Antifungal drugs. Remember to report any suspected adverse reactions. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. http://www.aidsinfo.nih.gov, 441. Simulated (red thick line, population mean; thin gray line, individual subject; black dotted lines, 5th and 95th percentile of population) and clinically reported (blue circles, 36 orange triangle, 54 … The Medicines and Healthcare products Regulatory Agency (MHRA) encourage anyone to voluntarily report ADRs (however minor) via the Yellow Card Scheme to gather more information and gain more understanding of a new medication. Updates may be available at IDSA website at www.idsociety.org. Courtney R, Pai S, Laughlin M et al. ), IV solution: Avoid using in patients with moderate or severe renal impairment (eGFR <50 mL/minute) unless potential benefits justify risks.1 The IV vehicle contained in the IV preparation (SBECD) is expected to accumulate in such patients.1 If IV posaconazole used in patients with moderate or severe renal impairment, closely monitor Scr;1 consider switching to oral posaconazole if Scr increases.1, GI effects (nausea,1 2 5 8 9 10 vomiting,1 2 5 8 9 10 diarrhea,1 2 8 9 10 abdominal pain,1 2 5 8 9 10 anorexia,1 9 constipation,1 dry mouth,38 dyspepsia,1 flatulence,1 5 9 decreased appetite1 ), fever,1 10 headache,1 2 5 8 9 10 38 increased sweating,1 rigors,1 chills,1 mucosal inflammation,1 dizziness,1 5 9 10 38 fatigue,1 8 9 edema (legs),1 asthenia,1 9 weakness,1 9 decreased weight,1 dehydration,1 hypertension,1 hypotension,1 11 vaginal hemorrhage,1 tachycardia,1 bacteremia,1 pneumonia,1 herpes simplex infection,1 cytomegalovirus infection,1 oral candidiasis,1 pharyngitis,1 musculoskeletal pain,1 arthralgia,1 back pain,1 petechiae,1 insomnia,1 9 coughing,1 9 dyspnea,1 epistaxis,1 rash,1 2 8 9 10 petechiae,1 pruritus.1 9 Also, anemia,1 neutropenia,1 5 9 11 thrombocytopenia,1 9 hypocalcemia,1 hypokalemia,1 hypomagnesemia,1 hyperglycemia,1 increased AST,1 2 8 increased ALT,1 2 8 increased γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP),1 increased alkaline phosphatase,1 9 bilirubinemia.1 11, Inhibits CYP3A4.1 2 5 Does not appear to inhibit CYP1A2, 2C8/9, 2D6, or 2E1.62, Principally metabolized via uridine diphosphate (UDP)-glucuronosyltransferase glucuronidation (UGT; phase 2 enzymes) and is a substrate of P-glycoprotein transport system.1 2, Potential pharmacokinetic interaction with drugs metabolized by CYP3A4 (increased plasma concentrations of CYP3A4 substrates).1 2 5 56, Risk of prolonged QT interval and torsades de pointes with CYP3A4 substrates that prolong the QTc.1 Concomitant use contraindicated.1 37 (See Contraindications under Cautions. Salvage therapy for invasive aspergillosis. Clin Infect Dis. 1. 2008; 46:327-60. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America. Wheat LJ, Connolly P, Smedema M et al. Evaluation of the pharmacokinetics of posaconazole and rifabutin following co-administration to healthy men. If you perform a search and subsequently filter by an Active … ), Posaconazole delayed-release tablets are labeled by FDA only for prophylaxis of invasive Aspergillus and Candida infections.1 Manufacturer states that the delayed-release tablets are the preferred preparation when oral posaconazole is used for such prophylaxis since the tablets generally provide higher posaconazole exposures than the oral suspension under both fed and fasting conditions.1 (See Plasma Concentrations under Pharmacokinetics. 81. Antimicrob Agents Chemother. Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. 2004; 23:1451-4. http://www.ncbi.nlm.nih.gov/pubmed/15607679?dopt=AbstractPlus, 20. Updates may be available at IDSA website at www.idsociety.org. ), Although there are some differences in posaconazole pharmacokinetics in individuals with hepatic impairment compared with those with normal hepatic function (see Absorption: Special Populations and also see Elimination under Pharmacokinetics),1 41 the manufacturer states that dosage adjustments are not considered necessary in patients with mild, moderate, or severe hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration. Pagano L, Valentini CG, Caira M et al. Our 2014 approach to mucormycosis. Effect of varying amounts of a liquid nutritional supplement on the pharmacokinetics of posaconazole in healthy volunteers. Am J Health Syst Pharm. Cumpston A, Caddell R, Shillingburg A et al. Safety and efficacy of posaconazole in the long-term treatment of azole-refractory oropharyngeal and esophageal candidiasis in patients with HIV infection. 