Posaconazole (Noxafil) is an antifungal drug that is available as an oral formulation for the treatment of invasive fungal infections including mucormycosis.
Indications of Posaconazole (Noxafil):
- Candidiasis, oropharyngeal:
- Suspension (≥13 years of age):
- It is effective in treating oropharyngeal candidiasis (including patients refractory to itraconazole and/or fluconazole).
- Suspension (≥13 years of age):
- Invasive fungal infections, prophylaxis:
- Suspension and delayed-release tablets (≥13 years of age) and injection (≥18 years of age):
- It is given as prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk such as severe immunocompromised states (eg, hematopoietic stem cell transplant recipients with graft-versus-host disease or those with prolonged neutropenia secondary to chemotherapy for hematologic malignancies).
- Suspension and delayed-release tablets (≥13 years of age) and injection (≥18 years of age):
- Off Label Use of Posaconazole in Adults:
- Aspergillosis, invasive treatment (refractory to or intolerant of conventional therapy);
- Candidiasis, esophageal (refractory to conventional therapy);
- Coccidioidomycosis, treatment (refractory to conventional therapy);
- Cryptococcal infections (pulmonary, non-immunosuppressed);
- Mucormycosis
Posaconazole (Noxafil) dose in adults:
Note:
- Interchanging of the delayed-release tablet and the oral suspension is not recommended due to dosing differences for each formulation.
- The delayed-release tablet is preferred due to easy administration, better tolerance, and better absorption.
- The bioavailability of a once-daily 300 mg dose given as the delayed-release tablet appears to be similar or greater than the bioavailability of 200 mg given 3 to 4 times daily, based upon available pharmacokinetic studies.
- The IV formulation is given at the same dose as the delayed-release tablet.
Posaconazole (Noxafil) treatment dose of invasive Aspergillosis:
- Prophylaxis (immunocompromised host):
- Suspension:
- 200 mg per oral 3 times daily.
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Posaconazole is started at the time of chemotherapy initiation (or if receiving anthracyclines, 24 hours after the last anthracycline dose) and was continued until recovery from neutropenia, until complete remission, or for up to 12 weeks, whichever occurred first in case of acute myelogenous leukemia or myelodysplastic syndrome.
- Posaconazole is given for 112 days in patients with graft-versus-host disease receiving immunosuppressive therapy, although the optimal duration in GVHD has not been fully defined. It is recommended to continue throughout the duration of immunosuppression (ie, corticosteroid equivalent of >1 mg/kg/day of prednisone for >2 weeks and/or the use of other anti-GVHD therapies).
- Tablet (delayed-release):
- Initial: 300 mg per oral twice daily on day 1 followed by 300 mg once daily on day 2 and thereafter. Duration depends on recovery from neutropenia or immunosuppression.
- Missed doses:
- It should be taken as soon as remembered. If it is <12 hours until the next dose, the missed dose should be skipped and the regular schedule should be followed.
- The dose should not be doubled.
- Loading dose:
- 300 mg IV twice a day on day 1 followed by 300 mg once daily on day 2 and thereafter.
- Duration is based on recovery from neutropenia or immunosuppression.
- Suspension:
- Posaconazole (Noxafil) dose in the treatment of fungal infections refractory to or intolerant of conventional therapy (off-label):
-
- Suspension:
- 200 mg per oral 3 times daily or
- 200 mg per oral q.i.d daily, then may switch to 400 mg b.i.d daily for outpatients).
- Tablet (delayed-release):
- Initial: 300 mg per oral twice daily on day 1;
- Maintenance: 300 mg once daily.
- Loading dose:
- 300 mg IV twice daily on day 1;
- Maintenance: 300 mg once daily.
- Suspension:
-
- Duration of therapy:
- Minimum of 6 to 12 weeks, although the duration is highly dependent on the degree/duration of immunosuppression, disease site, and evidence of disease improvement.
Posaconazole (Noxafil) dose in the treatment of Candidiasis:
- Prophylaxis (disseminated candidiasis, immunocompromised host):
- Suspension:
- 200 mg per oral 3 times daily;
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Tablet (delayed-release):
- Initial: 300 mg per oral twice daily on day 1;
- Maintenance: 300 mg once daily on day 2 and thereafter;
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses:
- It should be taken as soon as remembered. If it is <12 hours until the next dose, the missed dose should be skipped and the regular schedule should be followed. Doses should not be doubled.
