INN monograph
Posaconazole
Azole Antifungal [EPC] · POM
Verified · Updated 01 Aug 2026 · Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Professional class pharmacology (Antifungal)
Kenya market
Wholesale / list prices where loaded
Risk first
Contraindications
- 4 CONTRAINDICATIONS Known hypersensitivity to posaconazole or other azole antifungal agents.
- ( 4.1 ) Coadministration of posaconazole with the following drugs is contraindicated
- posaconazole increases concentrations and toxicities of: Sirolimus ( 4.2 , 5.1 , 7.1 ) CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes (TdP) ( 4.3 , 5.2 , 7.2 ) HMG-CoA Reductase Inhibitors Primarily Metabolized through CYP3A4 ( 4.4 , 7.3 ) Ergot alkaloids ( 4.5 , 7.4 ) Venetoclax: In patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) at initiation and during the ramp-up phase ( 4.6 , 5.11 , 7.16 ) 4.1 Hypersensitivity Posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. 4.2 Use with Sirolimus Posaconazole is contraindicated with sirolimus.
- Concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [ see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. 4.3 QT Prolongation with Concomitant Use with CYP3A4 Substrates Posaconazole is contraindicated with CYP3A4 substrates that prolong the QT interval.
- Concomitant administration of posaconazole with the CYP3A4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes [ see Warnings and Precautions (5.2) and Drug Interactions (7.2) ]. 4.4 HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4 Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [ see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ]. 4.5 Use with Ergot Alkaloids Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [ see Drug Interactions (7.4) ]. 4.6 Use with Venetoclax Coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) due to the potential for increased risk of tumor lysis syndrome [ see Warnings and Precautions (5.11) and Drug Interactions (7.16) ].
Precautions
- 5 WARNINGS AND PRECAUTIONS Calcineurin-Inhibitor Toxicity : Posaconazole increases concentrations of cyclosporine or tacrolimus
- reduce dose of cyclosporine and tacrolimus and monitor concentrations frequently.
- ( 5.1 ) Arrhythmias and QTc Prolongation : Posaconazole has been shown to prolong the QTc interval and cause cases of TdP.
- Administer with caution to patients with potentially proarrhythmic conditions.
- Do not administer with drugs known to prolong QTc interval and metabolized through CYP3A4.
- ( 5.2 ) Electrolyte Disturbances : Monitor and correct, especially those involving potassium (K + ), magnesium (Mg ++ ), and calcium (Ca ++ ), before and during posaconazole therapy.
- ( 5.3 ) Pseudoaldosteronism : Manifested by the onset or worsening of hypertension, and abnormal laboratory findings.
- Monitor blood pressure and potassium levels, and manage as necessary.
- ( 5.4 ) Hepatic Toxicity : Elevations in liver tests may occur.
- Discontinuation should be considered in patients who develop abnormal liver tests or monitor liver tests during treatment.
- ( 5.5 ) Concomitant Use with Midazolam : Posaconazole can prolong hypnotic/sedative effects.
- Monitor patients and benzodiazepine receptor antagonists should be available.
