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Noxafil

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Noxafil

Side Effects
Interactions

SIDE EFFECTS

Serious And Otherwise Important Adverse Reactions

The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of Noxafil cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, the type of adverse reactions reported for posaconazole injection and posaconazole delayed-release tablets were generally similar to that reported in trials of posaconazole oral suspension.

Clinical Trial Experience with Posaconazole Injection

Multiple doses of posaconazole injection administered via a peripheral venous catheter were associated with thrombophlebitis (60% incidence). Therefore, in subsequent studies, posaconazole injection was administered via central venous catheter.

The safety of posaconazole injection has been assessed in 268 patients in a clinical trial. Patients were enrolled in a non-comparative pharmacokinetic and safety trial of posaconazole injection when given as antifungal prophylaxis (Posaconazole Injection Study 1). Patients were immunocompromised with underlying conditions including hematological malignancy, neutropenia post-chemotherapy, GVHD, and post HSCT. This patient population was 55% male, had a mean age of 51 years (range 18-82 years, 19% of patients were ≥ 65 years of age), and were 95% white and 8% Hispanic. Ten patients received a single dose of 200 mg posaconazole injection, 21 patients received 200 mg daily dose for a median of 14 days, and 237 patients received 300 mg daily dose for a median of 9 days.

Table 4 presents treatment-emergent adverse reactions observed in patients treated with posaconazole injection 300 mg daily dose in the posaconazole injection study. Each patient received a loading dose, 300 mg twice on Day 1. Following posaconazole intravenous therapy, patients received posaconazole oral suspension to complete 28 days of total posaconazole therapy.

Table 4: Posaconazole Injection Study 1: Number (%) of Subjects Treated with Posaconazole Injection 300 mg Daily Dose Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10%

Body System
Preferred Term
Posaconazole Injection Treatment Phase
n=237 (%)*
Posaconazole Injection Treatment Phase or Subsequent Oral Suspension Treatment Phase
n=237(%)†
Subjects Reporting any Adverse Reaction 220 (93) 235 (99)
Blood and Lymphatic System Disorder
Anemia 16 (7) 23 (10)
Thrombocytopenia 17 (7) 25 (11)
Gastrointestinal Disorders
Abdominal Pain Upper 15 (6) 25 (11)
Abdominal Pain 30 (13) 41 (17)
Constipation 18 (8) 31 (13)
Diarrhea 75 (32) 93 (39)
Nausea 46 (19) 70 (30)
Vomiting 29 (12) 45 (19)
General Disorders and Administration Site Conditions
Fatigue 19 (8) 24 (10)
Chills 28 (12) 38 (16)
Edema Peripheral 28 (12) 35 (15)
Pyrexia 49 (21) 73 (31)
Metabolism and Nutrition Disorders
Decreased appetite 23 (10) 29 (12)
Hypokalemia 51 (22) 67 (28)
Hypomagnesemia 25 (11) 30 (13)
Nervous System Disorders
Headache 33 (14) 49 (21)
Respiratory, Thoracic and Mediastinal Disorders
Cough 21 (9) 31 (13)
Dyspnea 16 (7) 24 (10)
Epistaxis 34 (14) 40 (17)
Skin and Subcutaneous Tissue Disorders
Petechiae 20 (8) 24 (10)
Rash 35 (15) 56 (24)
Vascular Disorders
Hypertension 20 (8) 26 (11)
*Adverse reactions reported in patients with an onset during the posaconazole intravenous dosing phase of the study.
†Adverse reactions reported with an onset at any time during the study in patients who were treated for up to 28 days of posaconazole therapy.

The most frequently reported adverse reactions with an onset during the posaconazole intravenous phase of dosing with 300 mg once daily were diarrhea (32%), hypokalemia (22%), pyrexia (21%), and nausea (19%). These adverse reactions were consistent with those seen in studies with Noxafil oral suspension.