- Initial:
- 300 mg IV twice daily on day 1;
- Maintenance:
- 300 mg once daily on day 2 and thereafter;
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Suspension:
- Treatment:
-
- Oropharyngeal infection:
- Suspension:
- Initial: 100 mg per oral twice daily on day 1;
- Maintenance: 100 mg once daily on day 2 and thereafter for 13 days.
- Suspension:
- Oropharyngeal infection (refractory to fluconazole):
- Suspension:
- 400 mg per oral twice daily (manufacturer's labeling) for 3 days, then 400 mg once daily for up to 28 days.
- Suspension:
- HIV-infected patients (alternative to fluconazole or azole refractory):
- Suspension:
- 400 mg per oral twice daily on day 1, then 400 mg once daily for 7 to 14 days for initial episodes (continue for 28 days in azole refractory patients).
- Suspension:
- Oropharyngeal infection:
-
Posaconazole (Noxafil) dose in the treatment of Esophageal infections (off-label):
- Fluconazole-refractory (alternate therapy):
- Tablet (delayed-release): 300 mg once daily.
- Suspension: 400 mg twice daily.
- HIV-infected patients (azole refractory):
- Suspension: 400 mg twice daily for 28 days.
- Note: If the patient has frequent or severe recurrences, may continue for suppressive therapy; consider discontinuing when CD4 >200/mm.
Posaconazole (Noxafil) dose in the treatment of Coccidioidomycosis (refractory to conventional therapy) (off-label):
- Nonmeningeal infection:
- Tablet (delayed-release):
- Initial: 300 mg per oral twice daily on day 1;
- Maintenance: 300 mg once daily on day 2 and thereafter.
- Suspension:
- 400 mg twice daily.
- Tablet (delayed-release):
- Duration of therapy:
- Varies by site and severity of infection, as well as host immunocompetence.
Posaconazole (Noxafil) dose in the treatment of Meningeal infection:
- Tablet (delayed-release):
- Initial: 300 mg per oral twice daily on day 1;
- Maintenance: 300 mg once daily on day 2 and thereafter.
- A higher maintenance dose of 200 to 300 mg twice daily, with routine therapeutic drug monitoring, is recommended by some experts.
- Suspension:
- 200 mg per oral 4 times daily or 400 mg twice daily.
- Duration of therapy:
- Treatment should be lifelong as there is a high relapse rate when the dose is decreased or treatment is discontinued.
Posaconazole (Noxafil) dose in the treatment of Cryptococcal infections (off-label):
- Pulmonary, non-immunosuppressed (alternative agent):
- Oral: Suspension: 400 mg twice daily.
- Salvage treatment of relapsed infection:
- Oral: Suspension:
- 400 mg twice daily (or 200 mg 4 times daily) for 10 to 12 weeks.
- Note: Salvage treatment should only be started after an appropriate course of an induction regimen.
- Oral: Suspension:
Posaconazole (Noxafil) dose in the treatment of Mucormycosis, salvage and step-down therapy (off-label):
- Oral:
- Suspension: 800 mg/day in 2 or 4 divided doses..
- Tablet (delayed-release): Initial: 300 mg twice daily on day 1; Maintenance: 300 mg once daily on day 2 and thereafter.
- IV:
- Initial: 300 mg every 12 hours on day 1;
- Maintenance: 300 mg every 24 hours thereafter (Cox 2019).
- Duration of therapy:
- Varies based on clinical and radiologic response and host immunocompetence.
Posaconazole (Noxafil) dose in children:
Note:
- The correct dosage form should be verified.
- Interchanging the delayed-release tablet and the oral suspension is not recommended.
Posaconazole (Noxafil) dose in HSCT recipients for antifungal prophylaxis: Limited data available:
- Infants ≥8 months and Children <12 years:
- Oral suspension:
- 4 mg/kg/dose 3 times daily;
- begin 2-4 days before discharge and continue until either day 100 post-HSCT or until CD T cells reach 200/mm and CD cells reach 100/mm³ whichever is longer.
- Dosing based on experience in 60 pediatric patients (median age: 6 years; age range: 0.7-11.5 years);
- pharmacokinetic analysis showed 12 mg/kg/day (4 mg/kg 3 times daily) produced morning serum trough concentration similar to effective adult values.
