Posaconazole is an antifungal medication that belongs to the class of drugs known as triazole antifungals. It is used to treat a variety of fungal infections, particularly in patients who have weakened immune systems.
Posaconazole works by inhibiting the growth and spread of various fungi by interfering with the synthesis of ergosterol, an essential component of fungal cell membranes. By disrupting the integrity of the cell membrane, posaconazole effectively kills or inhibits the growth of the fungi.
Indications of Posaconazole (Noxafil):
- Candidiasis, oropharyngeal:
- Suspension (≥13 years of age):
- Oropharyngeal candidiasis can be successfully treated with it, even in patients who are resistant to itraconazole and/or fluconazole.
- Suspension (≥13 years of age):
- Invasive fungal infections, prophylaxis:
- injections, delayed-release tablets (for those over 18), and suspensions (for those under 13):
- 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).
- injections, delayed-release tablets (for those over 18), and suspensions (for those under 13):
- 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:
- Posaconazole is a medication used to treat fungal infections in people with weak immune systems. It comes in different forms, like delayed-release tablets, oral suspension, and intravenous (IV) injection.
- The delayed-release tablet and oral suspension should not be used interchangeably because they have different dosing instructions. The delayed-release tablet is easier to take, better tolerated, and absorbed more consistently. So, doctors prefer prescribing the delayed-release tablet.
- Studies have shown that a once-daily 300 mg dose of the delayed-release tablet has similar or greater effectiveness compared to taking 200 mg of the medication 3 to 4 times a day. This information is based on how the medication is absorbed and processed in the body (pharmacokinetics).
- The IV formulation of posaconazole is given at the same dose as the delayed-release tablet. This means that the amount of medication delivered through the IV is equivalent to taking the delayed-release tablet.
Posaconazole (Noxafil) treatment dose of invasive Aspergillosis:
In the treatment of invasive Aspergillosis, the dosing of posaconazole varies depending on the specific situation:
Prophylaxis in immunocompromised patients:
- Oral Suspension: Take 200 mg three times daily. The duration of therapy is based on the recovery from neutropenia or immunosuppression.
- Tablet (delayed release): On the first day, take 300 mg twice daily, followed by 300 mg once daily from the second day onwards. The duration of therapy is based on the recovery from neutropenia or immunosuppression.
Patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS):
- For patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS), posaconazole is typically initiated at the start of chemotherapy or 24 hours after the last anthracycline dose.
- It is continued until recovery from neutropenia, complete remission, or for up to 12 weeks, whichever occurs first.
Patients with graft-versus-host disease (GVHD):
- In patients with graft-versus-host disease (GVHD) receiving immunosuppressive therapy, posaconazole is usually continued for 112 days.
- However, the optimal duration in GVHD has not been fully defined.
- It is generally recommended to continue posaconazole throughout the duration of immunosuppression.
Missed dose:
- Missed doses should be taken as soon as remembered, unless it is less than 12 hours until the next dose.
- In that case, the missed dose should be skipped, and the regular schedule should be resumed.
- Doubling the doses should be avoided.
For the treatment of refractory Aspergillosis (when other therapies have not been effective or are not tolerated), the following dosing regimens may be used:
- Oral Suspension: Take 200 mg three times daily or 200 mg four times daily. For outpatients, a switch to 400 mg twice daily may be considered.
- Tablet (delayed release): On the first day, take 300 mg twice daily, followed by 300 mg once daily for maintenance.
Intravenous (IV) administration follows a similar dosing regimen:
- Loading dose: 300 mg twice daily on the first day.
- Maintenance dose: 300 mg once daily from the second day onwards.
Duration of therapy:
- The duration of therapy for invasive Aspergillosis is typically a minimum of 6 to 12 weeks.
- However, the duration can vary depending on the degree and duration of immunosuppression, the site of the disease, and the evidence of disease improvement.
Posaconazole (Noxafil) dose in the treatment of Candidiasis:
Prophylaxis in immunocompromised patients with disseminated candidiasis:
- Oral Suspension: Take 200 mg three times daily. The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Tablet (delayed release): On the first day, take 300 mg twice daily. From the second day onwards, take 300 mg once daily. The duration of therapy is based on recovery from neutropenia or immunosuppression.
Missed Dose:
- For missed doses, take the missed dose as soon as remembered.
- However, if it is less than 12 hours until the next dose, skip the missed dose and resume the regular schedule.
- Doubling the doses should be avoided.
Intravenous (IV) administration follows a similar dosing regimen:
- Initial dose: 300 mg twice daily on the first day.
- Maintenance dose: 300 mg once daily from the second day onwards. The duration of therapy is based on recovery from neutropenia or immunosuppression.
For the treatment of Candidiasis, the dosing regimens are as follows:
- Oropharyngeal infection:
- Oral Suspension: On the first day, take 100 mg twice daily. From the second day onwards, take 100 mg once daily for a total of 13 days.
- Refractory oropharyngeal infection (not responding to fluconazole):
- Oral Suspension: Take 400 mg twice daily for 3 days, then 400 mg once daily for up to 28 days.
- In HIV-infected patients (as an alternative to fluconazole or in cases where fluconazole is not effective):
- Oral Suspension: On the first day, take 400 mg twice daily. From the second day onwards, take 400 mg once daily for 7 to 14 days for initial episodes. In azole-refractory patients, continue for 28 days.
