Posaconazole is an azole antifungal indicated as follows:
Posaconazole is indicated for the prophylaxis of invasive Aspergillus and Candida infections in adults and pediatric patients 13 years of age and older 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. ( 1.2 )
Posaconazole oral suspension is indicated for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory (rOPC) to itraconazole and/or fluconazole in adults and pediatric patients aged 13 years and older. ( 1.3 )
1.2Prophylaxis of Invasive Aspergillus and Candida Infections
Posaconazole is indicated for the prophylaxis of invasive Aspergillus and Candida infections in adults and pediatric patients 13 years of age and older 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.
1.3 Treatment of Oropharyngeal Candidiasis Including Oropharyngeal Candidiasis Refractory to Itraconazole and/or Fluconazole Posaconazole oral suspension is indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole in adults and pediatric patients 13 years of age and older.
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 , 7.2 )
CYP3A4 Substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes (TdP) ( 4.3 , 5.2 , 7.2 )
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 , 7.2 )
4.1Hypersensitivity
Posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents.
4.2Use 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 ( 7.2 ) and Clinical Pharmacology ( 12.3 )] .
4.3QT 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 ( 7.2 ) and Clinical Pharmacology ( 12.3 )] .
4.5Use with Ergot Alkaloids
Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions ( 7.2 )] .
4.6Use 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 ( 7.2 )] .
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 , 7.2 )
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. ( 5.7 , 7.2 )
Vincristine Toxicity : Concomitant administration of azole antifungals, including posaconazole, with vincristine has been associated with neurotoxicity and other serious adverse reactions; reserve azole antifungals, including posaconazole, for patients receiving a vinca alkaloid, including vincristine, who have no alternative antifungal treatment options. ( 5.8 , 7.2 )
Breakthrough Fungal Infections : Monitor patients with severe diarrhea or vomiting when receiving posaconazole oral suspension. ( 5.10 )
Venetoclax Toxicity : Concomitant administration of posaconazole with venetoclax may increase venetoclax toxicities, including the risk of tumor lysis syndrome, neutropenia, and serious infections; monitor for toxicity and reduce venetoclax dose. ( 4.6 , 5.11 , 7.2 )
5.1Calcineurin-Inhibitor Toxicity
Concomitant administration of posaconazole with cyclosporine or tacrolimus increases the whole blood trough concentrations of these calcineurin-inhibitors [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )]. Nephrotoxicity and leukoencephalopathy (including deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine or tacrolimus concentrations. Frequent monitoring of tacrolimus or cyclosporine whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus or cyclosporine dose adjusted accordingly.
5.2Arrhythmias and QT Prolongation
Some azoles, including posaconazole, have been associated with prolongation of the QT interval on the electrocardiogram. In addition, cases of torsades de pointes have been reported in patients taking posaconazole. Results from a multiple time-matched ECG analysis in healthy volunteers did not show any increase in the mean of the QTc interval. Multiple, time-matched ECGs collected over a 12-hour period were recorded at baseline and steady-state from 173 healthy male and female volunteers (18 to 85 years of age) administered posaconazole oral suspension 400 mg twice daily with a high-fat meal.
In this pooled analysis, the mean QTc (Fridericia) interval change from baseline was –5 msec following administration of the recommended clinical dose. A decrease in the QTc(F) interval (–3 msec) was also observed in a small number of subjects (n=16) administered placebo. The placebo-adjusted mean maximum QTc(F) interval change from baseline was <0 msec (–8 msec). No healthy subject administered posaconazole had a QTc(F) interval ≥500 msec or an increase ≥60 msec in their QTc(F) interval from baseline.
Posaconazole should be administered with caution to patients with potentially proarrhythmic conditions. Do not administer with drugs that are known to prolong the QTc interval and are metabolized through CYP3A4 [see Contraindications ( 4.3 ) and Drug Interactions ( 7.2 )] .
5.3Electrolyte Disturbances
Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during posaconazole therapy.
5.4Pseudoaldosteronism
Pseudoaldosteronism, manifested by the onset of hypertension or worsening of hypertension, and abnormal laboratory findings (hypokalemia, low serum renin and aldosterone, and elevated 11-deoxycortisol), has been reported with posaconazole use in the postmarket setting. Monitor blood pressure and potassium levels and manage as necessary. Management of pseudoaldosteronism may include discontinuation of posaconazole, substitution with an appropriate antifungal drug that is not associated with pseudoaldosteronism, or use of aldosterone receptor antagonists.