- The other evaluated regimen of 10 mg/kg/day (5 mg/kg twice daily) produced morning trough levels that were approximately 3 times lower than the thrice-daily regimen and were subsequently removed from the protocol.
- Overall, no patients developed invasive mycosis (probable or proven)
- No severe adverse effects were seen with the median duration of therapy of 127 days.
- Oral suspension:
- Adolescents ≥13 years:
- Oral suspension:
- 200 mg 3 times daily beginning with GVHD diagnosis, continue until GVHD resolves.
- Oral suspension:
Posaconazole (Noxafil) Dose for antifungal prophylaxis in acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS):
- Adolescents ≥13 years:
- Oral suspension:
- 200 mg 3 times daily during chemotherapy-associated neutropenia.
- Note: Consider in centers with high incidence of mold infections or if fluconazole not available.
- Oral suspension:
Posaconazole (Noxafil) Dose in the prophylaxis of invasive Aspergillosis:
- Adolescents ≥13 years:
- Oral delayed-release tablets (preferred):
- Initial: 300 mg twice daily for 1 day;
- maintenance dose: 300 mg once daily starting on Day 2;
- duration is based on recovery from neutropenia or immunosuppression.
- Missed doses:
- It should be taken as soon as remembered.
- If it is <12 hours until the next dose, the missed dose should be skipped and the regular schedule should be followed.
- Doses should not be doubled.
- Oral suspension:
- 200 mg 3 times daily; duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses:
- It should be taken as soon as remembered. If it is <12 hours until the next dose, the missed dose should be skipped and the regular schedule should be followed.
- Doses should not be doubled.
- Oral delayed-release tablets (preferred):
- IV:
- Adolescents ≥18 years:
- Loading dose: 300 mg twice a day on day 1;
- maintenance dose: 300 mg once daily on day 2 and thereafter.
- Duration is based on recovery from neutropenia or immunosuppression.
- Adolescents ≥18 years:
Posaconazole (Noxafil) Treatment dose of Candidiasis:
- Esophageal infection; azole -refractory (HIV-exposed/-positive):
- Treatment:
- Adolescent:
- Oral suspension: 400 mg per oral twice daily for 28 days.
- Note:
- If the patient has frequent or severe recurrences may continue for suppressive therapy;
- consider discontinuing when CD >200/mm³.
- Adolescent:
- Treatment:
- Invasive infections:
- Prophylaxis:
- Adolescents ≥13 years:
- Oral delayed-release tablets (preferred):
- Initial: 300 mg twice daily for 1 day;
- maintenance dose: 300 mg once daily. Duration is based on recovery from neutropenia or immunosuppression.
- Missed doses:
- It should be taken as soon as remembered.
- If it is <12 hours until the next dose, the missed dose should be skipped and the regular schedule should be followed.
- Doses should not be doubled.
- Oral suspension:
- 200 mg 3 times daily; duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses:
- It should be taken as soon as remembered.
- If it is <12 hours until the next dose, the missed dose should be skipped and the regular schedule should be followed.
- Doses should not be doubled.
- Oral delayed-release tablets (preferred):
- Adolescents ≥13 years:
- Treatment (refractory infection):
- Children ≥8 years and Adolescents:
- Oral suspension:
- 800 mg/day administered as either 200 mg 4 times daily or 400 mg twice daily;
- this regimen produced similar plasma concentrations in both children (n=12; age range: 8-17 years; weight: 24-76 kg) and adults.
- Oral suspension:
- Children ≥8 years and Adolescents:
- Prophylaxis:
Posaconazole (Noxafil) Treatment dose of Oropharyngeal infection:
- Non-HIV-exposed/-positive:
- Adolescents ≥13 years:
- Treatment:
- Oral suspension:
- Initial: 100 mg twice daily on day 1;
- maintenance: 100 mg once daily for 13 days.
- Oral suspension:
- Treatment (refractory infection):
- Oral suspension: 400 mg twice daily;
- The duration of therapy is based on the underlying disease and clinical response.
- Treatment:
- Adolescents ≥13 years:
- HIV-exposed/-positive:
- Treatment:
- Adolescents:
- Oral suspension:
- Initial: 400 mg twice daily on day 1;
- maintenance: 400 mg once daily for 28 days.
- Oral suspension:
- Adolescents:
- Treatment:
Posaconazole (Noxafil) Pregnancy Risk Category: B3
- Animal reproduction studies have shown that adverse events can be observed.