Posaconazole (Noxafil) dose in the treatment of Esophageal infections (off-label):
In the treatment of esophageal infections, posaconazole can be used as an off-label therapy, particularly in cases where fluconazole has been ineffective (refractory) or in HIV-infected patients who are unresponsive to azole medications. The dosing regimens are as follows:
Fluconazole-refractory esophageal infections (alternate therapy):
- Tablet (delayed-release): Take 300 mg once daily.
- Suspension: Take 400 mg twice daily.
For HIV-infected patients who are unresponsive to azole medications:
- Suspension: Take 400 mg twice daily for 28 days.
- If the patient experiences frequent or severe recurrences, posaconazole may be continued for suppressive therapy.
- However, it is recommended to consider discontinuing suppressive therapy when the patient's CD4 count is greater than 200/mm3.
Posaconazole (Noxafil) dose in the treatment of Coccidioidomycosis (refractory to conventional therapy) (off-label):
Nonmeningeal infection:
- Tablet (delayed-release): On the first day, take 300 mg twice daily. From the second day onwards, take 300 mg once daily.
- Suspension: Take 400 mg twice daily.
Duration of therapy
- The duration of therapy for Coccidioidomycosis varies depending on the site and severity of the infection, as well as the patient's immune status.
- The specific duration should be determined by the healthcare provider based on individual factors.
Posaconazole (Noxafil) dose in the treatment of Meningeal infection:
- Tablet (delayed-release): On the first day, take 300 mg twice daily. From the second day onwards, take 300 mg once daily for maintenance. Some experts recommend a higher maintenance dose of 200 to 300 mg twice daily, with routine therapeutic drug monitoring.
- Suspension: Take either 200 mg four times daily or 400 mg twice daily.
It's also worth mentioning that the use of posaconazole for meningeal infections is considered off-label, meaning it is not specifically approved by regulatory authorities for this particular indication. However, it may be considered as an alternative therapy in cases where conventional treatments have not been effective.
Duration of therapy:
- In the treatment of meningeal infections with posaconazole, it is recommended to continue therapy lifelong due to the high relapse rate when the dose is decreased or treatment is discontinued.
- This recommendation is supported by guidelines from the Department of Health and Human Services (HHS) and the Infectious Diseases Society of America (IDSA).
- The goal of lifelong therapy is to maintain control of the infection and prevent relapse.
Posaconazole (Noxafil) dose in the treatment of Cryptococcal infections (off-label):
In the treatment of Cryptococcal infections, posaconazole can be used off-label. The dosing regimens are as follows:
Pulmonary Cryptococcal infection in non-immunosuppressed individuals (as an alternative agent):
- Oral Suspension: Take 400 mg twice daily.
Salvage treatment of relapsed infection:
- Oral Suspension: Take 400 mg twice daily (or 200 mg four times daily) for a duration of 10 to 12 weeks. It's important to note that salvage treatment should only be initiated after completing an appropriate course of an induction regimen.
Please be aware that the use of posaconazole for Cryptococcal infections is considered off-label, which means it is not specifically approved for this particular indication. The dosing recommendations provided here are based on available evidence and clinical experience.
Posaconazole (Noxafil) dose in the treatment of Mucormycosis, salvage and step-down therapy (off-label):
In the treatment of Mucormycosis, both salvage therapy and step-down therapy can involve the use of posaconazole, although it is considered off-label for this indication. The dosing regimens are as follows:
Salvage and step-down therapy:
- Oral Suspension: Take 800 mg per day, divided into 2 or 4 doses.
- Tablet (delayed-release): On the first day, take 300 mg twice daily. From the second day onwards, take 300 mg once daily for maintenance.
- IV: On the first day, take 300 mg every 12 hours. From the second day onwards, take 300 mg every 24 hours for maintenance.
Duration of therapy:
- The duration of therapy for Mucormycosis varies based on the individual's clinical and radiologic response, as well as their immunocompetence.
- It is important to consult with a healthcare professional for personalized advice and guidance regarding the appropriate duration of treatment.
Please note that the use of posaconazole for Mucormycosis is considered off-label, meaning it is not specifically approved for this indication. The dosing recommendations provided here are based on available evidence and expert guidelines.
Posaconazole (Noxafil) dose in children:
Note:
- The correct dosage form should be verified.
- It is not advised to switch between the oral suspension and the delayed-release tablet.
Posaconazole (Noxafil) dose in HSCT recipients for antifungal prophylaxis: Limited data available:
In the prophylaxis of antifungal infections in hematopoietic stem cell transplant (HSCT) recipients, posaconazole dosing varies based on age groups. Here are the recommended dosing regimens:
Infants aged 8 months and children under 12 years:
- Oral suspension: Take 4 mg/kg/dose three times daily.
- Begin 2-4 days prior to discharge and continue until either day 100 post-HSCT or until CD4 T cells reach 200/mm3 and CD8 cells reach 100/mm3, whichever is longer.
- The dosing is based on experience in 60 pediatric patients, with a median age of 6 years (age range: 0.7-11.5 years).
- Pharmacokinetic analysis showed that a total daily dose of 12 mg/kg (4 mg/kg three times daily) produced morning serum trough concentrations similar to effective adult values.
- The evaluated regimen of 10 mg/kg/day (5 mg/kg twice daily) produced lower morning trough levels and was subsequently removed from the protocol.
- Overall, no patients developed invasive mycosis, and no severe adverse effects were observed. The median duration of therapy was 127 days (range: 12-188 days).