Point of care
Dosing
Adult
® oral suspension is not substitutable with posaconazole delayed-release tablets or Noxafil ® PowderMix for delayed-release oral suspension due to the differences in the dosing of each formulation. Therefore, follow the specific dosage recommendations for each of the formulations. ( 2.1 , 2.2 , 2.3 ) Administer posaconazole delayed-release tablets with or without food. ( 2.1 ) Table 1: Recommended Dosage in Adult Patients Indication Dosage Form, Dose, and Duration of Therapy Prophylaxis of invasive Aspergillus and Candida infections Delayed-Release Tablets: Loading dose: 300 mg (three 100 mg delayed-release tablets) twice a day on the first day. Maintenance dose: 300 mg (three 100 mg delayed-release tablets) once a day, starting on the second day. Duration of therapy is based on recovery from neutropenia or immunosuppression. ( 2.2 , 2.3 ) For pediatric patients, see the Full Prescribing Information for dosing recommendations for posaconazole delayed-release tablets ( 1.2 , 2.1 , 2.3 ) 2.1 Important Administration Instructions Non-substitutable Noxafil ® oral suspension is not substitutable with posaconazole delayed-release tablets or Noxafil ® PowderMix for delayed-release oral suspension due to the differences in the dosing of each formulation.Therefore, follow the specific dosage recommendations for each of the formulations [see Dosage and Administration (2.2, 2.3 )]. Posaconazole delayed-release tablets Swallow tablets whole. Do not divide, crush, or chew. Administer with or without food [ see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ]. For patients who cannot eat a full meal, posaconazole delayed-release tablets should be used instead of Noxafil ® oral suspension for the prophylaxis indication. Posaconazole delayed-release tablets generally provide higher plasma drug exposures than Noxafil ® oral suspension under both fed and fasted conditions, and therefore is the preferred oral formulation for the prophylaxis indication. 2.2 Dosing Regimen in Adult Patients Table 1: Dosing Regimens in Adult Patients Indication D ose and Frequency D uration of Therapy Prophylaxis of invasive Aspergillus and Cand ida infections Load ingdose : 300 mg (three 100 mg delayed-release tablets) twice a day on the first day. Maintenance dose : 300 mg (three 100 mg delayed-release tablets) once a day, starting on the second day. Load ingdose : 1 day Maintenance dose : Duration of therapy is based on recovery from neutropenia or immunosuppression. 2.3 Dosing Regimen in Pediatric Patients (ages 2 to less than 18 years of age) The recommended dosing regimen of posaconazole for pediatric patients 2 to less than 18 years of age is shown in Tables 2 [ see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ]. Table 2: Posaconazole Delayed-Release Tablet Dosing Regimens for Pediatric Patients (ages 2 to less than 18 years of age) Rec ommended Pediatric Dosage and Formulation Indication Weight/Age Delayed-Release Tablet D uration of therapy Prophylaxis of invasive A spergillus and Candida infections Less than or equal to 40 kg (2 to less than 18 years of age) Greater than 40 kg (2 to less than 18 years of age) Not Applicable Load ing dose: 300 mg twice daily on the first day Maintenance dose: 300 mg once daily Duration of therapy is based on recovery from neutropenia or immunosuppression. 2.5 Administration Instructions for Posaconazole Delayed-Release Tablets Swallow tablets whole. Do not divide, crush, or chew. Administer posaconazole delayed-release tablets with or without food [see Clinical Pharmacology (12.3) ]. 2.7 Non-substitutability between Noxafil ® Oral Suspension and Other Formulations Noxafil ® oral suspension is not substitutable with posaconazole delayed-release tablets or Noxafil ® PowderMix for delayed-release oral suspension due to the differences in the dosing of each formulation. Therefore, follow the specific dosage recommendations for each of the formulations [see Dosage and Administration (2.2 , 2.3) ]. 2.9 Dosage Adjustments in Patients with Renal Impairment The pharmacokinetics of posaconazole delayed-release tablets are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment.
Paediatric
8.4 Pediatric Use The safety and effectiveness of posaconazole delayed-release tablets for the prophylaxis of invasive Aspergillus and Candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy. Use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [ see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14) ]. The safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age.
Renal
Fluconazole dose-adjust in CKD; amphotericin nephrotoxicity high-alert.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic
Monitor LFTs for courses >14 days or higher-risk patients.
Safety
Drug interactions
- Match agent to site and species.
- For tinea, continue topical beyond clearance.
- Invasive fungal disease needs ID/specialist input and source control.
Safety
Adverse effects
- 6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling: Hypersensitivity [ see Contraindications (4.1) ] Arrhythmias and QT Prolongation [ see Warnings and Precautions (5.2) ] Hepatic Toxicity [ see Warnings and Precautions (5.5) ] Adult Patients: Common adverse reactions in studies with posaconazole in adults are diarrhea, nausea, fever, vomiting, headache, coughing, and hypokalemia.
- ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of posaconazole cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Clinical Trial Experience in Adults Clinical Trial Experience with Posaconazole Delayed-Release Tablets for Prophylaxis The safety of posaconazole delayed-release tablets has been assessed in 230 patients in clinical trials.
