Interactions
The concomitant use of the following medications is contraindicated with ketoconazole tablets:
methadone, disopyramide, dronedarone
irinotecan, lurasidone, colchicine
alprazolam, oral midazolam, oral triazolam
felodipine, ranolazine, tolvaptan, eplerenone
HMG-CoA reductase inhibitors: lovastatin, simvastatin
ergot alkaloids: ergotamine, dihydroergotamine, ergometrine, methylergometrine
Others: cisapride, nisoldipine, dofetilide, pimozideAnd is not recommended:
carbamazepine, phenytoin
gastric acid suppressants: antacids, antimuscarinics, histamine H2 blockers, proton pump inhibitors
sucralfate
rifampin, rifabutin, isoniazid
efavirenz, nevirapineRitonavir is known for increasing activity of the ketoconazole so it is recommended to reduce dosage.There is also a list of drugs which significantly decrease systemic exposure to the ketoconazole and drugs whose systemic exposure is increased by the ketoconazole. Pharmacology
Pharmacodynamics
Antifungal activity
As an antifungal, ketoconazole is structurally similar to imidazole, and interferes with the fungal synthesis of ergosterol, a constituent of fungal cell membranes, as well as certain enzymes. As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (CYP51A1). This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. Lower doses of fluconazole and itraconazole are required to kill fungi compared to ketoconazole, as they have been found to have a greater affinity for fungal cell membranes. Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans. Experimentally, resistance usually arises as a result of mutations in the sterol biosynthesis pathway. Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. Multidrug-resistance (MDR) genes can also play a role in reducing cellular levels of the drug.
PBA is most commonly observed in people with neurologic injuries such as traumatic brain injury (TBI) and stroke, and neurologic diseases such as dementias including Alzheimers disease, attention deficit/hyperactivity disorder (ADHD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Parkinsons disease (PD). It has been reported as a symptom of hyperthyroidism, Graves disease, or hypothyroidism in combination with depression.PBA has also been observed in association with a variety of other brain disorders, including brain tumors, Wilsons disease, syphilitic pseudobulbar palsy, and various encephalitides. Rarer conditions associated with PBA include gelastic epilepsy, dacrystic epilepsy, central pontine myelinolysis, olivopontinocerebellar atrophy, lipid storage diseases, chemical exposure (e.g., nitrous oxide and insecticides), fou rire prodromique, and Angelman syndrome. It is hypothesized that these primary neurologic injuries and diseases affect chemical signaling in the brain, which in turn disrupts the neurologic pathways that control emotional expression. Stroke
PBA is one of the most frequently reported post-stroke behavioral disorders, with a range of reported prevalence rates from 28% to 52%. The higher prevalence rates tend to be reported in stroke patients who are older or who have a history of prior stroke. The relationship between post-stroke depression and PBA is complicated, because the depressive syndrome also occurs with high frequency in stroke survivors. Post-stroke patients with PBA are more depressed than post-stroke patients without PBA, and the presence of a depressive syndrome may exacerbate the weeping side of PBA symptoms. Multiple sclerosis
Recent studies suggest that approximately 10% of patients with multiple sclerosis (MS) will experience at least one episode of emotional lability.