Adolescents aged 13 years and older:
- Oral suspension: Take 200 mg three times daily.
- Begin with graft-versus-host disease (GVHD) diagnosis and continue until GVHD resolves.
Posaconazole (Noxafil) Dose for antifungal prophylaxis in acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS):
In the prophylaxis of antifungal infections in adolescents (aged 13 years and older) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), posaconazole dosing recommendations are as follows:
- Oral suspension: Take 200 mg three times daily.
- This dosing regimen is intended to be used during chemotherapy-associated neutropenia.
- Consider using posaconazole in centers with a high incidence of mold infections or when fluconazole is not available.
Please note that the dosing information provided is based on limited available data and specific considerations for AML or MDS patients. It is important to consult with a healthcare professional for personalized advice and guidance regarding the use of posaconazole for antifungal prophylaxis in this population.
Factors such as the patient's age, weight, underlying conditions, and any specific patient characteristics should be taken into account when determining the appropriate dosing regimen.
Posaconazole (Noxafil) Dose in the prophylaxis of invasive Aspergillosis:
In the prophylaxis of invasive Aspergillosis, the recommended posaconazole dosing regimens are as follows:
Adolescents aged 13 years and older:
- Preferred: Oral delayed-release tablets
- Initial dose: 300 mg twice daily for one day.
- Maintenance dose: 300 mg once daily starting on Day 2.
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses: Take the missed dose as soon as remembered. If it is less than 12 hours until the next dose, skip the missed dose and return to the regular schedule. Do not double doses.
- Alternative: Oral suspension
- Dose: 200 mg three times daily.
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses: Take the missed dose as soon as remembered. If it is less than 12 hours until the next dose, skip the missed dose and return to the regular schedule. Do not double doses.
Intravenous (IV) Administration:
- Adolescents aged 18 years and older:
- Loading dose: 300 mg twice daily on day 1.
- Maintenance dose: 300 mg once daily starting on day 2 and thereafter.
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
Posaconazole (Noxafil) Treatment dose of Candidiasis:
In the treatment of Candidiasis, the recommended posaconazole dosing regimens are as follows:
Esophageal Infection (Azole-Refractory, HIV-Exposed/-Positive):
- Treatment: Adolescent:
- Oral suspension: 400 mg twice daily for 28 days.
- Note: If the patient experiences frequent or severe recurrences, posaconazole may be continued for suppressive therapy. Consider discontinuing when CD4 count is >200/mm³ (DHHS [adult], 2014).
Invasive Infections:
- Prophylaxis: Adolescents aged 13 years and older:
- Preferred: Oral delayed-release tablets
- Initial dose: 300 mg twice daily for one day.
- Maintenance dose: 300 mg once daily.
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses: Take the missed dose as soon as remembered. If it is less than 12 hours until the next dose, skip the missed dose and return to the regular schedule. Do not double doses.
- Alternative: Oral suspension
- Dose: 200 mg three times daily.
- The duration of therapy is based on recovery from neutropenia or immunosuppression.
- Missed doses: Take the missed dose as soon as remembered. If it is less than 12 hours until the next dose, skip the missed dose and return to the regular schedule. Do not double doses.
- Preferred: Oral delayed-release tablets
Treatment of Refractory Infection:
- Limited data available for children aged 8 years and older and adolescents:
- Oral suspension: 800 mg/day administered as either 200 mg four 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 (Krishna, 2007).
Posaconazole (Noxafil) Treatment dose of Oropharyngeal infection:
Non-HIV-Exposed/-Positive:
- Adolescents aged 13 years and older:
- Treatment:
- Oral suspension:
- Initial dose: 100 mg twice daily on day 1.
- Maintenance dose: 100 mg once daily for 13 days.
- Oral suspension:
- Treatment:
Refractory Infection:
- Adolescents aged 13 years and older:
- Treatment:
- Oral suspension: 400 mg twice daily.
- The duration of therapy is based on the underlying disease and clinical response.
- Treatment:
HIV-Exposed/-Positive:
- Adolescents:
- Treatment:
- Oral suspension:
- Initial dose: 400 mg twice daily on day 1.
- Maintenance dose: 400 mg once daily for 28 days (DHHS [adult], 2014).
- Oral suspension:
- Treatment:
Posaconazole (Noxafil) Pregnancy Risk Category: B3
- In studies conducted on animals, some negative effects on reproduction have been observed.
Posaconazole use during breastfeeding:
- It is uncertain whether posaconazole is found in breast milk.
- The manufacturer recommends carefully considering the potential risks of infant exposure, the benefits of breastfeeding for the baby, and the advantages of the treatment for the mother when making a decision about breastfeeding during therapy.
Posaconazole (Noxafil) Dose adjustment in kidney disease:
Delayed-release tablets and oral suspension:
- For delayed-release tablets and oral suspension of posaconazole, no dosage adjustment is necessary for individuals with an estimated glomerular filtration rate (eGFR) between 20 and 80 mL/minute/1.73 m².
- For individuals with an eGFR less than 20 mL/minute/1.73 m², no dosage adjustment is required; however, it is important to monitor for breakthrough fungal infections due to variability in posaconazole exposure.
IV infusion:
- Regarding the intravenous (IV) infusion form of posaconazole, no dosage adjustment is necessary for individuals with an eGFR greater than or equal to 50 mL/minute/1.73 m².