Clinical Trial Experience with Posaconazole Delayed-Release Tablets

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 (Delayed-Release Tablet Study 1). 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 19-78 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 5 presents treatment-emergent adverse reactions observed in patients treated with 300 mg daily dose at an incidence of ≥ 10% in posaconazole delayed-release tablet study.

Table 5: Posaconazole Delayed-Release Tablet Study 1: Number (%) of Subjects Treated with 300 mg Daily Dose Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10%

Body System
Preferred Term
Posaconazole delayed-release tablet (300 mg)
(n=210)
Subjects Reporting any Adverse Reaction 201 (99)
Blood and Lymphatic System Disorder
Anemia 22 (10)
Thrombocytopenia 29 (14)
Gastrointestinal Disorders
Abdominal Pain 23 (11)
Constipation 20 (10)
Diarrhea 61 (29)
Nausea 56 (27)
Vomiting 28 (13)
General 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)
Nervous System Disorders
Headache 30 (14)
Respiratory, 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%).

Clinical Trial Safety Experience with Posaconazole Oral Suspension

The safety of posaconazole oral suspension has been assessed in 1844 patients. This includes 605 patients in the active-controlled prophylaxis studies, 557 patients in the active-controlled OPC studies, 239 patients in refractory OPC studies, and 443 patients from other indications. This represents a heterogeneous population, including immunocompromised patients, e.g., patients with hematological malignancy, neutropenia post-chemotherapy, GVHD post HSCT, and HIV infection, as well as nonneutropenic patients. This patient population was 71% male, had a mean age of 42 years (range 8-84 years, 6% of patients were ≥ 65 years of age and 1% was < 18 years of age), and were 64% white, 16% Hispanic, and 36% non-white (including 14% black). Posaconazole therapy was given to 171 patients for ≥ 6 months, with 58 patients receiving posaconazole therapy for ≥ 12 months. Table 6 presents treatment-emergent adverse reactions observed at an incidence of > 10% in posaconazole prophylaxis studies. Table 7 presents treatment-emergent adverse reactions observed at an incidence of at least 10% in the OPC/rOPC studies.

Prophylaxis of Aspergillus and Candida: In the 2 randomized, comparative prophylaxis studies (Oral Suspension Studies 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 the prophylaxis clinical trials were fever, diarrhea, and nausea.

The most common adverse reactions leading to discontinuation of posaconazole in the prophylaxis studies were associated with GI disorders, specifically, nausea (2%), vomiting (2%), and hepatic enzymes increased (2%).

Table 6: Posaconazole Oral Suspension Study 1 and Study 2. Number (%) of Randomized Subjects Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10% in the Posaconazole Oral Suspension or Fluconazole Treatment Groups (Pooled Prophylaxis Safety Analysis)