Posaconazole use during breastfeeding:
- It is unknown if breast milk secretes Posaconazole.
- The risk of infant exposure and the benefits of breastfeeding to the baby during therapy will all play a role in deciding whether to breastfeed.
Posaconazole (Noxafil) Dose adjustment in kidney disease:
- Delayed-release tablets and oral suspension:
- eGFR 20 to 80 mL/minute/1.73 m²:
- No dosage adjustment necessary.
- eGFR <20 mL/minute/1.73 m²:
- No dosage adjustment necessary; however, monitor for breakthrough fungal infections due to variability in posaconazole exposure.
- eGFR 20 to 80 mL/minute/1.73 m²:
- IV infusion:
- eGFR ≥50 mL/minute/1.73 m²:
- No dosage adjustment is necessary.
- eGFR <50 mL/minute/1.73 m²:
- Avoid use unless risk/benefit has been assessed; the intravenous vehicle (cyclodextrin) may accumulate. Monitor serum creatinine levels; if increases occur, consider oral therapy.
- Continuous venovenous hemofiltration (CVVH):
- In a critically ill patient undergoing CVVH, IV posaconazole administered at standard dosing demonstrated no evidence of cyclodextrin accumulation; however, no specific dosing recommendations can be made.
- eGFR ≥50 mL/minute/1.73 m²:
Posaconazole (Noxafil) Dose adjustment in liver disease:
- Preexisting mild-to-severe impairment (Child-Pugh class A, B, or C):
- No dosage adjustment is necessary.
- Hepatotoxicity during treatment:
- There are no dosage adjustments provided in the manufacturer's labeling; consider discontinuing therapy.
Common Side Effects of Posaconazole (Noxafil):
- Cardiovascular:
- Thrombophlebitis
- Hypertension
- Peripheral Edema
- Lower Extremity Edema
- Hypotension
- Tachycardia
- Central Nervous System:
- Headache
- Rigors
- Fatigue
- Insomnia
- Chills
- Dizziness
- Dermatologic:
- Skin Rash
- Pruritus
- Endocrine & Metabolic:
- Hypokalemia
- Hypomagnesemia
- Hyperglycemia
- Gastrointestinal:
- Diarrhea
- Nausea
- Vomiting
- Abdominal Pain
- Constipation
- Anorexia
- Stomatitis
- Decreased Appetite
- Upper Abdominal Pain
- Hematologic & Oncologic:
- Thrombocytopenia
- Anemia
- Neutropenia
- Petechia
- Hepatic:
- Increased Serum Alanine Aminotransferase
- Neuromuscular & Skeletal:
- Musculoskeletal Pain
- Arthralgia
- Respiratory:
- Cough
- Dyspnea
- Epistaxis
- Pharyngitis
- Miscellaneous:
- Fever
Rare Side Effects Of Posaconazole (Noxafil):
- Cardiovascular:
- Edema
- Pulmonary Embolism
- Torsades De Pointes
- Central Nervous System:
- Paresthesia
- Pain
- Dermatologic:
- Diaphoresis
- Endocrine & Metabolic:
- Hypocalcemia
- Adrenocortical Insufficiency
- Dehydration
- Weight Loss
- Gastrointestinal:
- Dyspepsia
- Pancreatitis
- Oral Candidiasis
- Genitourinary:
- Vaginal Hemorrhage
- Hematologic & Oncologic:
- Hemolytic-Uremic Syndrome
- Thrombotic Thrombocytopenic Purpura
- Hepatic:
- Hyperbilirubinemia
- Hepatic Insufficiency
- Hepatitis
- Hepatomegaly
- Increased Liver Enzymes
- Jaundice
- Increased Serum Aspartate Aminotransferase
- Increased Serum Alkaline Phosphatase
- Hypersensitivity:
- Hypersensitivity Reaction
- Infection:
- Herpes Simplex Infection
- Neuromuscular & Skeletal:
- Back Pain
- Asthenia
- Renal:
- Acute Renal Failure
- Respiratory:
- Pneumonia
Contraindications to Posaconazole (Noxafil):
- Hypersensitivity to posaconazole and other azole antifungal agent agents or any component of this formulation
- Concomitant therapy using sirolimus, ergotaloids (eg. ergotamine and dihydroergotamine), HMG–CoA reductase inhibits that are primarily metabolized via CYP3A4(eg. atorvastatin lovastatin simvastatin) or CYP3A4 substrats that cause QT prolongation (eg pimozide, quinidine).