- For individuals with an eGFR less than 50 mL/minute/1.73 m², it is recommended to avoid the use of IV posaconazole unless the risk and benefit have been assessed, as the intravenous vehicle (cyclodextrin) may accumulate.
- Serum creatinine levels should be monitored, and if increases occur, considering switching to oral therapy may be appropriate.
Posaconazole (Noxafil) Dose adjustment in liver disease:
- For individuals with preexisting mild-to-severe liver impairment (Child-Pugh class A, B, or C), no dosage adjustment is necessary for posaconazole.
- In case hepatotoxicity (liver damage) occurs during treatment, the manufacturer's labeling does not specify any dosage adjustments. In such situations, it is recommended to 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):
- Posaconazole should not be coadministered with sirolimus, ergot alkaloids (such as ergotamine and dihydroergotamine), HMG-CoA reductase inhibitors that are mainly metabolized by CYP3A4 (such as atorvastatin, lovastatin, and simvastatin), or CYP3A4 substrates that can prolong the QT interval (such as pimozide and quinidine).
- It should also be avoided in individuals who have a hypersensitivity or allergic reaction to posaconazole, other azole antifungal agents, or any component of the posaconazole formulation.
Warnings and precautions
Hepatic effects
- Posaconazole can cause liver dysfunction, which can range from mild to severe.
- This may manifest as increases in liver function tests such as ALT, AST, alkaline phosphatase, and total bilirubin, as well as clinical hepatitis.
- In some cases, the liver effects can be severe, leading to cholestasis, hepatic failure, and even death.
- The elevation in liver function tests is generally reversible after discontinuing posaconazole, and some cases have resolved without stopping the medication.
- Patients with serious underlying medical conditions, particularly hematologic malignancies, are more prone to experiencing severe hepatic reactions, especially when taking high doses of the suspension (800 mg daily).
- It is important to monitor liver function tests before starting posaconazole and regularly during treatment.
- If there are significant increases in liver function tests or signs of liver disease, posaconazole should be discontinued.
Arrhythmias:
- Special caution should be exercised when prescribing posaconazole to patients who have an increased risk of arrhythmias.
- This includes individuals with conditions such as long QT syndrome, those taking medications that prolong the QT interval and are metabolized through CYP3A4, as well as patients with hypokalemia (low potassium levels).
- It has been reported that posaconazole can lead to QTc prolongation, which is a measurement of the electrical activity of the heart, and in some cases, it can result in a serious arrhythmia called torsades de pointes.
- Therefore, close monitoring of cardiac function is important during treatment with posaconazole, especially in patients with these risk factors.
An abnormality in the electrolyte:
- It is important to address any existing electrolyte abnormalities, such as low levels of potassium, magnesium, or calcium, before starting treatment with posaconazole.
- These electrolyte imbalances should also be monitored and corrected as needed during therapy.
- Maintaining proper electrolyte balance is essential for the optimal functioning of various bodily processes, and addressing any deficiencies can help support the effectiveness and safety of posaconazole treatment.
Renal impairment
- In patients with renal impairment, caution should be exercised when using posaconazole.
- The injection formulation should not be used in patients with an estimated glomerular filtration rate (eGFR) of less than 50 mL/minute/1.73 m², unless the potential benefits outweigh the risks and have been assessed by a healthcare professional.
- Renal function, including serum creatinine levels, should be evaluated before starting therapy and regularly monitored during treatment.
- If there are increases in serum creatinine, consideration may be given to switching to oral therapy.
- It is important to closely monitor patients with severe renal impairment who are taking delayed-release tablets or oral suspension for breakthrough fungal infections, as there may be variations in posaconazole exposure in this population.
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
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Risk Factor C (Monitor therapy) |
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Alosetron |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. |
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Amphotericin B's therapeutic efficacy may be reduced by antifungal agents (systemic azole derivatives). |
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Apalutamide |
The serum concentration of apalutamide may rise in response to CYP3A4 Inhibitors (Strong). |
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The serum levels of apixaban may rise in response to CYP3A4 Inhibitors (Strong). |
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Atazanavir's serum concentration might be raised by posaconazole. |
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Benperidol |
The serum concentration of Benperidol may rise in response to CYP3A4 Inhibitors (Strong). |
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Benzhydrocodone |
The serum levels of Benzhydrocodone may rise in response to CYP3A4 Inhibitors (Strong). In particular, there might be an increase in hydrocodone concentration. |
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Betamethasone (Ophthalmic) |
Betamethasone serum levels may rise in response to strong CYP3A4 inhibitors (Ophthalmic). |
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Bictegravir |
Bictegravir's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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Bortezomib |
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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. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. |
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Budesonide (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). |
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Budesonide (Oral Inhalation |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. |
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The serum levels of busulfan may rise in response to antifungal agents (systemic azole derivatives). Separate monographs address isavuconazonium considerations. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. |
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Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. |
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Cannabis |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. |
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Cinacalcet |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. |
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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. |
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Codeine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. |
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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). |
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Corticosteroids (Systemic) |
Corticosteroids may be present in greater amounts in the serum while taking strong CYP3A4 inhibitors (Systemic). MethylPREDNISolone, PrednisoLONE (Systemic), and PredniSONE are exceptions. |
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Dexamethasone (Ophthalmic) |
Dexamethasone serum levels may rise in response to strong CYP3A4 inhibitors (Ophthalmic). |
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Dienogest |
The serum concentration of Dienogest may rise in response to CYP3A4 Inhibitors (Strong). |
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Digoxin |
Posaconazole may raise the level of Digoxin in the blood. |
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CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estazolam. |
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Estrogen Derivatives |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. |
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Fosamprenavir |
The active metabolite(s) of fosamprenavir's serum concentrations may rise in response to posaconazole. Posaconazole's serum levels may drop if you take fosamprenavir. |
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The active metabolite(s) of foamamatinib may be present in higher serum quantities while taking CYP3A4 Inhibitors (Strong). |
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Galantamine's serum levels may rise in response to strong CYP3A4 inhibitors. |
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Gefitinib |
It's possible that CYP3A4 Inhibitors (Strong) will raise the level of gefitinib in the blood. |
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Posaconazole might improve GlipiZIDE's hypoglycemic effects. Posaconazole may raise GlipiZIDE's serum levels. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. |
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Idelalisib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. |