- Patients were enrolled in a non-comparative pharmacokinetic and safety trial of posaconazole delayed-release tablets when given as antifungal prophylaxis (Posaconazole Delayed-Release Tablet Study).
- Patients were immunocompromised with underlying conditions including hematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT.
- This patient population was 62% male, had a mean age of 51 years (range 19 to 78 years, 17% of patients were ≥65 years of age), and were 93% white and 16% Hispanic.
- Posaconazole therapy was given for a median duration of 28 days.
- Twenty patients received 200 mg daily dose and 210 patients received 300 mg daily dose (following twice daily dosing on Day 1 in each cohort).
- Table 9 presents adverse reactions observed in patients treated with 300 mg daily dose at an incidence of ≥10% in Posaconazole Delayed-Release Tablet Study.
- Table 9: Posaconazole Delayed-Release Tablet Study: Adverse Reactions in at Least 10% of Subjects Treated with 300 mg Daily Dose B ody System Posaconazole delayed-release tablet (300 mg) n=210 (%) Subjects Reporting any Adverse Reaction 207 (99) Blood and Lymphatic System Disorder Anemia 22 (10) Thrombocytopenia 29 (14) Ga s trointestinal Disorders Abdominal Pain 23 (11) Constipation 20 (10) Diarrhea 61 (29) Nausea 56 (27) Vomiting 28 (13) Genera l Disorders and Administration Site Conditions Asthenia 20 (10) Chills 22 (10) Mucosal Inflammation 29 (14) Edema Peripheral 33 (16) Pyrexia 59 (28) Metabolism and Nutrition Disorders Hypokalemia 46 (22) Hypomagnesemia 20 (10) Ner v ou s System Disorders Headache 30 (14) Re s p iratory, Thoracic and Mediastinal Disorders Cough 35 (17) Epistaxis 30 (14) Skin and Subcutaneous Tissue Disorders Rash 34 (16) Vascular Disorders Hypertension 23 (11) The most frequently reported adverse reactions (>25%) with posaconazole delayed-release tablets 300 mg once daily were diarrhea, pyrexia, and nausea.
- The most common adverse reaction leading to discontinuation of posaconazole delayed-release tablets 300 mg once daily was nausea (2%). 6.2 Postmarketing Experience The following adverse reaction has been identified during the post-approval use of posaconazole.
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.
- Endocrine Disorders : Pseudoaldosteronism
Use
Indications
1 INDICATIONS AND USAGE Posaconazole is an azole antifungal indicated as follows: Posaconazole is indicated for the prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy as follows: ( 1.2 ) o Posaconazole delayed-release tablets: adults and pediatric patients 2 years of age and older who weigh greater than 40 kg 1.2 Prophylaxis of Invasive Aspergillus and Candida Infections Posaconazole delayed-release tablets are indicated for the prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see Clinical Studies (14.2) ] as follows: Posaconazole delayed-release tablets: adults and pediatric patients 2 years of age and older who weigh greater than 40 kg
Pharmacology
Mode of action
It binds to fungal cell membranes with the resultant change in membrane permeability allowing leakage of intracellular components and cell death.
Full mechanism text
It binds to fungal cell membranes with the resultant change in membrane permeability allowing leakage of intracellular components and cell death. Azoles inhibit fungal CYP51 (lanosterol 14α-demethylase), depleting ergosterol and disrupting membrane integrity. Terbinafine inhibits squalene epoxidase. Polyenes bind ergosterol creating membrane pores. Echinocandins inhibit β-glucan synthase (cell wall).