Warnings and precautions
- Hepatic effects
- Posaconazole may cause transaminitis, liver dysfunction or severe reactions (cholestasis and hepatic failure, including death).
- Most liver function abnormalities can be reversed after stopping the drug. Some cases can even be resolved without interruption.
- Patients who have underlying hematologic malignancy and receive 800 mg daily suspensions are at greater risk for severe adverse reactions.
- At baseline, and every other time during therapy, liver function tests should always be performed.
- In the event of elevated liver function tests, it is necessary to monitor for severe hepatic injuries.
- If there is clinical evidence of liver disease in patients, it is best to stop the therapy.
- Arrhythmias:
- It should not be used in patients at high risk for arrhythmia (longQT syndrome, concurrent QTc prolonging drugs metabolized via CYP3A4, hypokalemia).
- It can cause QTc prolongation and torsades-de-pointes.
- An abnormality in the electrolyte:
- Prior to and during therapy, electrolyte abnormalities like hypokalemia, hypermagnesemia, and hypocalcemia must be corrected.
- Renal impairment
- It should not be used in patients who have an eGFR of 50mL/minute/1.73m2.
- Refer to "Dosage forms specific issues: Injection formula." It is important to monitor the renal function at baseline and every other week during therapy.
- If you are looking to improve your renal function, oral therapy should be administered.
- Patients with severe renal impairment who are taking delayed-release tablets, or oral suspensions due to the variability in posaconazole dose exposure should be monitored for fungal infections.
Posaconazole: Drug Interaction
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
Risk Factor C (Monitor therapy) |
|
|
Alosetron |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. |
|
Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. |
|
|
Apalutamide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apalutamide. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban. |
|
|
Posaconazole may increase the serum concentration of Atazanavir. |
|
|
Benperidol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. |
|
Benzhydrocodone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. |
|
Betamethasone (Ophthalmic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). |
|
Bictegravir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. |
|
Bortezomib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. |
|
|
Brentuximab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. |
|
|
Budesonide (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). |
|
Budesonide (Oral Inhalation |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. |
|
|
Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Busulfan. Isavuconazonium considerations are addressed in separate monographs. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. |
|
|
Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. |
|
Cannabis |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. |
|
Cinacalcet |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. |
|
CloZAPine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Codeine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. |
|
Corticosteroids (Orally Inhaled) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). |
|
Corticosteroids (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. |
|
Dexamethasone (Ophthalmic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dexamethasone (Ophthalmic). |
|
Dienogest |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. |
|
Digoxin |
Posaconazole may increase the serum concentration of Digoxin. |
|
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estazolam. |
|
|
Estrogen Derivatives |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. |
|
|
Fosamprenavir |
Posaconazole may increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Posaconazole. |
|
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. |
|
|
Gefitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. |
|
Posaconazole may enhance the hypoglycemic effect of GlipiZIDE. Posaconazole may increase the serum concentration of GlipiZIDE. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. |
|
|
Idelalisib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. |
|
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. |
|
|
Imatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. |
|
Imidafenacin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. |
|
|
Levobupivacaine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. |
|
Losartan |
Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Losartan. Applicable Isavuconazonium considerations are addressed in separate monographs. |
|
Lumefantrine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. |
|
MedroxyPROGESTERone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone. |
|
May decrease the serum concentration of Posaconazole. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. |
|
|
Nalfurafine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. |
|
|
Parecoxib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. |
|
Paricalcitol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. |
|
CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. |
|
|
Pranlukast |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. |
|
|
PrednisoLONE (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. |
|
|
Posaconazole may increase the serum concentration of Ritonavir. |
|
|
RomiDEPsin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. |
|
Sibutramine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. |
|
|
Tacrolimus (Topical) |
Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus (Topical). Applicable Isavuconazonium considerations are addressed in separate monographs. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Telithromycin. |
|
|
Tetrahydrocannabinol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. |
|
Tetrahydrocannabinol and Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. |
|
|
Upadacitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. |
|
Vilanterol |
May increase the serum concentration of CYP3A4 Inhibitors (Strong). |
|
Vitamin K Antagonists (eg, warfarin) |
Posaconazole may increase the serum concentration of Vitamin K Antagonists. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. |
|
Risk Factor D (Consider therapy modification) |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. |
|
|
Alitretinoin (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALPRAZolam. Management: Consider using an alternative agent that is less likely to interact. If combined, monitor for increased therapeutic/toxic effects of alprazolam if combined with a strong CYP3A4 inhibitor. |
