Fluconazole

Explanation

Fluconazole is a moderate CYP3A4 inhibitor. Carbamazepine is mainly metabolised by CYP3A4. Co-administration may increase carbamazepine levels 20-40%, with risk of toxicity (nausea, diplopia, ataxia, nystagmus). Monitor carbamazepine levels (target: 4-12 μg/mL) and signs of toxicity weekly during co-administration.

Explanation

Rifampicin induces CYP2C9 and CYP3A4, pathways of fluconazole metabolism, and can reduce its concentrations by about 25–50% and shorten the half-life; the antifungal effect may be compromised in severe infections. Monitor the clinical response and consider increasing the fluconazole dose during the combination, monitoring liver function.

Explanation

Mefloquine can prolong the QTc interval, especially when combined with other drugs that alter cardiac conduction or prolong the QT — the label explicitly contraindicates halofantrine and ketoconazole (risk of potentially fatal QT prolongation) and advises against quinine/quinidine; the patient guide recommends not taking it with QT-prolonging drugs. Fluconazole also prolongs the QT (torsade de pointes in post-marketing experience) and, as a CYP3A4 inhibitor, may also raise mefloquine levels. The combination should be avoided (in practice, antimalarial prophylaxis and antifungal treatment rarely overlap, but they can occur in patients with invasive fungal infections); if unavoidable, monitor the ECG, electrolytes and correct hypokalaemia/hypomagnesaemia.

Explanation

Chloroquine prolongs the QT interval (torsade de pointes and ventricular arrhythmias reported, with a higher risk at high doses and with concomitant QT-prolonging drugs — the chloroquine label explicitly warns about this risk), and fluconazole can also prolong the QT (the label contraindicates fluconazole with QT-prolonging CYP3A4-metabolised drugs). The combination adds up the risk of ventricular arrhythmias, especially in patients with long QT, hypokalaemia, hypomagnesaemia, bradycardia or cardiac disease. Whenever possible, avoid or choose an alternative antifungal; if unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.

Explanation

Fluconazole inhibits CYP3A4 (to a variable degree depending on dose) and can raise atorvastatin concentrations, increasing the risk of myopathy/rhabdomyolysis, especially with high fluconazole doses or prolonged courses. Monitor muscle symptoms and CK, use the lowest effective statin dose during antifungal treatment and instruct the patient to stop in the presence of muscle pain, weakness or dark urine. In patients with renal impairment, the risk is higher.

Explanation

Quinine prolongs the QT interval consistently and in a dose-dependent way, with a risk of potentially fatal ventricular arrhythmias (torsade de pointes, ventricular fibrillation), and the label contraindicates its use in patients with QT prolongation and recommends avoiding other QT-prolonging drugs. Quinine is predominantly metabolised by CYP3A4, and inhibitors of this enzyme raise its concentrations — the label documents ketoconazole increasing quinine AUC by 45% and links CYP3A4 inhibition to a fatal torsade de pointes case (erythromycin+quinine). Fluconazole combines both risks: it prolongs the QT (torsade de pointes in post-marketing experience) and inhibits CYP3A4, potentiating quinine toxicity (cinchonism, cardiotoxicity, hypoglycaemia). Whenever possible, avoid the combination; if unavoidable, monitor the ECG, electrolytes (correct hypokalaemia/hypomagnesaemia) and signs of quinine toxicity.

Explanation

Explanation

Fluconazole inhibits CYP3A4, one of the metabolic pathways for roflumilast. Roflumilast and N-oxide metabolite levels may increase 20-30%. Monitor GI adverse effects (diarrhoea, nausea) and liver function. Reduce dose if necessary.

Explanation

Prednisolone is metabolised by CYP3A4. Fluconazole inhibits CYP3A4, increasing prednisolone exposure. The effect may be significant at high doses. Monitor for signs of hypercortisolism (elevated glucose, weight gain, hypertension, osteoporosis). Consider reducing prednisolone dose by 25-50%.

