Duvelisib: (Major) Reduce duvelisib dose to 15 mg dihydrocodeine 30mg po polsku twice every day and monitor for increased toxicity when coadministered with ketoconazole. Coadministration could improve the publicity of duvelisib. Duvelisib is a CYP3A substrate; ketoconazole is a robust CYP3A inhibitor. The rise in exposure to duvelisib is estimated to be roughly 2-fold when used concomitantly with strong CYP3A inhibitors resembling ketoconazole.
Brexpiprazole: (Main) As a result of brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, similar to barbiturates and primidone, are added to brexpiprazole therapy. If these agents are used in combination, the patient needs to be carefully monitored for a lower in brexpiprazole efficacy. When the CYP3A4 inducer is withdrawn from the mix therapy, the brexpiprazole dose should be reduced over 1 to 2 weeks to the original stage.
Ergonovine: (Contraindicated) Coadministration of ergot alkaloids and ketoconazole is contraindicated because of the potential for elevated ergot publicity. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and different tissues. Ergot alkaloids are CYP3A substrates and ketoconazole is a robust CYP3A inhibitor.
Nortriptyline: (Reasonable) Use ketoconazole with caution together with tricyclic antidepressants (TCAs) as concurrent use could enhance the danger of QT prolongation and increased TCA-related antagonistic effects. TCAs share pharmacologic properties much like the class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with increased-dose prescription therapy (elevated serum concentrations). CYP3A4 may be partially concerned in the metabolism of TCAs; ketoconazole might enhance TCA concentrations through inhibition of CYP3A4. In not less than one case, an elevated incidence of TCA-related negative effects, such as dizziness and syncope have occurred together with another azole drug. In another case, QT-prolongation and torsades de pointes occurred. Close clinical monitoring is critical if concurrent use is medically vital.
Cases of neuropathy are uncommon, perhaps because of the everyday brief course of treatment, however with extended and high-dose therapy it can cause a mild but painful distal symmetric sensory neuropathy. Optic neuritis is more frequent, though in a single report most patients with optic neuropathy additionally had evidence of peripheral neuropathy ( sixty two ). .