5.5Hepatic Toxicity
Hepatic reactions (e.g., mild to moderate elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and/or clinical hepatitis) have been reported in clinical trials. The elevations in liver tests were generally reversible on discontinuation of therapy, and in some instances these tests normalized without drug interruption. Cases of more severe hepatic reactions including cholestasis or hepatic failure including deaths have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with posaconazole.
These severe hepatic reactions were seen primarily in subjects receiving the posaconazole oral suspension 800 mg daily (400 mg twice daily or 200 mg four times a day) in clinical trials. Liver tests should be evaluated at the start of and during the course of posaconazole therapy. Patients who develop abnormal liver tests during posaconazole therapy should be monitored for the development of more severe hepatic injury.
Patient management should include laboratory evaluation of hepatic function (particularly liver tests and bilirubin). Discontinuation of posaconazole must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to posaconazole.
5.6 Renal Impairment Due to the variability in exposure with posaconazole oral suspension, patients with severe renal impairment should be monitored closely for breakthrough fungal infections [see Dosage and Administration ( 2.11 ) and Use in Specific Populations ( 8.6 )].
5.7Midazolam Toxicity
Concomitant administration of posaconazole with midazolam increases the midazolam plasma concentrations by approximately 5-fold. Increased plasma midazolam concentrations could potentiate and prolong hypnotic and sedative effects. Patients must be monitored closely for adverse effects associated with high plasma concentrations of midazolam and benzodiazepine receptor antagonists must be available to reverse these effects [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )] .
5.8Vincristine Toxicity
Concomitant administration of azole antifungals, including posaconazole, with vincristine has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus. Reserve azole antifungals, including posaconazole, for patients receiving a vinca alkaloid, including vincristine, who have no alternative antifungal treatment options [see Drug Interactions ( 7.2 )] .
5.10Breakthrough Fungal Infections
Patients who have severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections when receiving posaconazole.
5.11Venetoclax Toxicity
Concomitant administration of posaconazole, a strong CYP3A4 inhibitor, with venetoclax may increase venetoclax toxicities, including the risk of tumor lysis syndrome (TLS), neutropenia, and serious infections. In patients with CLL/S
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Interactions
Table 15 and Table 17 include drugs with clinically important drug interactions when administered concomitantly with posaconazole and posaconazole PowderMix and instructions for preventing or managing them. Table 16 includes important drug interactions specific to the absorption of posaconazole administered as either posaconazole oral suspension or posaconazole PowderMix. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse reactions or loss of efficacy [see Clinical Pharmacology ( 12.3 )] .
The following information was derived from data with posaconazole oral suspension or another posaconazole tablet formulation unless otherwise noted. All clinically important drug interactions with posaconazole oral suspension, except for those that affect the absorption of posaconazole (via gastric pH and motility), are considered relevant to clinically important drug interactions with posaconazole injection, posaconazole delayed-release tablets, and posaconazole PowderMix for delayed-release oral suspension [Clinical Pharmacology ( 12.3 )] .
Consult the labeling of concomitantly used drugs to obtain further information about interactions with posaconazole. Interaction Drug Interaction Rifabutin, phenytoin, efavirenz, cimetidine, esomeprazole Avoid coadministration unless the benefit outweighs the risks ( 7.1 , 7.2 ) Other drugs metabolized by CYP3A4 Consider dosage adjustment and monitor for adverse effects and toxicity ( 7.2 ) Digoxin Monitor digoxin plasma concentrations ( 7.2 ) Fosamprenavir, metoclopramide Monitor for breakthrough fungal infections ( 7.3 , 12.3 )
7.1Effects of Other Drugs on Posaconazole
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. Concomitant use of posaconazole with drugs that can decrease the plasma posaconazole concentrations should generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections.
Table 15: Drug Interactions Affecting Posaconazole When Administered Concomitantly with Other Drugs UDP-Glucuronidase Inducers Mechanism and Clinical Effect(s) Posaconazole is a UDP-glucuronosyltransferase substrate. Concomitant use of posaconazole with UDP-glucuronidase inducers may decrease posaconazole exposure [see Clinical Pharmacology ( 12.3 )], which may reduce the effectiveness of posaconazole. Prevention or Management Efavirenz Avoid concomitant use of posaconazole with efavirenz, unless the benefit outweighs the risks.