Body System Preferred Term Posaconazole (n=605) Fluconazole (n=539) Itraconazole (n=58)
Subjects Reporting any Adverse Reaction 595 (98) 531 (99) 58 (100)
Body as a Whole - General Disorders
Fever 274 (45) 254 (47) 32 (55)
Headache 171 (28) 141 (26) 23 (40)
Rigors 122 (20) 87 (16) 17 (29)
Fatigue 101 (17) 98 (18) 5 (9)
Edema Legs 93 (15) 67 (12) 11 (19)
Anorexia 92 (15) 94 (17) 16 (28)
Dizziness 64 (11) 56 (10) 5 (9)
Edema 54 (9) 68 (13) 8 (14)
Weakness 51 (8) 52 (10) 2 (3)
Cardiovascular Disorders, General
Hypertension 106 (18) 88 (16) 3 (5)
Hypotension 83 (14) 79 (15) 10 (17)
Disorders of Blood and Lymphatic System
Anemia 149 (25) 124 (23) 16 (28)
Neutropenia 141 (23) 122 (23) 23 (40)
Disorders of the Reproductive System and Breast
Vaginal Hemorrhage* 24 (10) 20 (9) 3 (12)
Gastrointestinal System Disorders
Diarrhea 256 (42) 212 (39) 35 (60)
Nausea 232 (38) 198 (37) 30 (52)
Vomiting 174 (29) 173 (32) 24 (41)
Abdominal Pain 161 (27) 147 (27) 21 (36)
Constipation 126 (21) 94 (17) 10 (17)
Dyspepsia 61 (10) 50 (9) 6 (10)
Heart Rate and Rhythm Disorders
Tachycardia 72 (12) 75 (14) 3 (5)
Infection and Infestations
Pharyngitis 71 (12) 60 (11) 12 (21)
Liver and Biliary System Disorders
Bilirubinemia 59 (10) 51 (9) 11 (19)
Metabolic and Nutritional Disorders
Hypokalemia 181 (30) 142 (26) 30 (52)
Hypomagnesemia 110 (18) 84 (16) 11 (19)
Hyperglycemia 68 (11) 76 (14) 2 (3)
Hypocalcemia 56 (9) 55 (10) 5 (9)
Musculoskeletal System Disorders
Musculoskeletal Pain 95 (16) 82 (15) 9 (16)
Arthralgia 69 (11) 67 (12) 5 (9)
Back Pain 63 (10) 66 (12) 4 (7)
Platelet, Bleeding and Clotting Disorders
Thrombocytopenia 175 (29) 146 (27) 20 (34)
Petechiae 64 (11) 54 (10) 9 (16)
Psychiatric Disorders
Insomnia 103 (17) 92 (17) 11 (19)
Respiratory System Disorders
Coughing 146 (24) 130 (24) 14 (24)
Dyspnea 121 (20) 116 (22) 15 (26)
Epistaxis 82 (14) 73 (14) 12 (21)
Skin and Subcutaneous Tissue Disorders
Rash 113 (19) 96 (18) 25 (43)
Pruritus 69 (11) 62 (12) 11 (19)
* Percentages of sex-specific adverse reactions are based on the number of males/females.

HIV Infected Subjects with OPC: In 2 randomized comparative studies in OPC, the safety of posaconazole oral suspension at a dose of less than or equal to 400 mg QD in 557 HIV-infected patients was compared to the safety of fluconazole in 262 HIV-infected patients at a dose of 100 mg QD.

An additional 239 HIV-infected patients with refractory OPC received posaconazole oral suspension in 2 non-comparative trials for refractory OPC (rOPC). Of these subjects, 149 received the 800-mg/day dose and the remainder received the less than or equal to 400-mg QD dose.

In the OPC/rOPC studies, the most common adverse reactions were fever, diarrhea, nausea, headache, vomiting, and coughing.

The most common adverse reactions that led to treatment discontinuation of posaconazole in the Controlled OPC Pool included respiratory impairment (1%) and pneumonia (1%). In the refractory OPC pool, the most common adverse reactions that led to treatment discontinuation of posaconazole were AIDS (7%) and respiratory impairment (3%).

Table 7: Treatment-Emergent Adverse Reactions with Frequency of at Least 10% in OPC Studies with Posaconazole Oral Suspension (Treated Population)

