Version June 2024
| Available preparations | Oral bioavailability | Metabolism and clearance | Enzyme/ transporter inhibition* | Protein binding | Half-life in adults (hours) | Availability of therapeutic drug monitoring¶ | |
| Fluconazole | Tablet Oral solution IV solution | >90% (unaltered by food or elevated gastric pH) | Renally as unchanged drug (80%) requiring dose adjustment in renal impairment: Hepatic metabolism (11%) | CYPs 2C19 (strong), 2C9 (moderate), 3A4 (moderate, more consistently observed with fluconazole ≥200 mg/day) | 11 to 12% | Approximately 24; prolonged in renal impairment | No |
| Isavuconazole (formulated as prodrug isavuconazonium sulfate) | Capsule IV solution | 98% (unaltered by food or elevated gastric pH) | Hepatically by CYP3A4 and UGT glucuronidation | CYP3A4 (moderate), P-gp efflux (weak to moderate) | >99% | 130 | No |
| Itraconazole | CapsuleΔ TabletΔ Oral solutionΔ SUBA capsuleΔ IV solution◊ (not available in United States) | Oral capsule and tablet: approximately 55% (with food and acidic beverage); drugs that elevate gastric pH (PPI, H2 antagonists) decrease absorption of capsule Oral solution: approximately 75% (without food) SUBA capsule: 173% (relative to traditional capsules) | Hepatically by CYP3A4 to active metabolites | CYP3A4 (strong), P-gp efflux | 99% | 25 to 50 | Yes Target trough ≥1 mcg/mL by HPLC or ≥3 mcg/mL by bioassay |
| Posaconazole | Tablet (delayed release) Oral suspension IV solution◊ | Tablet (delayed release): 54% (preferably with some food) Oral suspension: variable (optimally absorbed with a high-fat meal in divided doses; however, absorption may be sufficient with any type of meal, a nutritional supplement, or an acidic beverage) | Minimally metabolized; most drug (66%) is cleared unchanged in feces; approximately 17% undergoes hepatic UGT glucuronidation | CYP3A4 (strong) P-gp efflux | >98% | Tablets: 26 to 31 Suspension: approximately 35 (range 20 to 66) Intravenous: approximately 27 | Yes Prophylaxis: target trough ≥0.7 mcg/mL Treatment: target trough ≥1 mcg/mL |
| Voriconazole | Tablet Oral suspension IV solution◊ | >90% (tablet and oral suspension, taken without food); absorption is decreased ≥30% when taken with food | Hepatically by CYPs 2C19 (major)§, 2C9, and 3A4 | CYP2C19 (moderate), 3A4 (strong) | 58% | Variable¥; dependent upon dose, serum concentration, and patient-specific characteristics (eg, CYP2C19 polymorphism) | Yes¥ Target trough 1 to 5.5 mcg/mL |
CYP: cytochrome P450 metabolism; HPLC: high-performance liquid chromatography; IV: intravenous; P-gp: P-glycoprotein efflux transporters; PPI: proton pump inhibitor; UGT: uridine 5'-diphospho-glucuronosyltransferase glucuronidation (ie, phase II [non-CYP] hepatic metabolism).
* The classification of azole antifungal effects on drug metabolism are based upon US Food and Drug Administration guidance. Other sources may use a different classification system resulting in some agents being classified differently. Weak inhibitor effects are not listed. Clinically significant interactions can occasionally occur due to weak inhibitors, particularly if the target drug has a narrow therapeutic margin. Refer to the Lexicomp drug interactions program for a full list of potential interactions.
¶ Therapeutic targets listed are based on limited study data and should be regarded as only general guidance. Decisions about dose modification must always be made within the context of the clinical status of the patient as detailed in the UpToDate topic reviews.
Δ Itraconazole capsules and tablets are not bioequivalent to the oral solution and should not be interchanged on a milligram basis. Itraconazole SUBA capsules are also not bioequivalent to traditional capsules or tablets or to the oral solution.
◊ Intravenous solution contains a cyclodextrin vehicle that can accumulate in patients with renal impairment; refer to the topic review on the pharmacology of azoles for detailed recommendations.
§ CYP2C19 metabolism of voriconazole is highly polymorphic; serum concentrations may be elevated two- to fourfold in patients with low CYP2C19 expression (3 to 5% White population and African American population, 15 to 20% Asian population) relative to extensive metabolizers (ie, most patients).
¥ Voriconazole exhibits nonlinear pharmacokinetics and metabolism appears to be saturable; thus, alteration of serum concentrations observed following a dose change can be disproportional to the adjustment. For example, a 50% dose increase can lead to a 150% increase in serum concentration. Refer to the UpToDate topic review on the pharmacology of azoles for details.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