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CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. |
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Imatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. |
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Imidafenacin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. |
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Levobupivacaine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. |
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Losartan |
Losartan's metabolism may be slowed down by antifungal agents (systemic azole derivatives). In separate monographs, relevant Isavuconazonium concerns are covered. |
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Lumefantrine |
Lumefantrine's serum levels may rise when taken with CYP3A4 Inhibitors (Strong). |
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MedroxyPROGESTERone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone. |
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May decrease the serum concentration of Posaconazole. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. |
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Nalfurafine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. |
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Parecoxib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. |
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Paricalcitol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. |
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CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. |
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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. |
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Pranlukast |
Pranlukast's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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Praziquantel's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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PrednisoLONE (Systemic) |
PrednisoLONE serum levels may rise in response to strong CYP3A4 inhibitors (Systemic). |
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PredniSONE's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong). |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. |
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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. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. |
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Ritonavir's serum levels can rise in response to posaconazole. |
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RomiDEPsin |
RomiDEPsin's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. |
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Tacrolimus (Topical) |
Tacrolimus metabolism may be decreased by systemic azole derivative antifungal agents (Topical). In separate monographs, relevant Isavuconazonium concerns are covered. |
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Tasimelteon's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong). |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Telithromycin. |
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Tetrahydrocannabinol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. |
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Tetrahydrocannabinol and Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. |
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Upadacitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. |
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Vilanterol |
May increase the serum concentration of CYP3A4 Inhibitors (Strong). |
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Vitamin K Antagonists (eg, warfarin) |
The serum concentration of Vitamin K antagonists may rise in response to posaconazole. |
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Zolpidem's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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Risk Factor D (Consider therapy modification) |
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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. |
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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. |
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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. |
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The serum levels of ALPRAZolam may rise in response to CYP3A4 Inhibitors (Strong). Management: Take into account utilising a different agent that interacts less frequently. If coupled, keep an eye out for alprazolam's potentially hazardous or increased therapeutic effects. |
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Antineoplastic Agents (Vinca Alkaloids) |
Posaconazole might make antineoplastic agents more harmful or hazardous (Vinca Alkaloids). The serum concentration of antineoplastic agents may rise when taking posaconazole (Vinca Alkaloids). Management: Whenever feasible, avoid using posaconazole and vinca alkaloids concurrently. Watch out for increased vinca alkaloid toxicity if combined (eg, neurotoxicity, gastrointestinal toxicity). |
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ARIPiprazole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. |
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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. |
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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. |
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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). |
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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. |
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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. |
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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. |
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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. |
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Calcium Channel Blockers |
Calcium channel blockers' negative/toxic effects may be increased by antifungal agents (systemic azole derivatives). In particular, itraconazole may make verapamil or diltiazem's unfavourable inotropic effects worse. Calcium Channel Blockers' metabolism may be slowed down by antifungal agents (systemic azole derivatives). Fluconazole and isavuconazonium, which are covered in different monographs, probably have less powerful effects than those of other azoles. Treatment: Itraconazole should not be used concurrently with felodipine or nisoldipine. With any such combination, regular monitoring is advised; calcium channel blocker dose decreases might be necessary. Clevidipine is an exception. |
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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. |
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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. |
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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. |
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Copanlisib |
The serum levels of Copanlisib may rise in response to strong CYP3A4 inhibitors. Treatment: Reduce the dose of copanlisib to 45 mg if concurrent usage with potent CYP3A4 inhibitors cannot be avoided. Watch out for increasing copanlisib side effects or toxicities in your patients. |
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CycloSPORINE (Systemic) |
Systemic azole derivative antifungal agents may slow down cycloSPORINE metabolism (Systemic). Considerations related to fluconazole and isavuconazonium are covered in different monographs. |
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CycloSPORINE (Systemic) |
Strong CYP3A4 Inhibitors may raise CycloSPORINE levels in the blood (Systemic). |
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CYP3A4 Substrates (High risk with Inhibitors) |
The metabolism of CYP3A4 Substrates may be reduced by strong CYP3A4 Inhibitors (High risk with Inhibitors). Alitretinoin (Systemic), Amlopidine, Benzhydrocodone, Buprenorphine, Gefitinib, Hydrocodone, Mirtazapine, Praziquantel, Telithromycin, and Vinorelbine are exceptions. |
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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. |
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The blood concentrations of the active metabolite(s) of Deflazacort may rise in response to CYP3A4 Inhibitors (Strong). When taking deflazacort with a strong or moderate CYP3A4 inhibitor, only take one-third of the prescribed dose. |
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Could reduce how well antifungal agents are absorbed (Azole Derivatives, Systemic). Didanosine capsules with an enteric coating shouldn't have any impact on these antifungals. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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). |