Body System
Preferred Term
Number (%) of Subjects
Controlled OPC Pool Refractory OPC Pool
Posaconazole
n=557
Fluconazole
n=262
Posaconazole
n=239
Subjects Reporting any Adverse Reaction* 356 (64) 175 (67) 221 (92)
Body as a Whole - General Disorders
  Fever 34 (6) 22 (8) 82 (34)
  Headache 44 (8) 23 (9) 47 (20)
  Anorexia 10 (2) 4 (2) 46 (19)
  Fatigue 18 (3) 12 (5) 31 (13)
  Asthenia 9 (2) 5 (2) 31 (13)
  Rigors 2 ( < 1) 4 (2) 29 (12)
  Pain 4 (1) 2 (1) 27 (11)
Disorders of Blood and Lymphatic System
  Neutropenia 21 (4) 8 (3) 39 (16)
  Anemia 11 (2) 5 (2) 34 (14)
Gastrointestinal System Disorders
  Diarrhea 58 (10) 34 (13) 70 (29)
  Nausea 48 (9) 30 (11) 70 (29)
  Vomiting 37 (7) 18 (7) 67 (28)
  Abdominal Pain 27 (5) 17 (6) 43 (18)
Infection and Infestations
  Candidiasis, Oral 3 (1) 1 ( < 1) 28 (12)
  Herpes Simplex 16 (3) 8 (3) 26 (11)
  Pneumonia 17 (3) 6 (2) 25 (10)
Metabolic and Nutritional Disorders
  Weight Decrease 4 (1) 2 (1) 33 (14)
  Dehydration 4 (1) 7 (3) 27 (11)
Psychiatric Disorders
  Insomnia 8 (1) 3 (1) 39 (16)
Respiratory System Disorders
  Coughing 18 (3) 11 (4) 60 (25)
  Dyspnea 8 (1) 8 (3) 28 (12)
Skin and Subcutaneous Tissue Disorders
  Rash 15 (3) 10 (4) 36 (15)
  Sweating Increased 13 (2) 5 (2) 23 (10)
OPC=oropharyngeal candidiasis
* Number of subjects reporting treatment-emergent adverse reactions at least once during the study, without regard to relationship to treatment. Subjects may have reported more than 1 event.

Adverse reactions were reported more frequently in the pool of patients with refractory OPC. Among these highly immunocompromised patients with advanced HIV disease, serious adverse reactions (SARs) were reported in 55% (132/239). The most commonly reported SARs were fever (13%) and neutropenia (10%).

Less Common Adverse Reactions: Clinically significant adverse reactions reported during clinical trials in prophylaxis, OPC/rOPC or other trials with posaconazole which occurred in less than 5% of patients are listed below:

Clinical Laboratory Values: In healthy volunteers and patients, elevation of liver function test values did not appear to be associated with higher plasma concentrations of posaconazole.

For the prophylaxis studies, the number of patients with changes in liver function tests from Common Toxicity Criteria (CTC) Grade 0, 1, or 2 at baseline to Grade 3 or 4 during the study is presented in Table 8.

Table 8: Posaconazole Oral Suspension Study 1 and Study 2. Changes in Liver Function Test Results from CTC Grade 0, 1, or 2 at Baseline to Grade 3 or 4

Number (%) of Patients With Change* Oral Suspension Study 1
Laboratory Parameter Posaconazole
n=301
Fluconazole
n=299
  AST 11/266 (4) 13/266 (5)
  ALT 47/271 (17) 39/272 (14)
  Bilirubin 24/271 (9) 20/275 (7)
  Alkaline Phosphatase 9/271 (3) 8/271 (3)
Oral Suspension Study 2
Laboratory Parameter Posaconazole (n=304) Fluconazole/Itraconazole (n=298)
  AST 9/286 (3) 5/280 (2)
  ALT 18/289 (6) 13/284 (5)
  Bilirubin 20/290 (7) 25/285 (9)
  Alkaline Phosphatase 4/281 (1) 1/276 ( < 1)
*Change from Grade 0 to 2 at baseline to Grade 3 or 4 during the study. These data are presented in the form X/Y, where X represents the number of patients who met the criterion as indicated, and Y represents the number of patients who had a baseline observation and at least one post-baseline observation.
CTC = Common Toxicity Criteria; AST= Aspartate Aminotransferase; ALT= Alanine Aminotransferase.

The number of patients treated for OPC with clinically significant liver function test (LFT) abnormalities at any time during the studies is provided in Table 9 (LFT abnormalities were present in some of these patients prior to initiation of the study drug).