ADME
Pharmacokinetics & PD
| Onset | Days for clinical response (varies) |
|---|---|
| Duration | Days–weeks per indication |
| Route | ORAL / TOPICAL / IV |
| Absorption | When given orally in healthy volunteers, posaconazole delayed-release tablets are absorbed with a median T max of 4 to 5 hours. Steady-state plasma concentrations are attained by Day 6 at the 300 mg dose (once daily after twice daily loading dose at Day 1). The absolute bioavaila... |
| Distribution | The mean volume of distribution of posaconazole after intravenous solution administration was 261 L and ranged from 226 to 295 L between studies and dose levels. Posaconazole is highly bound to human plasma proteins (>98%), predominantly to albumin. |
| Metabolism | Posaconazole primarily circulates as the parent compound in plasma. Of the circulating metabolites, the majority are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). Posaconazole does not have any major circulating oxidative (CYP450 mediated) metabolites.... |
| Elimination | Following administration of Noxafil oral suspension, posaconazole is predominantly eliminated in the feces (71% of the radiolabeled dose up to 120 hours) with the major com |
| Half-life | of midazolam was increased from 3 hours to 7 to 11 hours during coadministration with posaconazole. Additional clinical studies demonstrated that no clinically significant effects on zidovudine, lamivudine, indinavir, or caffeine were observed when administered with posaconazole... |
Full PK/PD text
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Posaconazole is an azole antifungal agent [ see Clinical Pharmacology (12.4) ]. 12.2 Pharmacodynamics Exposure Response Relationship Prophylaxis: In clinical studies of neutropenic patients who were receiving cytotoxic chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) or hematopoietic stem cell transplant (HSCT) recipients with Graft versus Host Disease (GVHD), a wide range of plasma exposures to posaconazole was noted following administration of Noxafil ® oral suspension. A pharmacokinetic-pharmacodynamic analysis of patient data revealed an apparent association between average posaconazole concentrations (C avg ) and prophylactic efficacy (Table 17). A lower Cavg may be associated with an increased risk of treatment failure, defined as treatment discontinuation, use of empiric systemic antifungal therapy (SAF), or occurrence of breakthrough invasive fungal infections. Table 17: Noxafil ® Oral Suspension Exposure Analysis (C avg ) in Prophylaxis Trials Prophylaxis in AML/MDS* Prophylaxis in GVHD † Cavg Range (ng/mL) Treatment Failure ‡ (%) Cavg Range (ng/mL) Treatment Failure‡ (%) Quartile 1 90-322 54.7 22-557 44.4 Quartile 2 322-490 37.0 557-915 20.6 Quartile 3 490-734 46.8 915-1563 17.5 Quartile 4 734-2200 27.8 1563-3650 17.5 Cavg = the average posaconazole concentration when measured at steady state * Neutropenic patients who were receiving cytotoxic chemotherapy for AML or MDS † HSCT recipients with GVHD ‡ Defined as treatment discontinuation, use of empiric systemic antifungal therapy (SAF), or occurrence of breakthrough invasive fungal infections 12.3 Pharmacokinetics General Pharmacokinetic Characteristics Posaconazole delayed-release tablets exhibit dose proportional pharmacokinetics after single and multiple dosing up to 300 mg. The mean pharmacokinetic parameters of posaconazole at steady state following administration of posaconazole delayed-release tablets 300 mg twice daily on Day 1, then 300 mg once daily thereafter in healthy volunteers and in neutropenic patients who are receiving cytotoxic chemotherapy for AML or MDS or HSCT recipients with GVHD are shown in Table 20. Table 20: Arithmetic Mean (%CV) of Steady State PK Parameters in Healthy Volunteers and Patients Following Administration of Posaconazole Delayed-Release Tablets (300 mg) * N AUC 0-24 hr (ng·hr/mL) Cav † (ng/mL) C max (ng/mL) C min (ng/mL) T max ‡ (hr ) t 1/2 (hr) CL/F (L/hr) Healthy Volunteers 12 51618 (25) 2151 (25) 2764 (21) 1785 (29) 4 (3-6) 31 (40) 7.5 (26) Patients 50 37900 (42) 1580 (42) 2090 (38) 1310 (50) 4 (1.3-8.3) - 9.39 (45) CV = coefficient of variation expressed as a percentage (%CV); AUC 0-T = Area under the plasma concentration-time curve from time zero to 24 hr; C max = maximum observed