2009; 66:225-36. http://www.ncbi.nlm.nih.gov/pubmed/19179636?dopt=AbstractPlus, 52. Antimicrob Agents Chemother. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. Posaconazole enhances the activity of amphotericin B against Aspergillus hyphae in vitro. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Freifeld AG, Bow EJ, Sepkowitz KA et al. Intelence (etravirine) tablets prescribing information. See Important Safety Information and … Common side effects of Noxafil include: cytomegalovirus disease, febrile neutropenia, herpes simplex infection, abdominal pain, anemia, arthralgia, back pain, constipation, cough, diarrhea, dizziness, dyspepsia, epistaxis, fatigue, fever, headache, hyperbilirubinemia, hyperglycemia, hypertension, hypokalemia, hypotension, insomnia, lower extremity edema, mucositis, musculoskeletal pain, nausea, neutropenia, petechia, pharyngitis, pruritus, rigors, skin rash, tachycardia, thrombocytopenia, vaginal he… Curr Med Res Opin. 37. Panel on Clinical Practices for Treatment of HIV Infection of the Department of Health and Human Services (DHHS). 32. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. 2011; 52:427-31. 425. After a new medicine (or vaccine) has been brought to the market there is still a lot that can be learned about the drug from its widespread use. Arikan S, Sancak B, Alp S et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. New medicines and vaccines that are under additional monitoring have an inverted black triangle symbol ( ) displayed in their package leaflet and summary of product characteristics, together with a short sentence explaining what the triangle means – it does not mean the medicine is unsafe. Updates may be available at the US Department of Health and Human Services HIV/AIDS Information Services (AIDSInfo) website. Noxafil 300 mg concentrate for solution for infusion -13/11/19: 13/11/19: Posaconazole : MSD Ireland (Human Health) Limited : Noxafil 40 mg/ml oral suspension -13/11/19: 13/11/19: Posaconazole : MSD Ireland (Human Health) Limited : Noxafil … 2007; 20:695-704. http://www.ncbi.nlm.nih.gov/pubmed/17934079?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2176050&blobtype=pdf, 60. Galina Lepesheva 54. Vazquez JA, Skiest DJ, Nieto L et al. Merck and Co. Inc. Noxafil (posaconazole) delayed-release tablets, oral suspension, and injection prescribing information. http://www.ncbi.nlm.nih.gov/pubmed/16206093?dopt=AbstractPlus, 428. Clin Pharmacol. Posaconazole salvage therapy allows successful allogeneic hematopoietic stem cell transplantation in patients with refractory invasive mold infections. Krishna G, Ma L, Vickery D et al. ), Shake oral suspension well prior to each dose.1 Oral suspension contains 40 mg of posaconazole per mL.1 Administer dose using the calibrated measuring spoon provided by the manufacturer designed to measure 2.5- and 5-mL doses.1 Rinse calibrated spoon with water after each dose and before storage.1, Must be swallowed whole;1 do not divide, crush, or chew.1, Administer with food to enhance oral absorption and optimize posaconazole plasma concentrations.1, Labeled by FDA only for prophylaxis of invasive Aspergillus and Candida infections in adults and children 13 years of age or older.1, FDA alerted healthcare professionals about risk of medication errors with oral preparations of posaconazole.75 Errors occurred when the wrong oral preparation was prescribed and/or dispensed without consideration for the different dosage and frequency of administration required for the other preparation.75 At least 1 fatality occurred in a patient who received incorrect dosage (underdosage) after being provided with posaconazole oral suspension (instead of the delayed-release tablets) without consideration for the dosage and frequency of administration required for the oral suspension.75 In other cases, clinicians switched patients from posaconazole oral suspension to the delayed-release tablets and the delayed-release tablets were prescribed and/or dispensed without adjusting dosage to that required for the delayed-release tablets.75 Adverse effects (e.g., nausea, vomiting, low serum potassium concentrations) reported in some of these patients, possibly as the result of the incorrect dosage and higher posaconazole exposures.75, Be aware that dosage recommendations for posaconazole oral suspension and posaconazole delayed-release tablets are not the same;1 75 follow dosage recommendations for the specific oral preparation.1 75 (See Dosage under Dosage and Administration. Posaconazole a novel triazole antifungal for the treatment of invasive fungal infections. Clin