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Difference Between Itraconazole and Terbinafine

Itraconazole vs Terbinafine

Itraconazole and Terbinafine are the most habitually used antifungal agents. They are best for the treatment of onychomycosis. Onychomycosis is a general fungal infection of the nail. Although approved to be the best antifungal drugs for fungal infections, Itraconazole and Terbinafine are also associated with a number of potentially hazardous drug interactions. Healthcare providers must be aware of these interactions to prevent complications.

Itraconazole capsules require an acidic gastric environment. Thus, it is recommended to be taken with meals for better absorption. Foods stimulate the production of hydrochloric acid. This acid is responsible for the acidic environment in the stomach. To include foods or other agents such as proton pump inhibitors, H-2 antagonists, antacids and the like that can reduce the acidity of the stomach must be avoided in the administration of Itraconazole by one to two hours. In contrast to Itraconazole’s capsule preparation, Itraconazole solution does not need gastric acidity for absorption; thus, it does not need to be administered with a meal. During fasting conditions, the peak concentration and bioavailability of the Itraconazole solution is increased. Itraconazole concentrations stay in the nail for six to nine months after discontinuing therapy. Drugs that may increase concentrations of Itraconazole include Macrolide (Clarithromycin), antibiotics (Erythromycin), Protease (Indinavir), and inhibitors such as Ritonavir. Itraconazole may increase the concentration of the following drugs:

Antiarrhythmics such as Digoxin, Dofetilide, Quinidine

Anticonvulsants such as Carbamazepine

Antimycobacterials (Rifabutin)

Antineoplastics like Busulfan, Docetaxel, Vinca alkaloids

Antipsychotics (Pimozide)

Benzodiazepines such as Alprazolam, Diazepam, Midazolam, Triazolam

Calcium channel blockers like Dihydropyridines, Verapamil

Gastrointestinal motility agents (Cisapride) and

HMG-CoA reductase inhibitors such as Atorvastatin, Lovastatin, Simvastatin.

Complications such as QT prolongation, torsades de pointes, ventricular fibrillation, cardiac arrest, and/or sudden death can occur with coadministration of the above drugs with Itraconazole. Studies have shown an increased risk of skeletal muscle toxicity such as rhabdomyolysis upon coadministration of Itraconazole with HMG-CoA reductase inhibitors. Itraconazole may increase plasma concentrations of benzodiazepines producing sedative effects and hypnotic effects. Patient monitoring and cautions in using this drug must be observed.

Terbinafine, on the other hand, is 70 per cent well absorbed following oral administration. Gastric acidity does not seem to affect the absorption. Terbinafine is highly lipophilic. That is, it has a high affinity to combine or melt with lipids. It is distributed extensively into the tissues. After oral administration, concentrations of the drug are seen in the adipose tissue, stratum corneum, dermis, epidermis, and nails. Terbinafine is 99 per cent protein bound. It is not extensively metabolized by the cytochrome P450 system unlike Itraconazole. Curative concentrations of Terbinafine are available in the nails for up to nine months after discontinued therapy. Drugs that may decrease concentrations of Itraconazole include: anticonvulsants (Carbamazepine, Phenobarbital, Phenytoin) antimycobacterials (Isoniazid, Rifabutin, Rifampin), gastric acid suppressors/neutralizers and Nevirapine. Caution must be observed upon administering Terbinafine to patients receiving Warfarin because, even though not yet proven, studies show that Terbinafine interacts with Warfarin. There are still not enough studies showing the drug’s interactions with contraceptives, hormone replacement therapies, hypoglycemics, Theophylline, Phenytoin, Thiazide, diuretics, beta blockers, and calcium channel blockers. There are no absolute contraindications regarding the use of Terbinafine with other drugs.

Patients receiving Itraconazole and Terbinafine must be monitored, and tests must be done to determine drug toxicity.

Summary:

1.Itraconazole and Terbinafine are the most habitually used antifungal agents. It is best for the treatment of onychomycosis.

2.Although approved to be the best antifungal drugs for fungal infections, Itraconazole and Terbinafine are also associated with a number of potentially hazardous drug interactions.

3.Itraconazole capsules require an acidic gastric environment. Thus, it is recommended to be taken with meals for better absorption.

4.Foods or other agents such as proton pump inhibitors, H-2 antagonists, antacids and the like that can reduce the acidity of the stomach must be avoided in the administration of Itraconazole by one to two hours. In contrast to Itraconazole’s capsule preparation, Itraconazole solution does not need gastric acidity for absorption; thus, it does not need to be administered with a meal.

5.Drugs that may increase the concentrations of Itraconazole include: Macrolide (Clarithromycin), antibiotics (Erythromycin), Protease (Indinavir), and inhibitors such as Ritonavir. Itraconazole may increase the concentration of the following drugs: Antiarrhythmics such as Digoxin, Dofetilide, Quinidine; anticonvulsants such as Carbamazepine; antimycobacterials (Rifabutin); antineoplastics like Busulfan, Docetaxel, Vinca alkaloids; antipsychotics (Pimozide); benzodiazepines such as Alprazolam, Diazepam, Midazolam, Triazolam; calcium channel blockers like Dihydropyridines, Verapamil; gastrointestinal motility agents (Cisapride), and HMG-CoA reductase inhibitors such as Atorvastatin, Lovastatin, Simvastatin.

6.Terbinafine, on the other hand, is 70 per cent well absorbed following oral administration. Gastric acidity does not seem to affect the absorption.

7.Drugs that may decrease concentrations of Itraconazole include: anticonvulsants (Carbamazepine, Phenobarbital, Phenytoin), antimycobacterials (Isoniazid, Rifabutin, Rifampin), gastric acid suppressors/neutralizers, and Nevirapine.


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