concentration; C min = minimum observed plasma concentration; T max = time of maximum observed concentration; t ½ = terminal phase half-life; CL/F = Apparent total body clearance * 300 mg twice daily on Day 1, then 300 mg once daily thereafter † Cav = time-averaged concentrations (i.e., AUC 0-24 hr/ 24hr) ‡ Median (minimum-maximum) Absorption: When given orally in healthy volunteers, posaconazole delayed-release tablets are absorbed with a median T max of 4 to 5 hours. Steady-state plasma concentrations are attained by Day 6 at the 300 mg dose (once daily after twice daily loading dose at Day 1). The absolute bioavailability of the oral delayed-release tablet is approximately 54% under fasted conditions. The C max and AUC of posaconazole following administration of posaconazole delayed-release tablets are increased 16% and 51%, respectively, when given with a high fat meal compared to a fasted state (see Table 22 ). Table 22: Statistical Comparison of Plasma Pharmacokinetics of Posaconazole Following Single Oral Dose Administration of 300 mg Posaconazole Delayed-Release Tablet to Healthy Subjects under Fasting and Fed Conditions Fasting Conditions Fed Conditions (High Fat Meal)* Fed/Fasting Pharmacokinetic Parameter N Mean (%CV) N Mean (%CV) GMR (90% CI) C max (ng/mL) 14 935 (34) 16 1060 (25) 1.16 (0.96, 1.41) AUC 0-72hr (hr∙ng/mL) 14 26200 (28) 16 38400 (18) 1.51 (1.33, 1.72) T max † (hr) 14 5.00 (3.00, 8.00) 16 6.00 (5.00, 24.00) N/A GMR=Geometric least-squares mean ratio; CI=Confidence interval * 48.5 g fat † Median (Min, Max) reported for T max Concomitant administration of posaconazole delayed-release tablets with drugs affecting gastric pH or gastric motility did not demonstrate any significant effects on posaconazole pharmacokinetic exposure (see Table 23 ). Table 23: The Effect of Concomitant Medications that Affect the Gastric pH and Gastric Motility on the Pharmacokinetics of Posaconazole Delayed-Release Tablets in Healthy Volunteers Coadministered Drug Administration Arms Change in C max (ratio estimate * ; 90% CI of the ratio estimate) Change in AUC 0-last (ratio estimate * ; 90% CI of the ratio estimate) Mylanta ® Ultimate strength liquid (Increase in gastric pH) 25.4 mEq/5 mL, 20 mL ↑6% (1.06; 0.90 -1.26)↑ ↑4% (1.04; 0.90 -1.20) Ranitidine (Zantac ® ) (Alteration in gastric pH) 150 mg (morning dose of 150 mg Ranitidine twice daily) ↑4% (1.04; 0.88 -1.23)↑ ¯3% (0.97; 0.84 -1.12) Esomeprazole (Nexium ® ) (Increase in gastric pH) 40 mg (every morning for 5 days, Day -4 to 1) ↑2% (1.02; 0.88-1.17)↑ ↑5% (1.05; 0.89 -1.24) Metoclopramide (Reglan ® ) (Increase in gastric motility) 15 mg four times daily for 2 days (Day -1 and 1) ¯14% (0.86, 0.73,1.02) ¯7% (0.93, 0.803,1.07) * Ratio Estimate is the ratio of coadministered drug plus posaconazole to posaconazole alone for C max or AUC 0-last . Distribution: The mean volume of distribution of posaconazole after intravenous solution administration was 261 L and ranged from 226 to 295 L between studies and dose levels. Posaconazole is highly bound to human plasma proteins (>98%), predominantly to albumin. Metabolism: Posaconazole primarily circulates as the parent compound in plasma. Of the circulating metabolites, the majority are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). Posaconazole does not have any major circulating oxidative (CYP450 mediated) metabolites. The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose. Posaconazole is primarily metabolized via UDP glucuronidation (phase 2 enzymes) and is a substrate for p-glycoprotein (P-gp) efflux. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. A summary of drugs studied clinically with the oral suspension or an early tablet formulation, which affect posaconazole concentrations, is provided in Table 27 . Table 27: Summary of the Effect of Coadministered Drugs on Posaconazole in Healthy Volunteers Coadministered Drug (Postulated Mechanism of Interaction) Coadministered Drug Dose/Schedule Posaconazole Dose/Schedule Effect on Bioavailability of Posaconazole Change in Mean C max (ratio estimate*; 90% CI of the ratio estimate) Change in Mean AUC (ratio estimate*; 90% CI of the ratio estimate) Efavirenz (UDP-G Induction) 400 mg once daily × 10 and 20 days 400 mg (oral suspension) twice daily × 10 and 20 days ¯45% (0.55; 