Rifabutin Avoid concomitant use of posaconazole with rifabutin unless the benefit to the patient outweighs the risk. If concomitant use is needed, monitor closely for breakthrough fungal infections. See Table 17 for rifabutin monitoring considerations when posaconazole affects rifabutin via CYP3A4 inhibition. Phenytoin Avoid concomitant use of posaconazole with phenytoin unless the benefit to the patient outweighs the risk.
If concomitant use is needed, monitor for breakthrough fungal infections. See Table 17 for phenytoin monitoring considerations when posaconazole affects phenytoin via CYP3A4 inhibition. Fosamprenavir Mechanism and Clinical Effect(s) Concomitant use of posaconazole with fosamprenavir may lead to decreased posaconazole plasma concentrations [see Clinical Pharmacology ( 12.3 )], which may reduce effectiveness of posaconazole.
Prevention or Management If concomitant use of posaconazole with fosamprenavir is needed, monitor closely for breakthrough fungal infections. Table 16: Drug Interactions Affecting Posaconazole Oral Suspension Absorption When Administered Concomitantly with Other Drugs Posaconazole Oral Suspension Cimetidine and Esomeprazole Mechanism and Clinical Effect(s) Concomitant use of posaconazole oral suspension with cimetidine or esomeprazole resulted in decreased posaconazole plasma concentrations [see Clinical Pharmacology ( 12.3 )], which may reduce effectiveness of posaconazole.
Prevention or Management Avoid concomitant use of posaconazole oral suspension with cimetidine or esomeprazole unless the benefit outweighs the risks. If concomitant use is needed, monitor closely for breakthrough fungal infections. Metoclopramide Mechanism and Clinical Effect(s) Concomitant use of posaconazole oral suspension with metoclopramide decreased posaconazole plasma concentrations [see Clinical Pharmacology ( 12.3 )], which may reduce effectiveness of posaconazole oral suspension.
Prevention or Management If posaconazole oral suspension is concomitantly administered with metoclopramide, closely monitor for breakthrough fungal infections.
7.2Effects of Posaconazole on Other Drugs
Posaconazole is a strong CYP3A4 inhibitor. Therefore, concomitant use of posaconazole may increase plasma concentrations of drugs that are CYP3A4 substrates [see Clinical Pharmacology (12.3)] . Table 17: Drug Interactions Affecting Drugs Administered Concomitantly with Posaconazole Digoxin Clinical Effect(s) Increased digoxin plasma concentrations have been reported in patients who received concomitant posaconazole and digoxin.
Prevention or Management Monitor digoxin plasma concentrations during concomitant use of posaconazole. Glipizide Clinical Effect(s) No dosage modification of glipizide is needed when used concomitantly with posaconazole. However, glucose concentrations decrease in some patients concomitantly administered posaconazole and glipizide. Prevention or Management Increase monitoring of glucose concentrations when used concomitantly.
CYP3A Substrates Immunosuppressants that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Posaconazole is a strong CYP3A4 inhibitor. Therefore, plasma concentrations of CYP3A4 substrates may be increased by posaconazole use [see Clinical Pharmacology (12.3)]. Prevention or Management Sirolimus Posaconazole is contraindicated with sirolimus [see Clinical Pharmacology ( 12.3 )] . Tacrolimus
At initiation of posaconazole treatment, reduce the tacrolimus dosage to approximately one-third of the original tacrolimus dosage.
Frequent monitoring of tacrolimus whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus dosage should be modified accordingly [see Warnings and Precautions (5.1) and Clinical Pharmacology ( 12.3 )] . Cyclosporine
At initiation of posaconazole treatment reduce the cyclosporine dosage to approximately three-fourths of the original dosage.