Table 9: Posaconazole Oral Suspension Studies: Clinically Significant Laboratory Test Abnormalities without Regard to Baseline Value

Laboratory Test Controlled Refractory
Posaconazole
n=557(%)
Fluconazole
n=262(%)
Posaconazole
n=239(%)
ALT > 3.0 x ULN 16/537 (3) 13/254 (5) 25/226 (11)
AST > 3.0 x ULN 33/537 (6) 26/254 (10) 39/223 (17)
Total Bilirubin > 1.5 x ULN 15/536 (3) 5/254 (2) 9/197 (5)
Alkaline Phosphatase > 3.0 x ULN 17/535 (3) 15/253 (6) 24/190 (13)
ALT= Alanine Aminotransferase; AST= Aspartate Aminotransferase.

Postmarketing Experience

No clinically significant postmarketing adverse reactions were identified that have not previously been reported during clinical trials experience.

Read the Noxafil (posaconazole oral suspension) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Posaconazole is primarily metabolized via UDP glucuronosyltransferase and is a substrate of pglycoprotein (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].

The following information was derived from data with posaconazole oral suspension or early tablet formulation. All drug interactions with posaconazole oral suspension, except for those that affect the absorption of posaconazole (via gastric pH and motility) are considered relevant to posaconazole injection as well.

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 and CLINICAL PHARMACOLOGY].

Tacrolimus: Posaconazole has been shown to significantly increase the Cmax 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 and CLINICAL PHARMACOLOGY].

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 and CLINICAL PHARMACOLOGY].

CYP3A4 Substrates

Concomitant administration of posaconazole with CYP3A4 substrates such as pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and cases of torsades de pointes. Therefore, posaconazole is contraindicated with these drugs [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

HMG-CoA Reductase Inhibitors (Statins) Primarily Metabolized Through CYP3A4

Concomitant administration of posaconazole with simvastatin increases the simvastatin plasma concentrations by approximately 10-fold. Therefore, posaconazole is contraindicated with HMG-CoA reductase inhibitors primarily metabolized through CYP3A4 [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY].

Ergot Alkaloids

Most of the ergot alkaloids are substrates of CYP3A4. Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism. Therefore, posaconazole is contraindicated with ergot alkaloids [see CONTRAINDICATIONS].

Benzodiazepines Metabolized by CYP3A4

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. Concomitant use of posaconazole and other benzodiazepines metabolized by CYP3A4 (e.g., alprazolam, triazolam) could result in increased plasma concentrations of these benzodiazepines. Patients must be monitored closely for adverse effects associated with high plasma concentrations of benzodiazepines metabolized by CYP3A4 and benzodiazepine receptor antagonists must be available to reverse these effects [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Anti-HIV Drugs

Efavirenz: Efavirenz induces UDP-glucuronidase and significantly decreases posaconazole plasma concentrations [see CLINICAL PHARMACOLOGY]. It is recommended to avoid concomitant use of efavirenz with posaconazole unless the benefit outweighs the risks.

Ritonavir and Atazanavir: Ritonavir and atazanavir are metabolized by CYP3A4 and posaconazole increases plasma concentrations of these drugs [see CLINICAL PHARMACOLOGY]. Frequent monitoring of adverse effects and toxicity of ritonavir and atazanavir should be performed during coadministration with posaconazole.

Fosamprenavir: Combining fosamprenavir with posaconazole may lead to decreased posaconazole plasma concentrations. If concomitant administration is required, close monitoring for breakthrough fungal infections is recommended [see CLINICAL PHARMACOLOGY].

Rifabutin

Rifabutin induces UDP-glucuronidase and decreases posaconazole plasma concentrations. Rifabutin is also metabolized by CYP3A4. Therefore, coadministration of rifabutin with posaconazole increases rifabutin plasma concentrations [see CLINICAL PHARMACOLOGY]. Concomitant use of posaconazole and rifabutin should be avoided unless the benefit to the patient outweighs the risk. However, if concomitant administration is required, close monitoring for breakthrough fungal infections as well as frequent monitoring of full blood counts and adverse reactions due to increased rifabutin plasma concentrations (e.g., uveitis, leukopenia) are recommended.

