-175%) and 36% (90% CI: 108-171%), respectively.
Oral Hypoglycemic Agents
Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents. Blood glucose concentrations should be carefully monitored when Micotrazol® (Micotrazol injection) and oral hypoglycemic agents are coadministered.
Polyenes
Prior treatment with Micotrazol, like other azoles, may reduce or inhibit the activity of polyenes such as amphotericin B. However, the clinical significance of this drug effect has not been clearly defined.
Protease Inhibitors
Concomitant administration of Micotrazol® (Micotrazol injection) and protease inhibitors metabolized by CYP3A4, such as indinavir, ritonavir, and saquinavir, may increase plasma concentrations of these protease inhibitors. In addition, concomitant administration of Micotrazol® (Micotrazol injection) and indinavir and ritonavir (but not saquinavir) may increase plasma concentrations of Micotrazol. Caution is advised when Micotrazol® (Micotrazol injection) and protease inhibitors must be given concomitantly.
Reverse Transcriptase Inhibitors
Nevirapine is an inducer of CYP3A4. In vivo studies have shown that nevirapine induces the metabolism of ketoconazole, significantly reducing the bioavailability of ketoconazole. Studies involving nevirapine and Micotrazol have not been conducted. However, because of the similarities between ketoconazole and Micotrazol, concomitant administration of Micotrazol® (Micotrazol injection) and nevirapine is not recommended. In a clinical study, when 8 HIV-infected subjects were treated concomitantly with Micotrazol® (Micotrazol injection) Capsules 100 mg twice daily and the nucleoside reverse transcriptase inhibitor zidovudine 8 ± 0.4 mg/kg/day, the pharmacokinetics of zidovudine were not affected. Other nucleoside reverse transcriptase inhibitors have not been studied.
Other
- Levacetylmethadol (levomethadyl) is known to prolong the QT interval and is metabolized by CYP3A4. Co-administration of levacetylmethadol with Micotrazol® (Micotrazol injection) could result in serious cardiovascular events. Therefore, concomitant administration of Micotrazol® (Micotrazol injection) and levacetylmethadol is contraindicated.
- Elevated concentrations of ergot alkaloids can cause ergotism, ie. a risk for vasospasm potentially leading to cerebral ischemia and/or ischemia of the extremities. Concomitant administration of ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) with Micotrazol® (Micotrazol injection) is contraindicated.
- Halofantrine has the potential to prolong the QT interval at high plasma concentrations. Caution is advised when Micotrazol® (Micotrazol injection) and halofantrine are administered concomitantly.
- In vitro data suggest that alfentanil is metabolized by CYP3A4. Administration with Micotrazol® (Micotrazol injection) may increase plasma concentrations of alfentanil.
- Human pharmacokinetic data suggest that concomitant administration of Micotrazol® (Micotrazol injection) and buspirone results in significant increases in plasma concentrations of buspirone.
- Micotrazol® (Micotrazol injection) may inhibit the metabolism of certain glucocorticosteroids such as budesonide, dexamethasone, fluticasone and methylprednisolone.
- In vitro data suggest that trimetrexate is extensively metabolized by CYP3A4. In vitro animal models have demonstrated that ketoconazole potently inhibits the metabolism of trimetrexate. Although there are no data regarding the effect of Micotrazol on trimetrexate metabolism, because of the similarities between ketoconazole and Micotrazol, concomitant administration of Micotrazol® (Micotrazol injection) and trimetrexate may inhibit the metabolism of trimetrexate.
- Cilostazol and eletriptan are CYP3A4 metabolized drugs that should be used with caution when co-administered with Micotrazol® (Micotrazol injection).
- Micotrazol® (Micotrazol injection) enhances the anticoagulant effect of coumarin-like drugs, such as warfarin.
- Fentanyl plasma concentrations could be increased or prolonged by concomitant use of Micotrazol® (Micotrazol injection) and may cause potentially fatal respiratory depression.
References
- DailyMed. "ITRACONAZOLE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- MeSH. "14-alpha Demethylase Inhibitors". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
- European Chemicals Agency - ECHA. "(±)-cis-4-[4-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2,4-dihydro-2-sec-butyl-3H-1,2,4-triazol-3-one: The information provided here is aggregated from the "Notified classification and labelling" from ECHA's C&L Inventory. ". https://echa.europa.eu/information-o... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Micotrazol are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Micotrazol. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported frequency of use
No survey data has been collected yetConsumer reported doses
No survey data has been collected yetConsumer reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