|
|
Antineoplastic Agents (Vinca Alkaloids) |
Posaconazole may enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Posaconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Management: Avoid the concomitant use of posaconazole and vinca alkaloids when possible. If combined, monitor for increased vinca alkaloid toxicities (eg, neurotoxicity, gastrointestinal toxicity). |
|
ARIPiprazole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. |
|
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. |
|
|
Brexpiprazole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a moderate CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. |
|
Brigatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). |
|
Budesonide (Topical) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. |
|
|
Cabazitaxel |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. |
|
Cabozantinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. |
|
Calcium Channel Blockers |
Antifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Clevidipine. |
|
Cariprazine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. See prescribing information or full interaction monograph for details. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. |
|
|
Colchicine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. |
|
Copanlisib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. |
|
CycloSPORINE (Systemic) |
Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). Fluconazole and isavuconazonium considerations are addressed in separate monographs. |
|
CycloSPORINE (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of CycloSPORINE (Systemic). |
|
CYP3A4 Substrates (High risk with Inhibitors) |
CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); AmLODIPine; Benzhydrocodone; Buprenorphine; Gefitinib; HYDROcodone; Mirtazapine; Praziquantel; Telithromycin; Vinorelbine. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat. |
|
|
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. |
|
|
May decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. |
|
|
DOXOrubicin (Conventional) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. |
|
Drospirenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Management: Drospirenone use is contraindicated specifically when the strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. |
|
|
Eliglustat |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). |
|
|
Etizolam |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely. |
|
Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Applicable Isavuconazonium considerations are addressed in separate monographs. Etravirine may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Etravirine may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with voriconazole. Management: Monitor for increased effects/toxicity of etravirine. Antifungal dose adjustment may be needed for ketoconazole, itraconazole, or posaconazole but specific dosing guidelines are lacking. |
|
|
Fedratinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. |
|
FentaNYL |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. |
|
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. |
|
|
Fluticasone (Oral Inhalation) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Monitor patients using such a combination more closely. |
|
May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Fosphenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. |
|
|
Histamine H2 Receptor Antagonists |
May decrease the serum concentration of Posaconazole. Management: Avoid concurrent use of oral suspension with H2-antagonists whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Delayedrelease posaconazole tablets may be less likely to interact. |
|
Posaconazole may increase the serum concentration of Ibrutinib. Management: Ibrutinib dose reductions are required when combined with posaconazole. Dose recommendations depend on the indication for ibrutinib and the posaconazole dose. See full monograph for details. |
|
|
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for specific age- and weight-based recommendations. |
|
|
Ixabepilone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor half-life. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80 mg/day in patients also receiving strong CYP3A4 inhibitors. |
|
|
Lorlatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. |
|
Manidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. Management: Consider reducing meperidine dose if concomitant use with strong CYP3A4 inhibitors is required. Monitor for signs and symptoms of respiratory depression and sedation when these agents are combined. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related adverse effects. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 600 mg/day when combined with a strong CYP3A4 inhibitor. Monitor for increased mifepristone toxicity regardless of dose or indication. |
|
|
Mirodenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 100 mg twice daily. |
|
|
CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PAZOPanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib adult dose to 400 mg. Further dose reductions may also be required. |
|
|
Pexidartinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg/day to 200 mg/day. |
|
Phenytoin |
Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs. Phenytoin may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Concomitant therapy with itraconazole, voriconazole, or ketoconazole and phenytoin should probably be avoided, as antifungal failure is likely. Consider selecting alternative antifungal therapy. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. |
|
|
Piperaquine |
CYP3A4 Inhibitors (Strong) may enhance the QTc-prolonging effect of Piperaquine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Management: Avoid concomitant use of piperaquine and strong CYP3A4 inhibitors when possible. If the combination cannot be avoided, frequent ECG monitoring is recommended due to the risk for QTc prolongation. Exceptions are discussed separately. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. |
|
|
Proton Pump Inhibitors |
May decrease the serum concentration of Posaconazole. |
|
Reboxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. |
|
Rifamycin Derivatives |
Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Saxagliptin U.S. product labeling recommends limiting saxagliptin adult dose to 2.5 mg/day when used with a strong CYP3A4 inhibitor. Monitor for increased saxagliptin levels/effects. A similar recommendation is not made in the Canadian product labeling. |
|
|