Phenytoin

Phenytoin induces UDP-glucuronidase and decreases posaconazole plasma concentrations. Phenytoin is also metabolized by CYP3A4. Therefore, coadministration of phenytoin with posaconazole increases phenytoin plasma concentrations [see CLINICAL PHARMACOLOGY]. Concomitant use of posaconazole and phenytoin should be avoided unless the benefit to the patient outweighs the risk. However, if concomitant administration is required, close monitoring for breakthrough fungal infections is recommended and frequent monitoring of phenytoin concentrations should be performed while coadministered with posaconazole and dose reduction of phenytoin should be considered.

Gastric Acid Suppressors/Neutralizers

Posaconazole Delayed-Release Tablet

No clinically relevant effects on the pharmacokinetics of posaconazole were observed when posaconazole delayed-release tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors [see CLINICAL PHARMACOLOGY]. No dosage adjustment of posaconazole delayed-release tablets is required when posaconazole delayed-release tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors.

Posaconazole Oral Suspension

Cimetidine (an H2-receptor antagonist) and esomeprazole (a proton pump inhibitor) when given with posaconazole oral suspension results in decreased posaconazole plasma concentrations [see CLINICAL PHARMACOLOGY]. It is recommended to avoid concomitant use of cimetidine and esomeprazole with posaconazole oral suspension unless the benefit outweighs the risks. However, if concomitant administration is required, close monitoring for breakthrough fungal infections is recommended.

No clinically relevant effects were observed when posaconazole oral suspension is concomitantly used with antacids and H2-receptor antagonists other than cimetidine. No dosage adjustment of posaconazole oral suspension is required when posaconazole oral suspension is concomitantly used with antacids and H2-receptor antagonists other than cimetidine.

Vinca Alkaloids

Most of the vinca alkaloids are substrates of CYP3A4. Posaconazole may increase the plasma concentrations of vinca alkaloids (e.g., vincristine and vinblastine) which may lead to neurotoxicity. Therefore, it is recommended that dose adjustment of the vinca alkaloid be considered.

Calcium Channel Blockers Metabolized By CYP3A4

Posaconazole may increase the plasma concentrations of calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, diltiazem, nifedipine, nicardipine, felodipine). Frequent monitoring for adverse reactions and toxicity related to calcium channel blockers is recommended during coadministration. Dose reduction of calcium channel blockers may be needed.

Digoxin

Increased plasma concentrations of digoxin have been reported in patients receiving digoxin and posaconazole. Therefore, monitoring of digoxin plasma concentrations is recommended during coadministration.

Gastrointestinal Motility Agents

Posaconazole Delayed-Release Tablet

Concomitant administration of metoclopramide with posaconazole delayed-release tablets did not affect the pharmacokinetics of posaconazole [see CLINICAL PHARMACOLOGY]. No dosage adjustment of posaconazole delayed-release tablets is required when given concomitantly with metoclopramide.

Posaconazole Oral Suspension

Metoclopramide, when given with posaconazole oral suspension, decreases posaconazole plasma concentrations [see CLINICAL PHARMACOLOGY]. If metoclopramide is concomitantly administered with posaconazole oral suspension, it is recommended to closely monitor for breakthrough fungal infections.

Loperamide does not affect posaconazole plasma concentrations after posaconazole oral suspension administration [see CLINICAL PHARMACOLOGY]. No dosage adjustment of posaconazole is required when loperamide and posaconazole are used concomitantly.

Glipizide

Although no dosage adjustment of glipizide is required, it is recommended to monitor glucose concentrations when posaconazole and glipizide are concomitantly used.

Read the Noxafil Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 4/1/2014
This monograph has been modified to include the generic and brand name in many instances.

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