Sporanos
Sporanos - General Information
One of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem]
Pharmacology of Sporanos
Sporanos is an imidazole/triazole type antifungal agent. Sporanos is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Sporanos exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.
Sporanos for patients
Sporanos Interactions
Both itraconazole and its major metabolite, hydroxyitraconazole, are inhibitors of the cytochrome P450 3A4 enzyme system. Coadministration of Itraconazole and drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Therefore, unless otherwise specified, appropriate dosage adjustments may be necessary.
Coadministration of terfenadine with Itraconazole has led to elevated plasma concentrations of terfenadine, resulting in rare instances of life- threatening cardiac dysrhythmias and one death.
Another oral azole antifungal, ketoconazole, inhibits the metabolism of astemizole, resulting in elevated plasma concentrations of astemizole and its active metabolite desmethylastermizole which may prolong QT intervals. In vitro data suggest that itraconazole, when compared to ketoconazole, has a less pronounced effect on the biotransformation system responsible for the metabolism of astemizole. Based on the chemical resemblance of itraconazole and ketoconazole, coadministration of astemizole with itraconazole is contraindicated.
Human pharmacokinetics data indicate that oral ketoconazole potently inhibits the metabolism of cisapride resulting in an eight-fold increase in the mean AUC of cisapride. Data suggest that coadministration of oral ketoconazole and cisapride can result in prolongation of the QT interval on the ECG. In vitro data suggest that itraconazole also markedly inhibits the biotransformation system mainly responsible for the metabolism of cisapride; therefore concomitant administration of Itraconazole with cisapride is contraindicated.
Coadministration of Itraconazole with oral midazolam or triazolam has resulted in elevated plasma concentrations of the latter two drugs. This may potentiate and prolong hypnotic and sedative effects. These agents should not be used in patients treated with Itraconazole. If midazolam is administered parenterally, special precaution is required since the sedative effect may be prolonged.
Coadministration of Itraconazole and cyclosporine, tacrolimus or digoxin has led to increased plasma concentrations of the latter three drugs. Cyclosporine, tacrolimus and digoxin concentrations should be monitored at the initiation of Itraconazole therapy and frequently thereafter, and the dose of these three drug products adjusted appropriately.
There have been rare reports of rhabdomyolysis involving renal transplant patients receiving the combination of Itraconazole, cyclosporine, and the HMG-CoA reductase inhibitors lovastatin or simvastatin. Rhabdomyolysis has been observed in patients receiving HMG-CoA reductase inhibitors administered alone (at recommended dosages) or concomitantly with immunosuppressive drugs including cyclosporine.
When Itraconazole was coadministered with phenytoin, rifampin, or H2antagonists, reduced plasma concentrations of itraconazole were reported. The physician is advised to monitor the plasma concentrations of itraconazole when any of these drugs is taken concurrently, and to increase the dose of Itraconazole if necessary. Although no studies have been conducted, concomitant administration of Itraconazole and phenytoin may alter the metabolism of phenytoin; therefore, plasma concentrations of phenytoin should also be monitored when it is given concurrently with Itraconazole.
It has been reported that Itraconazole enhances the anticoagulant effect of coumarin-like drugs. Therefore, prothrombin time should be carefully monitored in patients receiving Itraconazole and coumarin-like drugs simultaneously.
Plasma concentrations of azole antifungal agents are reduced when given concurrently with isoniazid. Itraconazole plasma concentrations should be monitored when Itraconazole and isoniazid are coadministered.
Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents. Blood glucose concentrations should be carefully monitored when Itraconazole and oral hypoglycemic agents are coadministered.
Tinnitus and decreased hearing have been reported in patients concomitantly receiving Itraconazole and quinidine. Edema has been reported in patients concomitantly receiving Itraconazole and dihydropyridine calcium channel blockers. Appropriate dosage adjustments may be necessary.