Frequent monitoring of cyclosporine whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the cyclosporine dosage should be modified accordingly [see Warnings and Precautions (5.1) and Clinical Pharmacology ( 12.3 )] . CYP3A4 Substrates that Prolong QTc Interval Mechanism and Clinical Effect(s) Concomitant use of posaconazole with CYP3A4 substrates such as pimozide and quinidine may result in increased plasma concentrations of the CYP3A4 substrates leading to QTc interval prolongation and torsades de pointes [see Warnings and Precautions ( 5.2 )]. Prevention or Management Pimozide Concomitant use with posaconazole is contraindicated. Quinidine HMG-CoA Reductase Inhibitors (Statins) that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Concomitant use of posaconazole with simvastatin increased simvastatin plasma concentrations which can lead to rhabdomyolysis [see Clinical Pharmacology ( 12.3 )]. Prevention or Management Atorvastatin, Lovastatin, Simvastatin Concomitant use with posaconazole is contraindicated. Benzodiazepines that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Concomitant use of posaconazole with midazolam increased midazolam plasma concentra
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Pregnancy and breastfeeding
8.1Pregnancy 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 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, doses of ≥ 3 times the clinical exposure caused an increase in resorptions (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 populations 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.
Adverse reactions
The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling:
Arrhythmias and QT Prolongation [see Warnings and Precautions ( 5.2 )]
Electrolyte Disturbances [see Warnings and Precautions ( 5.3 )]
Pseudoaldosteronism [see Warnings and Precautions ( 5.4 )]
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 Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 Trials Safety Experience with Posaconazole Oral Suspension: The safety of posaconazole oral suspension has been assessed in 1,844 patients, including:
605 patients in the active-controlled studies for the prophylaxis of invasive Aspergillus and Candida infections
557 patients in the active-controlled OPC studies (not refractory to itraconazole or fluconazole)
239 patients in refractory OPC studies (refractory to itraconazole or fluconazole) (rOPC), and
443 patients in other patient populations These studies included immunocompromised patients (e.g., patients with hematological malignancy, neutropenia post-chemotherapy, GVHD post HSCT, and HIV infection), as well as non-neutropenic patients. This patient population was 71% male, had a mean age of 42 years (range 8 to 84 years, 6% of patients were ≥65 years of age and 1% was <18 years of age), and were 64% White, 14% Black, 16% Hispanic. Posaconazole oral suspension therapy was given to 171 patients for ≥6 months, including 58 patients who received posaconazole oral suspension therapy for ≥12 months. Table 10 presents adverse reactions observed at an incidence of >10% in the studies for prophylaxis of invasive Aspergillus and Candida infections. Table 11 presents adverse reactions observed at an incidence of at least 10% in the OPC/rOPC studies. Prophylaxis of Invasive Aspergillus and Candida Infections (posaconazole oral suspension) : In the two randomized, comparative studies for prophylaxis Aspergillus and Candida infections in those at high risk of developing these infections due to being severely immunocompromised (Posaconazole Oral Suspension Study 1 and 2), the safety of posaconazole oral suspension 200 mg three times a day was compared to fluconazole 400 mg once daily or itraconazole 200 mg twice a day in severely immunocompromised patients. The most frequently reported adverse reactions (>30%) in these trials were fever, diarrhea, and nausea. The most common adverse reactions leading to discontinuation of posaconazole oral suspension were GI adverse reactions, specifically, nausea (2%), vomiting (2%), and increased hepatic enzymes (2%). Table 10: Adverse Reactions in at least 10% of Patients Receiving Posaconazole Oral Suspension for the Prophylaxis of Invasive Aspergillus and Candida Infections Adverse Reactions Posaconazole Oral Suspension n=605 (%) Fluconazole n=539 (%) Itraconazole n=58 (%) Percentage of Patients Reporting any Adverse Reaction 98 99 100 Fever 45 47 55 Diarrhea 42 39 60 Nausea 38 37 52 Hypokalemia 30 26 52 Thrombocytopenia 29 27 34 Vomiting 29 32 41 Headache 28 26 40 Abdominal Pain 27 27 36 Anemia 25 23 28 Coughing 24 24 24 Neutropenia 23 23 40 Constipation 21 17 17 Dyspnea 20 22 26 Rigors 20 16 29 Rash 19 18 43 Hypertension 18 16 5 Hypomagnesemia 18 16 19 Fatigue 17 18 9 Insomnia 17 17 19 Musculoskeletal Pain 16 15 16 Anorexia 15 17 28 Edema Legs 15 12 19 Epistaxis 14 14 21 Hypotension 14 15 17 Pharyngitis 12 11 21 Tachycardia 12 14 5 Arthralgia 11 12 9 Dizziness 11 10 9 Hyperglycemia 11 14 3 Petechiae 11 10 16 Pruritus 11 12 19 Back Pain 10 12 7 Bilirubinemia 10 9 19 Dyspepsia 10 9 10 Vaginal Hemorrhage Percentage of sex-specific adverse reactions are based on the number of males/females. 