Nizoral

Nizoral - General Information

Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [PubChem]

 

Pharmacology of Nizoral

Nizoral, like clotrimazole, fluconazole, itraconazole, and miconazole, is an imidazole antifungal agent.

 

Nizoral for patients

Shampoo: May be irritating to mucous membranes of the eyes and contact with this area should be avoided.

There have been reports that use of the shampoo resulted in removal of the curl from permanently waved hair.

Tablet: Patients should be instructed to report any signs and symptoms which may suggest liver dysfunction so that appropriate biochemical testing can be done. Such signs and symptoms may include unusual fatigue, anorexia, nausea and/or vomiting, jaundice, dark urine or pale stools

 

Nizoral Interactions

Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. Coadministration of NIZORAL Tablets 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. The following drug interactions have been identified involving NIZORAL Tablets and other drugs metabolized by the cytochrome P450 3A4 enzyme system:

Ketoconazole tablets inhibit the metabolism of terfenadine, resulting in an increased plasma concentration of terfenadine and a delay in the elimination of its acid metabolite. The increased plasma concentration of terfenadine or its metabolite may result in prolonged QT intervals.

Pharmacokinetic data indicate that oral ketoconazole inhibits the metabolism of astemizole, resulting in elevated plasma levels of astemizole and its active metabolite desmethylastemizole which may prolong QT intervals. Coadministration of astemizole with ketoconazole tablets is therefore contraindicated.

Human pharmacokinetics data indicate that oral ketoconazole potently inhibits the metabolism of cisapride resulting in a mean eight-fold increase in AUC of cisapride. Data suggest that coadministration of oral ketoconazole and cisapride can result in prolongation of the QT interval on the ECG. Therefore concomitant administration of ketoconazole tablets with cisapride is contraindicated.

Ketoconazole tablets may alter the metabolism of cyclosporine, tacrolimus, and methylprednisolone, resulting in elevated plasma concentrations of the latter drugs. Dosage adjustment may be required if cyclosporine, tacrolimus, or methylprednisolone are given concomitantly with NIZORAL Tablets.

Coadministration of NIZORAL Tablets with midazolam or triazolam has resulted in elevated plasma concentrations of the latter two drugs. This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. These agents should not be used in patients treated with NIZORAL Tablets. If midazolam is administered parenterally, special precaution is required since the sedative effect may be prolonged.

Rare cases of elevated plasma concentrations of digoxin have been reported. It is not clear whether this was due to the combination of therapy. It is, therefore, advisable to monitor digoxin concentrations in patients receiving ketoconazole.

When taken orally, imidazole compounds like ketoconazole may enhance the anticoagulant effect of coumarin-like drugs. In simultaneous treatment with imidazole drugs and coumarin drugs, the anticoagulant effect should be carefully titrated and monitored.

Because severe hypoglycemia has been reported in patients concomitantly receiving oral miconazole (an imidazole) and oral hypoglycemic agents, such a potential interaction involving the latter agents when used concomitantly with ketoconazole tablets (an imidazole) can not be ruled out.

Concomitant administration of ketoconazole tablets with phenytoin may alter the metabolism of one or both of the drugs. It is suggested to monitor both ketoconazole and phenytoin.

Concomitant administration of rifampin with ketoconazole tablets reduces the blood levels of the latter. INH (Isoniazid) is also reported to affect ketoconazole concentrations adversely. These drugs should not be given concomitantly.

After the coadministration of 200 mg oral ketoconazole twice daily and one 20 mg dose of loratadine to 11 subjects, the AUC and C_max of loratadine averaged 302% (± 142 S.D.) and 251% (± 68 S.D.), respectively, of those obtained after co-treatment with placebo. The AUC and C_max of descarboethoxyloratadine, an active metabolite, averaged 155% (± 27 S.D.) and 141% (± 35 S.D.), respectively. However, no related changes were noted in the QT₀ on ECG taken at 2, 6, and 24 hours after the coadministration. Also, there were no clinically significant differences in adverse events when loratadine was administered with or without ketoconazole.

Rare cases of a disulfiram-like reaction to alcohol have been reported. These experiences have been characterized by flushing, rash, peripheral edema, nausea, and headache. Symptoms resolved within a few hours.

 

Nizoral Contraindications

Tablets and Shampoo

Ketoconazole is contraindicated in patients who have shown hypersensitivity to the drug or excipients of the formulation(s).

Tablets

Coadministration of terfenadine or astemizole with ketoconazole tablets is contraindicated.

Concomitant administration of NIZORAL® Tablets with oral triazolam is contraindicated.

NIZORAL is contraindicated in patients who have shown hypersensitivity to the drug.