Posaconazole may increase the serum concentration of Sildenafil. Management: Concurrent posaconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent posaconazole. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Solifenacin. Management: Limit solifenacin doses to 5 mg daily when combined with strong CYP3A4 inhibitors. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, sunitinib dose decreases are recommended, and vary by indication. See full monograph for details. |
|
|
Tacrolimus (Systemic) |
Posaconazole may increase the serum concentration of Tacrolimus (Systemic). Management: Reduce tacrolimus dose to approximately one-third of original dose when starting posaconazole. Tacrolimus blood concentrations should be monitored closely during and at discontinuation of posaconazole. |
|
Posaconazole may increase the serum concentration of Tadalafil. |
|
|
Posaconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to posaconazole. Monitor sirolimus concentrations in all patients receiving posaconazole or any systemic azole antifungal. |
|
|
Tezacaftor |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor. Management: When combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor alone should be administered. |
|
Thiotepa |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full monograph for details. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. |
|
|
Toremifene |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Exceptions are discussed in separate monograph. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. |
|
|
Posaconazole may increase the serum concentration of Vardenafil. Management: Limit vardenafil dosing to a maximum of 2.5 mg per 24 hours in patients receiving concurrent therapy with strong CYP3A4 inhibitors, such as posaconazole. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with strong CYP3A4 inhibitors when possible. Consider use of an alternative that is not a strong inhibitor of CYP3A4 as clinically appropriate. Exceptions are discussed in separate monographs. |
|
|
Posaconazole may increase the serum concentration of Venetoclax. Management: This combination is contraindicated during venetoclax initiation and ramp-up in patients with CLL/SLL. Reduced venetoclax doses are required during ramp-up for patients with AML, and reduced doses are required for all patients during maintenance therapy. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. |
|
Risk Factor X (Avoid combination) |
|
|
Acalabrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. |
|
Ado-Trastuzumab Emtansine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. |
|
|
Astemizole |
Posaconazole may increase the serum concentration of Astemizole. |
|
Asunaprevir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. |
|
AtorvaSTATin |
Posaconazole may increase the serum concentration of AtorvaSTATin. |
|
Avanafil |
Posaconazole may increase the serum concentration of Avanafil. |
|
Axitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. |
|
Barnidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. |
|
Blonanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. |
|
Bosutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. |
|
|
Budesonide (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). |
|
Posaconazole may increase the serum concentration of Cisapride. |
|
|
Cobimetinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. |
|
Conivaptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. |
|
Dabrafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. |
|
Dapoxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. |
|
Posaconazole may increase the serum concentration of Dihydroergotamine. |
|
|
Posaconazole may increase the serum concentration of Dofetilide. |
|
|
Domperidone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
|
May decrease the serum concentration of Posaconazole. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. |
|
|
Posaconazole may increase the serum concentration of Eplerenone. |
|
|
Ergoloid Mesylates |
Posaconazole may increase the serum concentration of Ergoloid Mesylates. |
|
Posaconazole may increase the serum concentration of Ergonovine. |
|
|
Posaconazole may increase the serum concentration of Ergotamine. |
|
|
Everolimus |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. |
|
|
Fluticasone (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. |
|
|
Halofantrine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Irinotecan Products |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. |
|
Isavuconazonium Sulfate |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. |
|
|
Lapatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. |
|
|
Lercanidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. |
|
Lomitapide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. |
|
Lovastatin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. |
|
Lumacaftor |
May decrease the serum concentration of Posaconazole. |
|
Lurasidone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. |
|
|
Posaconazole may enhance the QTc-prolonging effect of Methadone. Posaconazole may increase the serum concentration of Methadone. |
|
|
Posaconazole may increase the serum concentration of Methylergonovine. |
|
|
Mizolastine |
Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Mizolastine. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. |
|
|
Pimozide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. |
|
QT-prolonging CYP3A4 Substrates |
Posaconazole may increase the serum concentration of QTprolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. |
|
Posaconazole may increase the serum concentration of QuiNIDine. |
|
|
Radotinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. |
|
Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Ranolazine. Fluconazole and isavuconazonium considerations are addressed in separate monographs. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. |
|
|
Red Yeast Rice |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. |
|
|
Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. |
|
|
Posaconazole may increase the serum concentration of Sirolimus. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. |
|
|
Terfenadine |
Posaconazole may increase the serum concentration of Terfenadine. |
|
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. |
|
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. |
|
|
Udenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. |
|
Ulipristal |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. |
|
VinCRIStine (Liposomal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). |
|
Vinflunine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. |
|
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. |
|
Monitoring parameters:
- CBC
- LFTs (eg, AST/ALT, alkaline phosphatase, and bilirubin) prior to initiation and during treatment.