10 9 12 Treatment of Nonrefractory OPC and Refractory OPC (posaconazole oral suspension) In two randomized comparative studies for the treatment of nonrefractory OPC, the safety of posaconazole oral suspension (less than or equal to 400 mg once daily) in 557 HIV-infected patients was compared to the safety of fluconazole (100 mg once daily) in 262 HIV-infected patients. An additional 239 HIV-infected patients with refractory OPC (rOPC) received posaconazole oral suspension in two non-comparative trials for rOPC. Of these patients, 149 received the 800 mg/day dosage and the remainder received the less than or equal to 400 mg once daily dosage. In the nonrefractory OPC and rOPC studies, the most common adverse reactions in patients treated with posaconazole oral suspension were fever, diarrhea, nausea, headache, vomiting, and coughing. Adverse reactions were reported more frequently in the studies of patients with refractory OPC. Among these highly immunocompromised patients with advanced HIV disease, serious adverse reactions were reported in 55% (132/239) of posaconazole oral suspension-treated patients. The most commonly reported serious adverse reactions were fever (13%) and neutropenia (10%). Table 11: Adverse Reactions in at least 10% of Patients Receiving Posaconazole Oral Suspension for the Treatment of Nonrefractory and Refractory OPC Adverse Reactions Controlled OPC Pool Refractory OPC Pool Posaconazole Oral Suspension Fluconazole Posaconazole Oral Suspension n=557 (%) n=262 (%) n=239 (%) Percentage of Patients that Reported any Adverse Reaction Based on patients reporting adverse reactions at least once during the study, without regard to relationship to treatment. Patients may have reported more than 1 adverse reaction. 64 67 92 Diarrhea 10 13 29 Nausea 9 11 29 Headache 8 9 20 Vomiting 7 7 28 Fever 6 8 34 Abdominal Pain 5 6 18 Neutropenia 4 3 16 Coughing 3 4 25 Fatigue 3 5 13 Herpes Simplex 3 3 11 Pneumonia 3 2 10 Rash 3 4 15 Anemia 2 2 14 Anorexia 2 2 19 Asthenia 2 2 13 Sweating Increased 2 2 10 Candidiasis, Oral 1 <1 12 Dehydration 1 3 11 Dyspnea 1 3 12 Insomnia 1 1 16 Pain 1 1 11 Weight Decrease 1 <1 14 Rigors <1 2 12 OPC=oropharyngeal candidiasis Additional Adverse Reactions Reported in Less Than 5% of Posaconazole-Treated Patients in Clinical Trials Other clinically significant adverse reactions reported in less than 5% of patients in clinical trials of posaconazole are listed below:
Blood and Lymphatic System Disorders: hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, neutropenia aggravated
Endocrine Disorders: adrenal insufficiency
Nervous System Disorders: paresthesia
Immune System Disorders: allergic reaction [see Contraindications ( 4.1 )]
Cardiac Disorders: torsades de pointes [see Warnings and Precautions ( 5.2 )]
Vascular Disorders: pulmonary embolism
Gastrointestinal Disorders: pancreatitis
Liver and Biliary System Disorders: hepatic enzymes increased, hepatic function abnormal, hepatitis, hepatomegaly, jaundice
Renal & Urinary System Disorders: renal failure acute Liver Test Abnormalities in the Clinical Trials of Posaconazole Oral Suspension Liver Test Abnormalities in the Clinical Trials with Posaconazole Oral Suspension for Prophylaxis of Invasive Aspergillus and Candida Infections In the prophylaxis of invasive Aspergillus and Candida infections studies, the number and percentage of patients with changes in liver tests from Common Toxicity Criteria (CTC) Grade 0, 1, or 2 at baseline to Grade 3 or 4 at the end of the studies is presented in Table 12. Table 12: Changes in Liver Test Results from CTC Grade 0, 1, or 2 at Baseline to Grade 3 or 4 in Prophylaxis of Invasive Aspergillus and Candida Infections Studies (Posac
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Composition
Active ingredients
POSACONAZOLE 40MG/ML
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