0.47-0.66) ¯50% (0.50; 0.43-0.60) Fosamprenavir (unknown mechanism) 700 mg twice daily x 10 days 200 mg once daily on the 1 st day, 200 mg twice daily on the 2 nd day, then 400 mg twice daily x 8 Days ¯21% 0.79 (0.71-0.89) ¯23% 0.77 (0.68-0.87) Rifabutin (UDP-G Induction) 300 mg once daily x 17 days 200 mg (tablets) once daily × 10 days † ¯43% (0.57; 0.43-0.75) ¯49% (0.51; 0.37-0.71) Phenytoin (UDP-G Induction) 200 mg once daily x 10 days 200 mg (tablets) once daily × 10 days † ¯41% (0.59; 0.44-0.79) ¯50% (0.50; 0.36-0.71) * Ratio Estimate is the ratio of coadministered drug plus posaconazole to posaconazole alone for C max or AUC. † The tablet refers to a non-commercial tablet formulation without polymer. In vitro studies with human hepatic microsomes and clinical studies indicate that posaconazole is an inhibitor primarily of CYP3A4. A clinical study in healthy volunteers also indicates that posaconazole is a strong CYP3A4 inhibitor as evidenced by a >5-fold increase in midazolam AUC. Therefore, plasma concentrations of drugs predominantly metabolized by CYP3A4 may be increased by posaconazole. A summary of the drugs studied clinically, for which plasma concentrations were affected by posaconazole, is provided in Table 28 [ see Contraindications (4) and Drug Interactions (7.1) including recommendations]. Table 28: Summary of the Effect of Posaconazole on Coadministered Drugs in Healthy Adult Volunteers and Patients Coadministered Drug (Postulated Mechanism of Interaction is Inhibition of CYP3A4 by posaconazole) Coadministered Drug Dose/Schedule Posaconazole Dose/ Schedule Effect on Bioavailability of Coadministered Drugs Change in Mean C max (ratio estimate*; 90% CI of the ratio estimate) Change in Mean AUC (ratio estimate*; 90% CI of the ratio estimate) Sirolimus 2-mg single oral dose 400 mg (oral suspension) twice daily x 16 days ↑ 572% (6.72; 5.62-8.03) ↑ 788% (8.88; 7.26-10.9) Cyclosporine Stable maintenance dose in heart transplant recipients 200 mg (tablets) once daily x 10 days † ↑cyclosporine whole blood trough concentrations Cyclosporine dose reductions of up to 29% were required Tacrolimus 0.05-mg/kg single oral dose 400 mg (oral suspension) twice daily × 7 days ↑ 121% (2.21; 2.01-2.42) ↑ 358% (4.58; 4.03-5.19) Simvastatin 40-mg single oral dose 100 mg (oral suspension) once daily x 13 days Simvastatin Simvastatin ↑ 841% (9.41, 7.13-12.44) Simvastatin Acid ↑ 817% (9.17, 7.36-11.43) ↑ 931% (10.31, 8.40-12.67) Simvastatin Acid ↑ 634% (7.34, 5.82-9.25) 200 mg (oral suspension) once daily x 13 days Simvastatin Simvastatin ↑ 1041% (11.41, 7.99-16.29) Simvastatin Acid ↑ 851% (9.51, 8.15-11.10) ↑ 960% (10.60, 8.63-13.02) Simvastatin Acid ↑ 748% (8.48, 7.04-10.23) Midazolam 0.4-mg single intravenous dose ‡ 200 mg (oral suspension) twice daily x 7 days ↑ 30% (1.3; 1.13-1.48) ↑ 362% (4.62; 4.02-5.3) 0.4-mg single intravenous dose ‡ 400 mg (oral suspension) twice daily x 7 days ↑ 62% (1.62; 1.41-1.86) ↑ 524% (6.24; 5.43-7.16) 2-mg single oral dose ‡ 200 mg (oral suspension) once daily x 7 days ↑ 169% (2.69; 2.46-2.93) ↑ 470% (5.70; 4.82-6.74) 2-mg single oral dose ‡ 400 mg (oral suspension) twice daily x 7 days ↑ 138% (2.38; 2.13-2.66) ↑ 397% (4.97; 4.46-5.54) Rifabutin 300 mg once daily x 17 days 200 mg (tablets) once daily × 10 days † ↑ 31% (1.31; 1.10-1.57) ↑ 72% (1.72;1.51-1.95) Phenytoin 200 mg once daily PO x 10 days 200 mg (tablets) once daily x 10 days † ↑ 16% (1.16; 0.85-1.57) ↑ 16% (1.16; 0.84-1.59) Ritonavir 100 mg once daily x 14 days 400 mg (oral suspension) twice daily x 7 days ↑ 49% (1.49; 1.04-2.15) ↑ 80% (1.8;1.39-2.31) Atazanavir 300 mg once daily x 14 days 400 mg (oral suspension) twice daily x 7 days ↑ 155% (2.55; 1.89-3.45) ↑ 268% (3.68; 2.89-4.70) Atazanavir/ ritonavir boosted regimen 300 mg/100 mg once daily x 14 days 400 mg (oral suspension) twice daily x 7 days ↑ 53% (1.53; 1.13-2.07) ↑ 146% (2.46; 1.93-3.13) * Ratio Estimate is the ratio of coadministered drug plus posaconazole to coadministered drug alone for C max or AUC. † The tablet refers to a non-commercial tablet formulation without polymer. ‡ The mean terminal half-life of midazolam was increased from 3 hours to 7 to 11 hours during coadministration with posaconazole. Additional clinical studies demonstrated that no clinically significant effects on zidovudine, lamivudine, indinavir, or caffeine were observed when administered with posaconazole 200 mg once daily; therefore, no dose adjustments are required for these coadministered drugs when coadministered with posaconazole 200 mg once daily. Excretion: Following administration of Noxafil oral suspension, posaconazole is predominantly eliminated in the feces (71% of the radiolabeled dose up to 120 hours) with the major com