Explanation

Explanation

Explanation

Explanation

Glimepiride is metabolised by CYP2C9; fluconazole is one of the most potent inhibitors of this isoenzyme. An in vivo study cited in the SmPC (EMC-UK) shows an approximately 2-fold increase in glimepiride AUC with fluconazole. The resulting hypoglycaemia can be severe and prolonged, especially in the elderly and in patients with impaired renal function. This is a common combination in community pharmacy (vaginal/oral candidiasis in diabetic patients).

Explanation

The gliclazide SmPC (EMC-UK) lists fluconazole among the drugs that potentiate the hypoglycaemic effect of sulfonylureas, with possible symptomatic hypoglycaemia or coma. The mechanism involves inhibition of CYP2C9 (gliclazide metabolism) and excretion. Blood glucose monitoring is mandatory during the combination.

Explanation

Fluconazole is a potent inhibitor of CYP2C9, the isoenzyme that metabolises active S-warfarin; the effect is dose-dependent and more marked at high doses (e.g. 400 mg/day). The inhibition raises warfarin levels and the INR, with significant bleeding risk — a well-documented interaction mentioned in the approved fluconazole and warfarin labels. Reduce the warfarin dose when starting fluconazole, monitor the INR frequently and re-adjust after the antifungal is stopped; watch for bleeding signs.

Explanation

Fluconazole inhibits CYP2C9 and CYP3A4, the enzymes that metabolise glyburide (a sulfonylurea); in the pharmacokinetic study of the fluconazole label with 20 volunteers, glyburide (5 mg single dose) AUC and Cmax increased significantly after fluconazole administration — AUC +44% ± 29% and Cmax +19% ± 19% — and 5 of the 20 volunteers required oral glucose after glyburide ingestion at 7 days of fluconazole. Across the three sulfonylurea studies (tolbutamide, glipizide, glyburide), 47.8% of fluconazole-treated patients experienced symptoms consistent with hypoglycaemia. The label recommends carefully monitoring blood glucose and adjusting the sulfonylurea dose as necessary. In practice, warn the patient about hypoglycaemia signs (sweating, tremor, palpitations, confusion) and consider reducing the glyburide dose or preferring a sulfonylurea less dependent on CYP2C9 for the duration of the antifungal.

Explanation

Fluconazole (and other azoles) inhibits CYP2C9, reducing phenytoin metabolism and increasing its plasma concentrations. QUADRO 2 of Annex 7 records this interaction in the azole antifungal and phenytoin sections. The phenytoin rise can be clinically significant within the first days, with nystagmus, ataxia and sedation. The risk is higher with high fluconazole doses, the elderly or hepatic impairment. Monitor phenytoin levels and reduce the phenytoin dose if needed; consider azoles with less inhibition (e.g. amphotericin) and reinforce clinical surveillance.

Explanation

Fluconazole moderately inhibits CYP3A4, one of the metabolic pathways for methadone (responsible for ~20% of metabolism). The effect is less pronounced than with ritonavir or ketoconazole, but clinically significant. Methadone levels may increase 1.5-2-fold, especially in CYP2D6 poor metabolisers who depend more on CYP3A4. Monitoring should include sedation, respiratory rate, and ECG (QTc). The effect is more pronounced with high fluconazole doses (>200 mg/day) and prolonged treatments.

Explanation

Explanation

Explanation

Duloxetine is metabolised by CYP1A2 and CYP2C19. Fluconazole is a potent CYP2C19 inhibitor. Co-administration may increase duloxetine levels 2-3-fold. Both drugs have hepatotoxic potential, and the combination increases the risk. Monitor liver function (AST/ALT) and serotonergic signs. Reduce duloxetine dose by 50% or switch to venlafaxine (less dependent on CYP2C19).

Explanation

Olanzapine is mainly metabolised by CYP1A2 and UGT. Fluconazole weakly inhibits CYP1A2. The effect on olanzapine levels is generally minimal (<20%). No routine dose adjustment required. Monitor for extrapyramidal effects if the patient is sensitive.