Infect Dis. Posaconazole tablet pharmacokinetics: lack of effect of concomitant medications altering gastric pH and gastric motility in healthy subjects. Raad II, Hachem RY, Herbrecht R et al. Wexler D, Courtney R, Richards W et al. 22. Intrapulmonary pharmacokinetics and pharmacodynamics of posaconazole at steady state in healthy subjects. Black triangles are naturally occurring spaces between teeth due to two triangular shaped teeth touching each other. Clin Microbiol Infect. Perit Dial Int. Whitehouse Station, NJ; 2015 Nov. 2. ), Potential pharmacokinetic interaction with drugs that are inhibitors or inducers of P-glycoprotein with possible increase or decrease in plasma posaconazole concentrations, respectively.1, Pharmacokinetic interactions likely with drugs that are inhibitors or inducers of uridine diphosphate-glucuronosyltransferase UDP glucuronidation (UGT; phase 2 enzymes) with possible increase or decrease in plasma posaconazole concentrations, respectively.1 5, In vitro evidence of synergism against Aspergillus hyphae and indifference against Aspergillus conidia14, In vitro evidence of indifference against Rhizopus oryzae; no evidence of synergism or antagonism66, No clinically important pharmacokinetic interactions1 60 91, Phenytoin: Decreased posaconazole peak plasma concentrations and AUC; increased phenytoin peak plasma concentration and AUC1 24 40, Phenytoin: Avoid concomitant use unless benefits outweigh risks;1 24 40 56 if concomitant use necessary, closely monitor for breakthrough fungal infections;1 also frequently monitor phenytoin concentrations and consider reducing phenytoin dosage1 40, Rifabutin: Decreased posaconazole peak plasma concentrations and AUC; increased rifabutin peak plasma concentrations and AUC;1 23 40 possible increased risk of rifabutin-associated adverse effects (e.g., uveitis, leukopenia)23, Rifabutin: Avoid concomitant use unless benefits outweigh risks;1 2 23 40 if used concomitantly, closely monitor for breakthrough fungal infections;1 also frequently monitor for rifabutin-associated adverse effects (e.g., uveitis, leukopenia) and frequently assess CBCs1 23 40, Ritonavir-boosted or unboosted atazanavir:1 44 200 Increased atazanavir concentrations200, Cobicistat-boosted atazanavir: Possible increased atazanavir concentrations200, Ritonavir-boosted, cobicistat-boosted, or unboosted atazanavir: Monitor frequently for atazanavir-associated adverse effects and toxicity1 44 200, Benzodiazepines (alprazolam, midazolam, triazolam), Midazolam: Substantially increased peak midazolam plasma concentrations, AUC, and mean terminal half-life;1 37 40 49 may potentiate and prolong midazolam hypnotic and sedative effects1, Other benzodiazepines metabolized by CYP3A4 (e.g., alprazolam, triazolam): Possible increased benzodiazepine plasma concentrations1 5 49, Midazolam and other benzodiazepines metabolized by CYP3A4 (e.g., alprazolam, triazolam): Monitor frequently for benzodiazepine adverse effects;1 40 49 benzodiazepine receptor antagonist must be available to reverse possible adverse effects1, No clinically important pharmacokinetic interactions1, Dosage adjustment not needed if used with posaconazole 200 mg daily1, Calcium-channel blocking agents (diltiazem, felodipine, nicardipine, nifedipine, verapamil), Calcium-channel blockers metabolized by CYP3A4 (e.g., diltiazem, felodipine, nicardipine, nifedipine, verapamil): Possible increased plasma concentrations of the calcium-channel blocker1, Monitor for adverse effects and toxicity associated with calcium-channel blockers;1 reduction of the calcium-channel blocker dosage may be needed1, Possible increased daclatasvir concentrations178, If used with posaconazole, use daclatasvir dosage of 30 mg once daily178, Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased posaconazole, darunavir, and ritonavir or cobicistat concentrations200, Ritonavir-boosted or cobicistat-boosted darunavir: Monitor for posaconazole-, darunavir-, and ritonavir- or cobicistat-associated adverse effects;200 237 consider monitoring posaconazole concentrations200, Decreased posaconazole peak plasma concentrations and AUC1 44 200, Avoid concomitant use unless benefits outweigh risks;1 44 200 if concomitant use is necessary, monitor plasma posaconazole concentrations and adjust dosage accordingly200, Elvitegravir used with a ritonavir-boosted HIV protease inhibitor: Possible increased elvitegravir concentrations200, Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir (EVG/c/FTC/TDF): Possible increased posaconazole, elvitegravir, and cobicistat