Kenya
Brands & prices
| Brand | Company | Pack | KES |
|---|---|---|---|
| Noxafil | Merck Sharp & Dohme | Standard Commercial Pack | — |
Special populations
Pregnancy & lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. Available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. In pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. Doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see Data). Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (Gestational Days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). The no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. No malformations were seen in rabbits dosed during organogenesis (Gestational Days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). In the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. In rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen.
Lactation
: Based on animal data, may cause fetal harm. ( 8.1 ) Pediatrics : Safety and effectiveness in patients younger than 2 years of age have not been established. ( 8.4 ) Severe Renal Impairment : Monitor closely for breakthrough fungal infections. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. Available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. In pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. Doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see Data). Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (Gestational Days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). The no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. No malformations were seen in rabbits dosed during organogenesis (Gestational Days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). In the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. In rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. 8.2 Lactation Risk Summary There are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. Posaconazole is excreted in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of posaconazole delayed-release tablets for the prophylaxis of invasive Aspergillus and Candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy. Use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [ see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14) ]. The safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. 8.5 Geriatric Use No overall differences in the safety of posaconazole delayed-release tablets were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. No clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [ see Clinical Pharmacology (12.3) ]. Of the 230 patients treated with posaconazole delayed-release tablets , 38 (17%) were greater than 65 years of age. No overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Renal Impairment Following single-dose administration of 400 mg of the Noxafil ® oral suspension, there was no significant effect of mild (eGFR: 50-80 mL/min/1.73 m 2 , n=6) or moderate (eGFR: 20 to 49 mL/min/1.73 m 2 , n=6) renal impairment on posaconazole pharmacokinetics; therefore, no dose adjustment is required in patients with mild to moderate renal impairment. In subjects with severe renal impairment (eGFR: <20 mL/min/1.73 m 2 ), the mean plasma exposure (AUC) was similar to that in patients with normal renal function (eGFR: >80 mL/min/1.73 m 2 ); however, the range of the AUC estimates was highly variable (CV=96%) in these subjects with severe renal impairment as compared to that in the other renal impairment groups (CV<40%). Due to the variability in exposure, patients with severe renal impairment should be monitored closely for breakthrough fungal infections [ see Dosage and Administration (2.9) ]. Similar recommendations apply to posaconazole delayed-release tablets; however, a specific study has not been conducted with the posaconazole delayed-release tablets. 