The results from a study in which eight HIV-infected individuals were treated with zidovudine, 8 +/- 0.4 mg/kg/day, showed that the pharmacokinetics of zidovudine were not affected during concomitant administration of Itraconazole, 100 mg b.i.d.
Sporanos Contraindications
Coadministration of terfenadine, astemizole or cisapride with Sporanox (itraconazole capsules) is contraindicated.
Concomitant administration of Sporanox with oral triazolam or with oral midazolam is contraindicated..
Sporanox should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy.
Sporanox is contraindicated in patients who have shown hypersensitivity to the drug or its excipients. There is no information regarding cross hypersensitivity between itraconazole and other azole antifungal agents. Caution should be used in prescribing Sporanox to patients with hypersensitivity to other azoles.
Additional information about Sporanos
Sporanos Indication: For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
Mechanism Of Action: Sporanos interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Sporanos may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
Drug Interactions: Alfentanil The imidazole increases the effect and toxicity of alfentanil
Alfuzosin The antifungal increases the effect of alfuzosin
Almotriptan This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Aprepitant This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Eletriptan This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Dofetilide This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
Erlotinib This potent CYP3A4 inhibitor increases levels/toxicity of erlotinib
Gefitinib This potent CYP3A4 inhibitor increases levels/toxicity of gefitinib
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Trazodone This potent CYP3A4 inhibitor increases the effect and toxicity of trazodone
Alprazolam The imidazole increases the effect of the benzodiazepine
Aripiprazole The imidazole increases the effect of aripiprazole
Bosentan The imidazole increases the effect and toxicity of bosentan
Carbamazepine The imidazole increases the effect of carbamazepine
Chlordiazepoxide The imidazole increases the effect of the benzodiazepine
Cilostazol The imidazole increases the effect of cilostazol
Cinacalcet The imidazole increases the effect and toxicity of cinacalcet
Clonazepam The imidazole increases the effect of the benzodiazepine
Clorazepate The imidazole increases the effect of the benzodiazepine
Cyclosporine The imidazole increases the effect of the immunosuppressant
Diazepam The imidazole increases the effect of the benzodiazepine
Digoxin Sporanos increases the effect of digoxin
Budesonide The imidazole increases levels/effect of budesonide
Eplerenone The imidazole increases the effect and toxicity of eplerenone
Estazolam The imidazole increases the effect of the benzodiazepine
Everolimus The imidazole increases everolimus levels/toxicity
Fentanyl The imidazole increases levels/toxicity of fentanyl
Flurazepam The imidazole increases the effect of the benzodiazepine
Halazepam The imidazole increases the effect of the benzodiazepine
Haloperidol The imidazole increases the effect and toxicity of haloperidol
Imatinib The imidazole increases the levels of imatinib
Methylprednisolone The imidazole increases the effect and toxicity of the corticosteroid
Midazolam The imidazole increases the effect of the benzodiazepine
Prednisolone The imidazole increases the effect and toxicity of the corticosteroid
Prednisone The imidazole increases the effect and toxicity of the corticosteroid
Quazepam The imidazole increases the effect of the benzodiazepine
Quinidine The imidazole increases the effect and toxicity of quinidine
Quinidine barbiturate The imidazole increases the effect and toxicity of quinidine
Ritonavir The imidazole increases the effect and toxicity of ritonavir
Sildenafil The imidazole increases the effect and toxicity of sildenafil
Sirolimus The imidazole increases the effect and toxicity of sirolimus
Tacrolimus The imidazole increases the effect of immunosuppressant
Tolterodine The imidazole increases the effect and toxicity of tolterodine
Triazolam The imidazole increases the effect of the benzodiazepine
Vardenafil The imidazole increases the effect and toxicity of vardenafil