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Eszopiclone's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong). When used with potent CYP3A4 inhibitors, the dose of eszopiclone should be restricted to 2 mg per day. Eszopiclone effects and toxicities should also be closely monitored (eg, somnolence, drowsiness, CNS depression). |
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Etizolam |
The serum levels of Etizolam may rise when using CYP3A4 Inhibitors (Strong). Management: If using this combination, think about utilising lower etizolam doses; there are no precise guidelines for dose reduction. Keep a watchful eye on the combination's clinical reaction. |
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Azole derivatives used systemically as antifungal agents may raise etravirine levels in the blood. In separate monographs, relevant Isavuconazonium concerns are covered. Etravirine may lower the level of antifungal agents in the serum (Azole Derivatives, Systemic). With itraconazole or ketoconazole, this could be anticipated. The serum concentration of antifungal agents may rise when taking etravirine (Azole Derivatives, Systemic). With the use of voriconazole, this would be expected. Management: Keep an eye out for etravirine's enhanced side effects and toxicity. Ketoconazole, itraconazole, or posaconazole may require antifungal dose adjustment, although there are no precise dosing recommendations available. |
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Fedratinib |
Fedratinib's serum levels may rise when taken with CYP3A4 Inhibitors (Strong). Management: When feasible, take into account alternatives. Fedratinib dosage should be reduced if combined to 200 mg daily. Increase fedratinib dosage to 400 mg/day as tolerated when the inhibitor is withdrawn, starting at 300 mg/day for the first two weeks. |
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FentaNYL |
The serum levels of FentaNYL may rise when using CYP3A4 Inhibitors (Strong). Management: After starting this combination, keep a watchful eye on the patients for a few days and alter the fentanyl dosage as necessary. |
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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. |
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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. |
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May lower the serum level of antifungal agents (Azole Derivatives, Systemic). The serum concentration of fosphenytoin may rise in response to antifungal agents (systemic azole derivatives). In separate monographs, relevant Isavuconazonium concerns are covered. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. |
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Histamine H2 Receptor Antagonists |
Posaconazole's serum levels can drop. Management: Whenever possible, refrain from using oral suspension concurrently with H2-antagonists. If this combination is utilised, keep a watchful eye on the patients for any diminished antifungal effects. Posaconazole pills with delayed release might make interactions less likely. |
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Posaconazole may raise the level of Ibrutinib in the blood. Ibrutinib dose decreases are necessary when posaconazole is added. Ibrutinib dosage recommendations are based on the posaconazole dose and the ibrutinib indication. For details, see the entire monograph. |
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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. |
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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. |
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Ixabepilone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. |
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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. |
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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. |
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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. |
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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. |
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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. |
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Meperidine's serum levels may rise in response to strong CYP3A4 inhibitors. Management: If concurrent usage with potent CYP3A4 inhibitors is necessary, take into account lowering the dose of meperidine. When these medications are taken together, keep an eye out for any signs and symptoms of sedation and respiratory depression. |
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MethylPREDNISolone's levels in the serum may rise in response to CYP3A4 Inhibitors (Strong). Treatment: If a patient is using a potent CYP3A4 inhibitor, consider lowering the dose of methylprednisolone and keep an eye out for any increased steroid-related side effects. |
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The serum concentration of MiFEPRIStone may rise in response to CYP3A4 Inhibitors (Strong). Management: When paired with a potent CYP3A4 inhibitor, the adult dose of mifepristone for treating hyperglycemia in Cushing's syndrome should not exceed 600 mg/day. Regardless of dose or indication, keep an eye out for increased mifepristone toxicity. |
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Mirodenafil |
The serum concentration of Mirodenafil may rise in response to CYP3A4 Inhibitors (Strong). When used with potent CYP3A4 inhibitors, mirodenafil dosage may want to be reduced. When using this combination, keep an eye out for any increased toxicities or side effects from mirodenafil. |
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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. |
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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. |
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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. |
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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. |
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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. |
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Phenytoin |
The serum levels of phenytoin may rise when taking antifungal agents (systemic azole derivatives). In separate monographs, relevant Isavuconazonium concerns are covered. Phenytoin may lower the level of antifungal agents in the serum (Azole Derivatives, Systemic). Treatment: Since antifungal failure is likely, concurrent therapy with phenytoin and itraconazole, voriconazole, or ketoconazole is usually best avoided. Think about choosing an alternative antifungal treatment. |
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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. |
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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. |
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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. |
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Proton Pump Inhibitors |
May decrease the serum concentration of Posaconazole. |
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Reboxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. |
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Rifamycin Derivatives |
The serum concentration of Rifamycin Derivatives may be raised by antifungal agents (systemic azole derivatives). Rifabutin appears to be the only drug impacted. Rifamycin derivatives may lower the level of antifungal agents in the serum (Azole Derivatives, Systemic). Management: Whenever you can, stay away from these pairings. Isavuconazonium and voriconazole are regarded as contraindicated. |
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Ruxolitinib's serum levels may rise in response to CYP3A4 Inhibitors (Strong). Management: There are specific situations where this combination should be avoided. Monograph for more information. |
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It's possible that CYP3A4 Inhibitors (Strong) will raise SAXagliptin's serum levels. The U.S. product labelling for saxagliptin advises restricting the adult dose to 2.5 mg/day when used with a potent CYP3A4 inhibitor. Keep an eye out for elevated saxagliptin levels or effects. The product labelling in Canada does not include an advice of this nature. |
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Posaconazole may raise the level of Sildenafil in the blood. Management: When sildenafil is used to treat pulmonary arterial hypertension, concurrent posaconazole is not advised. For the first dose of sildenafil while treating erectile dysfunction, 25 mg of posaconazole is advised. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Solifenacin. Management: Limit solifenacin doses to 5 mg daily when combined with strong CYP3A4 inhibitors. |
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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). |
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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. |
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Tacrolimus (Systemic) |