concentrations200, EVG/c/FTC/TDF: Monitor posaconazole concentrations200, Ergot alkaloids (ergotamine, dihydroergotamine), Possible increased plasma concentrations of ergot alkaloids resulting in ergotism1, Possible increased etravirine plasma concentrations;200 214 no change in posaconazole concentrations214, Experts state dosage adjustment not needed;200 manufacturer of etravirine states posaconazole dosage adjustment may be needed depending on other concomitantly administered drugs214, Fosamprenavir: Decreased posaconazole concentrations1 200, Ritonavir-boosted fosamprenavir: Possible increased amprenavir (active metabolite of fosamprenavir) and posaconazole concentrations200, Fosamprenavir: Closely monitor for breakthrough fungal infections;1 monitor posaconazole concentrations200, Ritonavir-boosted fosamprenavir: Consider monitoring posaconazole concentrations;200 monitor for amprenavir-associated adverse effects200, No clinically important pharmacokinetic interactions;2 hypoglycemia reported2, Dosage adjustments not needed;1 monitor blood glucose concentrations1, Histamine H2-receptor antagonists (cimetidine, ranitidine), Cimetidine: Decreased posaconazole peak plasma concentrations and AUC if used with posaconazole oral suspension1 2 4 5 40, Other H2-receptor antagonists (e.g., ranitidine): No pharmacokinetic interactions reported with posaconazole oral suspension or delayed-release tablets1 91, Cimetidine: Avoid concomitant use with posaconazole oral suspension unless benefits outweigh risks;1 40 if concomitant use necessary, monitor closely for breakthrough fungal infections1, Other H2-receptor antagonists (e.g., ranitidine): Dosage adjustment not needed1 91, Simvastatin: Substantially increased simvastatin concentrations if used with posaconazole oral suspension;1 may lead to rhabdomyolysis1, Other statins metabolized by CYP3A4 (e.g., atorvastatin, lovastatin): Possible increased concentrations of the statin;1 may lead to rhabdomyolysis1, Atorvastatin, lovastatin, simvastatin: Concomitant use contraindicated1, Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus), Cyclosporine: Increased cyclosporine concentrations, but no change in posaconazole concentrations;1 22 increased cyclosporine concentrations associated with serious adverse effects (e.g., nephrotoxicity, leukoencephalopathy, death)1, Sirolimus: Substantially increased sirolimus peak plasma concentrations and AUC;1 40 possible sirolimus toxicity1, Tacrolimus: Increased tacrolimus peak concentrations and AUC1 22 40, Cyclosporine: Decrease cyclosporine dosage by 25% if initiating posaconazole;1 5 56 monitor cyclosporine trough concentrations frequently during and after discontinuing posaconazole and adjust cyclosporine dosage as needed1 2 4 5 22 37, Sirolimus: Concomitant use contraindicated1, Tacrolimus: Decrease tacrolimus dosage by 66% if initiating posaconazole;1 monitor tacrolimus trough concentrations frequently during and after discontinuing posaconazole and adjust tacrolimus dose as needed1 2 4 22 40, No clinically important pharmacokinetic interactions with posaconazole oral suspension1, Fixed combination of lopinavir and ritonavir (lopinavir/ritonavir): Possible increased lopinavir and posaconazole concentrations200, Lopinavir/ritonavir: Consider monitoring posaconazole concentrations;200 monitor for lopinavir-associated adverse effects200, Decreased posaconazole mean peak plasma concentrations and AUC if used with posaconazole oral suspension;1 no clinically important pharmacokinetic interactions if used with posaconazole delayed-release tablets1 91, Posaconazole oral suspension: Monitor closely for breakthrough fungal infections1, Posaconazole delayed-release tablets: Dosage adjustments not needed1, Possible pharmacokinetic interaction and potential for serious or life-threatening reactions (e.g., prolonged QT interval, torsades de pointes) 1, Proton-pump inhibitors (esomeprazole, omeprazole), Esomeprazole: Decreased posaconazole mean peak plasma concentrations and AUC if used with posaconazole oral suspension;1 no clinically important pharmacokinetic interaction if used with posaconazole delayed-release tablets1 91, Omeprazole: Decreased posaconazole trough concentrations if used with posaconazole oral suspension50, Esomeprazole: Monitor closely for breakthrough fungal infections if used with posaconazole oral suspension;1 dosage adjustments not necessary if used with posaconazole delayed-release tablets1, Omeprazole: Monitor posaconazole concentrations if used with posaconazole oral suspension or consider switching to another antifungal50 