 

Additional information about Nizoral

Nizoral Indication: For the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis.
Mechanism Of Action: Nizoral interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Nizoral can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone.
Drug Interactions: Alfentanil The imidazole increases the effect and toxicity of alfentanil
Alprazolam The imidazole increases the effect of the benzodiazepine
Amitriptyline The imidazole increases the effect and toxicity of the tricyclic
Anisindione The imidazole increases the effect of the anticoagulant
Aripiprazole The imidazole increases the effect of aripiprazole
Bosentan The imidazole increases the effect and toxicity of bosentan
Budesonide The imidazole increases levels/effect of budesonide
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 immunosuppressant
Diazepam The imidazole increases the effect of the benzodiazepine
Dicumarol The imidazole increases the effect of the anticoagulant
Acenocoumarol The imidazole increases the effect of the anticoagulant
Warfarin The imidazole increases the effect of the anticoagulant
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
Imipramine The imidazole increases the effect and toxicity of the tricyclic
Methylprednisolone The imidazole increases the effect and toxicity of the corticosteroid
Midazolam The imidazole increases the effect of the benzodiazepine
Nortriptyline The imidazole increases the effect and toxicity of the tricyclic
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
Ramelteon The imidazole increases the levels/toxicity of ramelteon
Ritonavir The imidazole increases the effect and toxicity of ritonavir
Saquinavir The imidazole increases the effect and toxicity of saquinavir
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
Tadalafil The imidazole increases tadalafil levels
Tolterodine The imidazole increases the effect and toxicity of tolterodine
Triazolam The imidazole increases the effect of the benzodiazepine
Valdecoxib The imidazole increases the effect and toxicity of valdecoxib
Vardenafil The imidazole increases the effect and toxicity of vardenafil
Vinblastine The imidazole increases the effect and toxicity of vinblastine
Vincristine The imidazole increases the effect and toxicity of the antineoplasic
Ziprasidone Nizoral increases the effect and toxicity of ziprasidone
Tolbutamide Nizoral increases the effect and toxicity of tolbutamide
Sibutramine Nizoral increases the levels and toxicity of sibutramine
Rosiglitazone Nizoral increases the effect of rosiglitazone
Quetiapine Nizoral increases the effect/toxicity of quetiapine
Pioglitazone Nizoral increases the effect of pioglitazone
Galantamine Nizoral increases the effect and toxicity of galantamine
Indinavir Nizoral increases the effect of indinavir
Irinotecan Nizoral increases the effect and toxicity of irinotecan
Trazodone This strong CYP3A4 inhibitor increases the effect and toxicity of trazodone
Sunitinib Possible increase in sunitinib levels
Sucralfate Sucralfate decreases the absorption of the imidazole
Solifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Alfuzosin The antifungal increases the effect of alfuzosin
Almotriptan This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Aprepitant This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
Ciclesonide Increased effects/toxicity of ciclesonide
Darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism
Docetaxel The agent increases the serum levels and toxicity of docetaxel
Dofetilide This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide
Eletriptan This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Gefitinib This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Isoniazid Isoniazid decreases the effect of ketoconazole
Nevirapine Nevirapine decreases the effect of ketoconazole
Rifampin Rifampin dereases the effect of the imidazole
Ranolazine Increased levels of ranolazine - risk of toxicity
Terfenadine Increased risk of cardiotoxicity and arrhythmias
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
Aluminium The antacid decreases the effect of the imidazole
Bismuth The antacid decreases the effect of the imidazole
Magnesium The antacid decreases the effect of the imidazole
Magnesium oxide The antacid decreases the effect of the imidazole
Calcium The antacid decreases the effect of the imidazole
Buspirone The macrolide increases the effect and toxicity of buspirone
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
Ranitidine The anti-H2 decreases the absorption of the imidazole
Dihydroergotamine Possible ergotism and sever ischemia with this combination
Ergotamine Possible ergotism and sever ischemia with this combination
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
Rabeprazole The proton pump inhibitor decreases the absorption of imidazole
Ethinyl Estradiol This anti-infectious agent could decrease the effect of the oral contraceptive
Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
Food Interactions: Avoid alcohol.
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.
Generic Name: Ketoconazole
Synonyms: Not Available
Drug Category: Antifungals
Drug Type: Small Molecule; Approved

Other Brand Names containing Ketoconazole: Extina; Fungarest; Fungoral; Ketocanazole; Ketoconazol; Ketoconazol [Inn-Spanish]; Ketoconazole [Usan-Ban-Inn-Jan]; Ketoconazolum [Inn-Latin]; Ketoderm; Ketoisdin; Ketozole; Nizoral; Nizoral Cream; Nizoral Shampoo; Nizoral a-D; Nizoral a-D Shampoo; Orifungal; Orifungal M; Panfungol;
Absorption: Moderate
Toxicity (Overdose): Hepatotoxicity, LD₅₀=86 mg/kg (orally in rat)
Protein Binding: 99% (in vitro, plasma protein binding)
Biotransformation: Hepatic
Half Life: 2 hours
Dosage Forms of Nizoral: Tablet Oral
Cream Topical
Shampoo Topical
Chemical IUPAC Name: 1-[4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone
Chemical Formula: C26H28Cl2N4O4
Ketoconazole on Wikipedia: https://en.wikipedia.org/wiki/Ketoconazole
Organisms Affected: Fungi