Posaconazole may boost Tacrolimus' serum levels (Systemic). When commencing posaconazole, reduce tacrolimus dosage to roughly one-third of the initial dose. Blood levels of tacrolimus should be closely watched both during and after stopping posaconazole. |
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Posaconazole may raise the level of Tadalafil in the serum. |
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Posaconazole may elevate serum levels of Temsirolimus' active metabolite or metabolites. Management: Take into account posaconazole substitutes or temsirolimus dose decreases. All patients on posaconazole or any other systemic azole antifungal should have their sirolimus levels monitored. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
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Risk Factor X (Avoid combination) |
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Acalabrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. |
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The serum concentration of aprepitant may rise in response to CYP3A4 Inhibitors (Strong). |
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Astemizole |
The serum levels of Astemizole may rise in response to posaconazole. |
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Asunaprevir |
Asunaprevir's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong). |
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AtorvaSTATin |
AtorvaSTATin's serum levels may rise in response to posaconazole. |
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Avanafil |
Avanafil's serum levels may rise in response to posaconazole. |
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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. |
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Barnidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. |
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Blonanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. |
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Bosutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. |
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Budesonide (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). |
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Posaconazole may increase the serum concentration of Cisapride. |
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Cobimetinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. |
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Conivaptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. |
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Dabrafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. |
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Dapoxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. |
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Dihydroergotamine's serum levels may rise in response to posaconazole. |
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Posaconazole may raise the level of Dofetilide in the serum. |
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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. |
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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. |
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Posaconazole's serum levels can drop. |
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Eletriptan's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong). |
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Eplerenone's serum levels may rise in response to posaconazole. |
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Ergoloid Mesylates |
Ergoloid Mesylates' serum levels may rise in response to posaconazole. |
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Ergonovine's serum levels may rise in response to posaconazole. |
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Posaconazole may raise the level of ergotamine in the blood. |
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Everolimus |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. |
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Fluticasone (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. |
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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. |
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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. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. |
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Lercanidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. |
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Lomitapide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. |
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Lovastatin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. |
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Lumacaftor |
May decrease the serum concentration of Posaconazole. |
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Lurasidone |
The serum levels of lurasidone may rise in response to strong CYP3A4 inhibitors. |
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The serum concentration of Macitentan may rise in response to strong CYP3A4 inhibitors. |
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Posaconazole may increase Methadone's ability to prolong QTc. The serum concentration of methadone may rise in response to posaconazole. |
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Methylergonovine serum levels may rise in response to posaconazole. |
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Mizolastine |
Mizolastine's serum levels may rise in response to antifungal agents (systemic azole derivatives). |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. |
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Pimozide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. |
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QT-prolonging CYP3A4 Substrates |
Posaconazole may elevate the serum levels of CYP3A4 substrates that prolong QT. The risk of proarrhythmic effects and other comparable toxicities may increase as a result of such increases. |
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Posaconazole may raise the level of QuiNIDine in the blood. |
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Radotinib |
The presence of CYP3A4 Inhibitors (Strong) may raise the level of Radotinib in the serum. |
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Ranolazine's metabolism may be slowed down by systemic antifungal agents (azole derivatives). Considerations related to fluconazole and isavuconazonium are covered in different monographs. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. |
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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. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. |
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Antifungal (Systemic, Oral) Agents may lessen Saccharomyces boulardii's therapeutic impact. |
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Salmeterol's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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The serum levels of Silodosin may rise in response to CYP3A4 Inhibitors (Strong). |
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Simeprevir's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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Simvastatin's serum levels may rise in response to CYP3A4 Inhibitors (Strong). |
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Posaconazole may raise the level of Sirolimus in the blood. |
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Sonidegib's serum levels may rise in the presence of CYP3A4 Inhibitors (Strong). |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. |
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Terfenadine |
Posaconazole may increase the serum concentration of Terfenadine. |
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CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. |
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Udenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. |
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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. |
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VinCRIStine (Liposomal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). |
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Vinflunine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. |
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CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. |
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Monitoring parameters:
Hepatic function:
- Monitor liver function tests, including AST, ALT, alkaline phosphatase, and bilirubin, before starting posaconazole and periodically during treatment.
Renal function:
- Evaluate renal function, especially in patients receiving intravenous (IV) therapy, if the estimated glomerular filtration rate (eGFR) is less than 50 mL/minute/1.73 m².
Serum electrolytes:
- Check levels of calcium, magnesium, and potassium before initiating posaconazole therapy and monitor them during treatment.
Complete Blood Count (CBC):
- Regularly monitor CBC to assess any potential hematologic abnormalities.