Vinblastine The imidazole increases the effect and toxicity of the antineoplasic
Vincristine The imidazole increases the effect and toxicity of the antineoplasic
Warfarin The imidazole increases the effect of the anticoagulant
Acenocoumarol The imidazole increases the effect of the anticoagulant
Dicumarol The imidazole increases the effect of the anticoagulant
Anisindione The imidazole increases the effect of the anticoagulant
Aluminium The antacid decreases the effect of the imidazole
Bismuth The antacid decreases the effect of the imidazole
Calcium The antacid decreases the effect of the imidazole
Felodipine Increases effect/toxicity of felodipine
Magnesium The antacid decreases the effect of the imidazole
Magnesium oxide The antacid decreases the effect of the imidazole
Levomethadyl Acetate Sporanos increases the effect/toxicity of levomethadyl
Risperidone Increases the level of risperidone
Sucralfate Sucralfate decreases the absorption of the imidazole
Sunitinib Possible increase in sunitinib levels
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Rifampin Rifampin decreases the effect of the imidazole
Rifabutin Rifabutin decreases the effect of itraconazole
Pimozide Increased risk of cardiotoxicity and arrhythmias
Cisapride Increased risk of cardiotoxicity and arrhythmias
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Increased risk of myopathy/rhabdomyolysis
Cerivastatin Increased risk of myopathy/rhabdomyolysis
Lovastatin Increased risk of myopathy/rhabdomyolysis
Simvastatin Increased risk of myopathy/rhabdomyolysis
Simvastatin Increased risk of myopathy/rhabdomyolysis
Ranolazine Increased levels of ranolazine - risk of toxicity
Ranitidine The anti-H2 decreases the absorption of the imidazole
Cimetidine The anti-H2 decreases the absorption of the imidazole
Famotidine The anti-H2 decreases the absorption of the imidazole
Nizatidine The anti-H2 decreases the absorption of the imidazole
Rabeprazole The proton pump inhibitor decreases the absorption of imidazole
Esomeprazole The proton pump inhibitor decreases the absorption of imidazole
Lansoprazole The proton pump inhibitor decreases the absorption of imidazole
Omeprazole The proton pump inhibitor decreases the absorption of imidazole
Pantoprazole The proton pump inhibitor decreases the absorption of imidazole
Phenytoin Phenytoin decreases the effect of itraconazole
Mephenytoin Phenytoin decreases the effect of itraconazole
Fosphenytoin Phenytoin decreases the effect of itraconazole
Ethotoin Phenytoin decreases the effect of itraconazole
Phenobarbital The barbiturate decreases the effect of itraconazole
Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
Buspirone The macrolide increases the effect and toxicity of buspirone
Ciclesonide Increased effects/toxicity of ciclesonide
Celiprolol Itaconazole increases levels/effect of celiprolol
Clarithromycin The macrolide increases the effect and toxicity of itraconazole
Josamycin The macrolide increases the effect and toxicity of itraconazole
Erythromycin The macrolide increases the effect and toxicity of itraconazole
Ethinyl Estradiol This anti-infectious agent could decreases the effect of the oral contraceptive
Dihydroergotamine Possible ergotism and severe ischemia with this combination
Ergotamine Possible ergotism and severe ischemia with this combination
Food Interactions: Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
Take with food.
Avoid taking with grapefruit juice.
Take after a full meal.
Generic Name: Itraconazole
Synonyms: ITC; ITCZ; ITR; Itraconazol [Spanish]; Itraconazolum [Latin]; ITZ
Drug Category: Antiprotozoals; Antifungals
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Itraconazole: Itrizole; Oriconazole; Sporal; Sporanos; Sporanox; Sporonox; Triasporn;
Absorption: The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.
Toxicity (Overdose): No significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.
Protein Binding: 99.8%
Biotransformation: Itraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission.
Half Life: 21 hours
Dosage Forms of Sporanos: Liquid Oral
Capsule Oral
Chemical IUPAC Name: 2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one
Chemical Formula: C35H38Cl2N8O4
Itraconazole on Wikipedia: https://en.wikipedia.org/wiki/Itraconazole
Organisms Affected: Fungi, yeast and protozoans