56, Possible increased rilpivirine concentrations200, Dosage adjustments not needed;200 monitor for breakthrough fungal infections200, Increased ritonavir peak plasma concentration and AUC1, Monitor frequently for ritonavir adverse effects and toxicity1, Ritonavir-boosted saquinavir: Possible increased saquinavir and posaconazole concentrations200, Ritonavir-boosted saquinavir: Consider monitoring posaconazole concentrations;200 monitor for saquinavir-associated adverse effects200, Possible substantially increased simeprevir concentrations187, Ritonavir-boosted tipranavir: Possible increased tipranavir and posaconazole concentrations200, Ritonavir-boosted tipranavir: Consider monitoring posaconazole concentrations;200 monitor for tipranavir-associated adverse effects200, Possible increased plasma concentrations of vinca alkaloids (e.g., vincristine, vinblastine);1 37 possible increased risk of neurotoxicity1, Monitor for manifestations of vinca alkaloid toxicity (neurotoxicity) and consider adjusting dosage of the vinca alkaloid1 37 56, Oral suspension: Dose-proportional increases in AUC when administered orally over a dosage range of 50 mg twice daily to 400 mg twice daily.1 In febrile neutropenic patients or those with refractory invasive fungal infections, no further increases in exposure if dosage increased from 400 mg twice daily to 600 mg twice daily.1, Delayed-release tablets: Dose-proportional pharmacokinetics following single and multiple doses up to 300 mg.1 Tablets contain posaconazole mixed with a pH-sensitive polymer (hypromellose acetate succinate) that enhances posaconazole oral bioavailability.88 91 The pH-sensitive polymer limits release of posaconazole in acidic pH of the stomach, allowing release in elevated pH environment of the intestines;88 91 may also inhibit recrystallization of posaconazole in intestinal fluid, resulting in a greater portion of the drug being available for absorption.88 91 Absolute bioavailability approximately 54% under fasting conditions.1, IV solution: Dose-proportional pharmacokinetics following IV infusion of single doses of 200–300 mg.1, Oral suspension: Median time to peak plasma posaconazole concentrations is approximately 3–8 hours after oral administration.1 15 61 71 72 73 Steady-state plasma concentrations achieved at 7–10 days.1, Delayed-release tablets: Median time to peak plasma posaconazole concentrations is approximately 4–5 hours after oral administration.1 Steady-state plasma concentrations achieved by day 6 with regimen of 300 mg twice daily on day 1 (loading dosage) followed by 300 mg once daily thereafter (maintenance dosage).1 Data from solid organ transplant recipients or patients with hematologic malignancies indicate consistently higher posaconazole plasma concentrations with delayed-release tablets (300 mg once daily; 300 mg twice daily on day 1 followed by 300 mg once daily) compared with the oral suspension (400 mg twice daily or 200 mg 3 or 4 times daily).89 90 91 92, IV solution: Median time to peak posaconazole plasma concentrations is 1.5 hours following IV infusion.1, Oral suspension given via NG tube†: In a crossover study in healthy adults who received a single 400-mg dose of posaconazole oral suspension orally or via an NG tube† after a liquid nutritional supplement (Boost Plus), mean time to peak plasma concentrations was similar (4 hours) but mean peak plasma concentrations and AUC were 19 and 23% lower, respectively, when the dose was administered via NG tube.1 39 In some patients, peak plasma concentrations and AUC were substantially reduced (up to approximately 50%) when the oral suspension was administered via an NG tube compared with oral administration.1 39, Food or a liquid nutritional supplement increases posaconazole plasma concentrations and AUC.1 15 60 71, Oral suspension: Following a single 200-mg dose with a nonfat or high-fat meal (approximately 50 g of fat), mean peak plasma posaconazole concentrations and AUC were both approximately threefold or fourfold higher, respectively, compared with administration in the fasted state.1 61, Oral suspension: In a crossover study in healthy adults who received a single 400-mg dose during or 20 minutes following a high-fat meal, mean peak plasma posaconazole concentrations and AUC were approximately threefold or fourfold higher, respectively, compared with administration in the fasted state.1 When the dose was administered 5 minutes prior to the high-fat meal, mean peak plasma posaconazole concentrations and AUC were similar to those observed when the drug is administered in the