Breakthrough fungal infections:
- Watch for any signs of breakthrough fungal infections, especially in patients with severe renal impairment taking delayed-release tablets or oral suspension.
Adequate oral intake:
- Ensure that patients are able to take posaconazole orally and maintain adequate oral intake.
Therapeutic Drug Monitoring Considerations:
- Invasive aspergillosis: The Infectious Diseases Society of America (IDSA) recommends monitoring serum trough concentrations in patients receiving posaconazole oral suspension for the treatment or prolonged prophylaxis of invasive aspergillosis. However, further studies are needed to determine if therapeutic drug monitoring is necessary or beneficial for delayed-release tablets or IV formulations of posaconazole.
- Limited evidence: Currently, there is limited evidence supporting therapeutic drug monitoring for posaconazole. However, due to the variability in bioavailability and potential drug interactions, it is advised to consider therapeutic drug monitoring, as individual responses to posaconazole can vary.
How to administer Posaconazole (Noxafil)?
Oral Administration:
- Suspension: Before use, shake the suspension well. Administer the dose using the provided dosing spoon. Take the suspension during or within 20 minutes after a full meal. If unable to eat a full meal, patients may take each dose with an oral liquid nutritional supplement or an acidic carbonated beverage (like ginger ale). If a patient cannot eat a full meal or tolerate a liquid supplement or beverage and cannot take the delayed-release tablet or injection, consider an alternative antifungal.
- Tablets (delayed release): Swallow the tablets whole, without dividing, crushing, dissolving, or chewing. Take the tablets with food.
- Monitor patients experiencing severe diarrhea or vomiting closely for signs of breakthrough fungal infections.
Intravenous (IV) Administration:
- Infusion: Administer the IV formulation over 90 minutes through a central venous line. Do not give it as an IV push or bolus. Use an in-line filter (0.22-micron PES or PVDF) during infusion. If necessary, the IV infusion may be given through a peripheral line over 30 minutes as a one-time infusion, but only if a central venous line will be used for subsequent doses or during the replacement or use of the central venous line for another infusion. Posaconazole may cause irritation. It is important to note that multiple peripheral infusions given through the same vein in clinical trials resulted in infusion-site reactions.
Note: These administration instructions are essential to follow to ensure proper delivery and effectiveness of posaconazole therapy. It is recommended to adhere to the specific administration guidelines provided by the healthcare provider or included in the product information.
Mechanism of action of Posaconazole (Noxafil):
- Posaconazole works by interfering with the activity of a fungal enzyme called lanosterol-14α-demethylase, which is involved in the synthesis of ergosterol.
- Ergosterol is a crucial component of the fungal cell membrane.
- By inhibiting lanosterol-14α-demethylase, posaconazole reduces the production of ergosterol, leading to the disruption of fungal cell membrane formation.
- This interference with fungal cytochrome P450 enzyme activity ultimately weakens the structure and integrity of the fungal cells, preventing their growth and replication.
Absorption:
- Oral suspension: The absorption of posaconazole from the oral suspension is unpredictable and variable. Optimal absorption occurs when taken with a high-fat meal in four divided doses. However, absorption may still be sufficient if taken with a nutritional supplement or acidic beverage like ginger ale.
- Tablet (delayed-release): The absorption of posaconazole from the delayed-release tablet is predictable. It is recommended to administer the tablet with food, but absorption is still sufficient even under fasting conditions.
Distribution:
- Volume of distribution: In oral form, posaconazole has a volume of distribution of 287 liters, while in injection form, it is approximately 261 liters.
- Protein binding: Posaconazole is highly bound to proteins, with more than 98% of the drug being bound to albumin.
Metabolism:
- Posaconazole is not significantly metabolized. Only 17% of the drug undergoes non-CYP-mediated metabolism, primarily through hepatic glucuronidation into metabolites.
Bioavailability:
- The bioavailability of posaconazole differs between the oral suspension and delayed-release tablets. The delayed-release tablets result in higher plasma exposure compared to the suspension.
- Suspension: The bioavailability of the suspension depends on the gastric pH environment, with decreased absorption in higher pH or increased motility conditions. Absorption is increased when taken in a high-fat environment.
- Delayed release tablets: The bioavailability of the tablets is influenced by the fed condition. Under fasted conditions, it is 54%, but it increases by 51% when taken with a high-fat meal.
Half-life elimination:
- Suspension: The elimination half-life of posaconazole from the oral suspension is approximately 35 hours, with a range of 20 to 66 hours.
- Tablets: The elimination half-life of posaconazole from the delayed-release tablets is between 26 to 31 hours.
- Injection: The elimination half-life of posaconazole from the injection is around 27 hours.
Time to peak plasma concentration:
- Suspension: The time to reach peak plasma concentration for posaconazole from the oral suspension is approximately 3 to 5 hours.
- Tablets: The time to reach peak plasma concentration for posaconazole from the delayed-release tablets is about 4 to 5 hours.
Excretion:
- Posaconazole is primarily excreted in the feces, with approximately 71% of the total dose being eliminated this way. Most of the excreted drug in the feces remains unchanged.
- A small portion (13%) of the drug is excreted in the urine, with less than 0.2% of the total dose being eliminated unchanged.
International Brand Names of Posaconazole:
- Noxafil
- Posanol
- Asperonazol
- Noxafil EC
- Posanol
- Spirafil
- Zolafungi
Posaconazole Brand Names in Pakistan:
No Brands Available in Pakistan.
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