8.7 Hepatic Impairment After a single oral dose of Noxafil ® oral suspension 400 mg, the mean AUC was 43%, 27%, and 21% higher in subjects with mild (Child-Pugh Class A, N=6), moderate (Child-Pugh Class B, N=6), or severe (Child-Pugh Class C, N=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (N=18). Compared to subjects with normal hepatic function, the mean C max was 1% higher, 40% higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. The mean apparent oral clearance (CL/F) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. The elimination half-life (t½) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively. It is recommended that no dose adjustment of posaconazole delayed-release tablets is needed in patients with mild to severe hepatic impairment (Child-Pugh Class A, B, or C) [see Dosage and Administration (2) and Warnings and Precautions (5.4) ]. However, a specific study has not been conducted with delayed-release tablets. 8.8 Gender The pharmacokinetics of posaconazole are comparable in males and females. No adjustment in the dosage of posaconazole is necessary based on gender. 8.9 Race The pharmacokinetic profile of posaconazole is not significantly affected by race. No adjustment in the dosage of posaconazole is necessary based on race. 8.10 Weight Pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. It is, therefore, suggested to closely monitor for breakthrough fungal infections.
Diet
Food & alcohol
- Drug & food interactions (label) 7 DRUG INTERACTIONS Posaconazole is primarily metabolized via UDP glucuronosyltransferase and is a substrate of p-glycoprotein (P-gp) efflux. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. Coadministration of drugs that can decrease the plasma concentrations of posaconazole should generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections. Posaconazole is also a strong inhibitor of CYP3A4. Therefore, plasma concentrations of drugs predominantly metabolized by CYP3A4 may be increased by posaconazole [ see Clinical Pharmacology (12.3) ]. The following information was derived from data with Noxafil ® oral suspension or early tablet formulation unless otherwise noted. All drug interactions with Noxafil ® oral suspension, except for those that affect the absorption of posaconazole (via gastric pH and motility), are considered relevant to posaconazole delayed-release tablet as well [see Drug Interactions (7.9) and (7.13) ]. Interaction Drug Interaction Rifabutin, phenytoin, efavirenz, cimetidine, esomeprazole* Avoid coadministration unless the benefit outweighs the risks ( 7.6 , 7.7 , 7.8 , 7.9 ) Other drugs metabolized by CYP3A4 Consider dosage adjustment and monitor for adverse effects and toxicity ( 7.1 , 7.10 , 7.11 ) Digoxin Monitor digoxin plasma concentrations ( 7.12 ) Fosamprenavir, metoclopramide* Monitor for breakthrough fungal infections ( 7.6 , 7.13 ) *The drug interactions with esomeprazole and metoclopramide do not apply to posaconazole tablets. 7.1 Immunosuppressants Metabolized by CYP3A4 Sirolimus: Concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity. Therefore, posaconazole is contraindicated with sirolimus [ see Contraindications (4.2) and Clinical Pharmacology (12.3) ]. Tacrolimus: Posaconazole has been shown to significantly increase the C max and AUC of tacrolimus. At initiation of posaconazole treatment, reduce the tacrolimus dose to approximately one-third of the original dose. Frequent monitoring of tacrolimus whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus dose adjusted accordingly [ see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ]. Cyclosporine: Posaconazole has been shown to increase cyclosporine whole blood concentrations in heart transplant patients upon initiation of posaconazole treatment. It is recommended to reduce cyclosporine dose to approximately three-fourths of the original dose upon initiation of posaconazole treatment. Frequent monitoring of cyclosporine whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the cyclosporine dose adjusted accordingly [ see Warnings and Precautions (5.
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Sources & disclaimer
Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Professional class pharmacology (Antifungal)
Last reviewed: 01 Aug 2026
Decision support only — not a substitute for clinical judgment, product SmPC, or Kenya STG/EML.