fasted state.1, Oral suspension: Following a single 400-mg dose of posaconazole given with 240 mL of liquid nutritional supplement (Boost Plus; 360 calories, 14 g fat), mean peak plasma posaconazole concentrations and AUC were both approximately threefold higher than following administration in the fasted state.1 15 71 Bioavailability of posaconazole is lower if the dose is administered with < 240 mL of the nutritional supplement;71 posaconazole bioavailability is about 20% lower if only 120 mL of the liquid nutritional supplement is used instead of 240 mL.71, Oral suspension: Following a single 400-mg dose given with an acidic beverage (i.e., ginger ale) in healthy adults in the fasted state, mean peak plasma posaconazole concentrations and AUC were increased by 92 and 70%, respectively, compared with administration alone in the fasted state.1, Delayed-release tablets: Following a single 300-mg dose given with a high-fat meal, peak plasma posaconazole concentrations and AUC were increased by 16 and 51%, respectively, compared with administration in the fasted state.1, Oral suspension in pediatric patients 13–17 years of age: When a dosage of 200 mg 3 times daily was used for prophylaxis of invasive fungal infections, mean steady-state plasma posaconazole concentrations were similar to those reported in adults.1, Oral suspension in pediatric patients 8–17 years of age: When a dosage of 400 mg twice daily or 200 mg 4 times daily was used for treatment of invasive fungal infections†, mean steady-state plasma posaconazole concentrations were similar to those reported in adults.1 48 51, Oral suspension in individuals with mild, moderate, or severe hepatic impairment: Mean AUC of posaconazole following a single 400-mg dose given after a high-fat meal was 43, 27, or 21% higher, respectively, and mean peak plasma concentration was 1% higher, 40% higher, or 34% lower, respectively, compared with individuals with normal hepatic function.1 41, Oral suspension in individuals with mild or moderate renal impairment (eGFR 20–80 mL/minute per 1.73 m2): Pharmacokinetics following a single dose was similar to that reported in individuals with normal renal function.1, Oral suspension in individuals with severe renal impairment (eGFR <20 mL/minute per 1.73 m2): Mean AUC of posaconazole following a single dose was similar to that reported in individuals with normal renal function; however, range of AUC estimates was highly variable compared with that in those with mild or moderate renal impairment.1, Delayed-release tablets in individuals with hepatic impairment: Specific studies not performed to date.1, Delayed-release tablets in individuals with renal impairment: Manufacturer states no clinically important effect on pharmacokinetics.1 Although specific studies not performed to date using the delayed-release tablets, posaconazole exposures in those with severe renal impairment are expected to be highly variable.1, Patients weighing >120 kg: Pharmacokinetic modeling suggests that posaconazole plasma concentrations may be lower than in other patients.1, Detected in skin72 and in pulmonary epithelial lining fluid and alveolar cell tissue following administration of posaconazole oral suspension.73, Distributed into milk in rats;1 not known whether distributed into milk in humans.1, Principally metabolized via uridine diphosphate (UDP)-glucuronosyltransferase glucuronidation (UGT; phase 2 enzymes).1 2 40 51 Posaconazole circulates in plasma principally as the parent drug; the majority of circulating metabolites are glucuronide conjugates formed via UDP glucuronidation.1, No major circulating metabolites formed via CYP isoenzymes.1, Oral suspension: 71% of a dose recovered in feces over 120 hours (66% as parent drug);1 2 4 5 13% of a dose recovered in urine over 120 hours (<0.2% as parent drug).1 2 5 6 Metabolites recovered in urine and feces represent approximately 17% of a dose.1, Oral suspension: 35 hours (range: 20–66 hours).1 15 39 61, Oral suspension in individuals with mild, moderate, or severe hepatic impairment: Mean apparent oral clearance following a single 400-mg dose was decreased 18, 36, or 28%, respectively, compared with individuals with normal hepatic function.1 Elimination half-life is 39, 27, or 43 hours in those with mild, moderate, or severe hepatic impairment, respectively.1, IV infusion in moderate or severe renal impairment (eGFR <50 mL/minute): IV vehicle contained in the preparation (SBECD) is expected to accumulate.1 (See Renal Impairment under Cautions.
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