Description and Composition of Spherazole
Spherazole is an antifungal drug that contains Itraconazole as its active pharmaceutical ingredient. It also contains inactive ingredients called excipients in sufficient. Spherazole comes in different dosage forms and strengths. Its common available dosage forms include capsules, injections, oral solutions, creams, and powder.
Pharmacology of Spherazole
Spherazole is inhibitor of the fungal-mediated synthesis of ergosterol (vital component of fungal cell membranes) It has an ability to inhibit cytochrome P450 3A4 CC-3, and because of this its interaction with other medicines shall be monitored cautiously. That has been shown to inhibit both the hedgehog signaling pathway and angiogenesis Functionally, the antiangiogenic activity of itraconazole has been shown to be linked to inhibition of VEGFR2 phosphorylation trafficking. glycosylation, and cholesterol biosynthesis pathways.
Pharmacokinetics of Spherazole
Spherazole has non-linear pharmacokinetics, and consequently it leads to accumulation of itraconazole in plasma during multiple dosing. Within about 15 days concentration reaches to a steady state level with Cmax and AUC values 4 to 7-fold higher than those seen after a single dose.
Absolute bioavailability is 55%. The mean C max at steady state is approximately 2,282 µg/mL. (capsules with food), 1,435 µg/mL (oral solution with food), and 1,963 µg/ml. (oral solution without food). The mean T max at steady state is approximately 4.6 h (capsules) and 2.5h (oral solution).
99.8% of itraconazole and 99.5% of hydroxyitraconazole are protein bound. Volume of distribution VD is 796 L.
Hydroxyitraconazole is the major metabolite. CYP3A4 isoenzyme predominantly metabolizes resulting in several metabolites.
17 hours is the mean elimination half-life of itraconazole after a single dose and increases to 34-42 hours after repetitive dosing. Itraconazole results in excretion of inactive metabolites to about 35% in urine within one week and to about 54% with feces. Renal excretion of the parent drug accounts for <0.03% of the dose, whereas fecal excretion of unchanged drug varies between 3-18% of the dose.
Mode of action of Spherazole
Spherazole inhibits fungal 14a-demethylase which results in a depletion of ergosterol and disruption of membrane synthesis by fungi.
Indications and Uses of Spherazole
Spherazole is used for the treating of fungal infections in both HIV- and non-HIV-infected individuals. It is active against fungal infections such as blastomycosis, aspergillosis, candidiasis and histoplasmosis, as well as fungal infection localized to the toenails and fingernails (onychomycosis). Patients suffering with fever and low white blood cell counts who are likely to have or develop a fungal infection are also treated with it
Contraindications of Spherazole
Coadministration with dofetilide, cisapride, ergot derivatives (eg, methylergonovine, ergonovine, dihydroergotamine, ergotamine,) levacetylmethadol, felodipine, nisoldipinepimozide, quinidine, methadone, triazolam, oral midazolam, or HMG-CoA reductase inhibitors metabolized by the CYP3A enzyme system (eg, simvastatin ,lovastatin); for treatment of onychomycosis in pregnant women or women contemplating pregnancy (capsules); for treatment of onychomycosis in patients with ventricular dysfunction, such as CHF or history of CHF (capsules), or patients with evidence of ventricular dysfunction, such as CHF or a history of CHF, except for the treatment of life-threatening or other serious infections (oral solution); hypersensitivity to any component of the product.
Precautions and Warning
Itraconazole can lead to congestive heart failure. On experiencing any of the following symptoms, stop intake of itraconazole and call your doctor immediately:
- Shortness of breath
- Coughing up white or pink phlegm,
- Excessive tiredness
- Fast heartbeat
- Swelling of the feet, ankles, or legs
- Waking up at night, and
- Sudden weight gain.
Avoid consumption of cisapride, levomethadyl acetate, methadone, dofetilide, quinidine or pimozide while taking itraconazole. Consumption of these medications with itraconazole can lead to a serious irregular heartbeat, which can lead to death. Intake of certain calcium channel blockers such as nisoldipine and felodipine shall be prohibited; certain cholesterol-lowering medications such as lovastatin and simvastatin; ergot-type medications such as bromocriptine, dihydroergotamine, ergoloid mesylates ergotamine; cabergoline, triazolam or midazolam; while taking itraconazole.
Drug and Interaction with Spherazole
Liver metabolism of some drugs is affected because of intake of Itraconazole. It reduces the metabolism, which results in increased blood levels and side effects from the affected drugs. Life-threatening adverse effects occurred when itraconazole was combined with cisapride, quinidine, pimozide, dofetilide, or levomethadyl, verapamil and nisoldipine (calcium channel blockers). Such combinations increase the occurrence of congestive heart failure due to itraconazole. Itraconazole increases blood levels of tacrolimus, cyclosporine and sirolimus. It can also result in increased blood levels of fentanyl or can also lead to prolonged elimination of fentanyl, potentially leading to fatal respiratory depression. Erythromycin, clarithromycin, ritonavir, indinavir increase blood levels of itraconazole by reducing its elimination from the liver, ultimately which results in increased side effects of itraconazole.
Side effects of Spherazole
Stomach pain, diarrhea or loose stools, constipation, gas or bloating, unpleasant taste, sores in or around the mouth, sore or bleeding gums, heartburn, headache, sweating, dizziness, muscle pain or weakness, joint pain; abnormal menstrual periods, nervousness, depression, decreased sexual desire or ability, runny nose and other cold symptoms, hair loss, unusual dreams.
Some side effects can be serious-amplified sensitivity to sunlight: severe skin problems, buzzing in the ears, blurred vision or indistinct vision, inability to control urination or leading to urination more than usual.
Dosage and Administration of Spherazole
Adults: 200 to 400 mg/day. doses higher than 200 mg shall be given in 2 divided doses. Discontinuing the treatment with inadequate dosage period may lead to recurrence.
Adults: 200 mg/day is the usual dose. If there is no obvious improvement, or if there is evidence of progressive fungal disease, 100 mg increments (max, 400 mg/day).
Adults: 100 mg/day for a minimum of 3 weeks. Treatment should be continued for 2 consecutive weeks following resolution of symptoms. Dosages of up to 200 mg/day may be used based on medical judgment of the patient’s response.
Adults: Loading dose of 200 mg 3 times daily for 3 days. Continue treatment for a minimum of 3 months and until clinical parameters and laboratory tests gives indication of the active fungal infection is being subsided.
Onychomycosis of the Fingernails
Adults: 200 mg orally twice a day for 1 week, the dosing should be repeated after 3 weeks without itraconazole for a total of 2 treatment pulses.
Onychomycosis of the Toenails
Adults: 200 mg/day for 12 weeks.
Adults: 100 mg daily for 15 days.
How to Store Spherazole
Store below 30°C. Protect from light.
KEEP MEDICINES OUT OF REACH OF CHILDREN