- RFTs, especially in patients on IV therapy if eGFR <50 mL/minute/1.73 m²
- Serum electrolytes (eg, calcium, magnesium, potassium) before and during therapy
- For invasive aspergillosis (treatment or prolonged prophylaxis), IDSA recommends monitoring serum trough concentrations in patients receiving posaconazole oral suspension; further studies are needed to address whether therapeutic drug monitoring is helpful or necessary with delayed-release tablets or IV formulations of posaconazole.
- In general, evidence to support therapeutic drug monitoring for posaconazole is limited; however, due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions with posaconazole, therapeutic drug monitoring is advised.
How to administer Posaconazole (Noxafil)?
Oral:
- Suspension:
- Shake well before use.
- It should be given with provided measured dosing spoon during or within 20 minutes after a full meal.
- Patients who are unable to eat a full meal may take each dose with an oral liquid nutritional supplement or acidic carbonated beverage (eg, ginger ale).
- In patients unable to eat a full meal or tolerate a liquid nutritional supplement or acidic carbonated beverage and who do not have the option of taking the delayed-release tablet or injection, an alternative antifungal should be given.
- Tablets (delayed-release):
- Tablets should be swallowed as a whole with food without crushing, dissolving, chewing, or dividing.
- Patients with severe diarrhea or vomiting should be monitored for breakthrough fungal infections.
IV:
- It should be given via a central venous line over 90 minutes.
- It should not be given as an IV push or bolus.
- Must be infused through an in-line filter (0.22-micron polyethersulfone [PES] or polyvinylidene difluoride [PVDF]).
- Infusion through a peripheral line should only be used as a one-time infusion over 30 minutes in a patient who will be receiving a central venous line for subsequent doses or to bridge a period during which a central venous line is to be replaced or is in use for another infusion.
- Maybe an irritant.
Note: In clinical trials, infusion site reactions occurred when multiple peripheral infusions given through the same vein.
Mechanism of action of Posaconazole (Noxafil):
Posaconazole leads to decreased ergosterol synthesis (principal sterol in the fungal cell membrane), inhibits fungal cell membrane formation by interfering with fungal cytochrome P450 (lanosterol-14a-demethylase).
Absorption:
- Oral suspension:
- Unpredictable and variable (optimal absorption with a high-fat meal in 4 divided doses; absorption may be sufficient if taken with a nutritional supplement or acidic beverage [eg, ginger ale]).
- Tablet (delayed-release):
- Predictable (preferably administered with food, but absorption is sufficient under fasting conditions).
Protein binding:
- >98%;
- predominantly bound to albumin
Metabolism:
- Not significantly metabolized;
- 17% undergoes non-CYP-mediated metabolism, primarily via hepatic glucuronidation into metabolites
Bioavailability:
- Oral: Suspension and delayed-release tablets are not bioequivalent; higher plasma exposure observed with delayed-release tablets
- Suspension: Dependent upon gastric pH environment (decreased with higher pH or increased motility) and fed-conditions (increased in the high-fat environment)
- Delayed-release tablets:
- Dependent upon fed condition: Fasted conditions: 54%; higher under high-fat-fed conditions (51% increase in AUC)
Half-life elimination:
- Suspension: 35 hours (range: 20 to 66 hours);
- Tablets: 26 to 31 hours; Injection: ~27 hours
Time to peak, plasma:
- Suspension: ~3 to 5 hours;
- Tablets: ~4 to 5 hours
Excretion:
- Feces 71% (~66% of the total dose as unchanged drug);
- urine 13% (<0.2% of the total dose as unchanged drug)
International Brand Names of Posaconazole:
- Noxafil
- Posanol
- Asperonazol
- Noxafil EC
- Posanol
- Spirafil
- Zolafungi
Posaconazole Brand Names in Pakistan:
No Brands Available in Pakistan.
.png)
