Tacrolimus : interactions médicamenteuses

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Avoid alcoholic beverages. (notice Tacrolimus, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. (notice Amiodarone, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

This risk which can be fatal should be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades de pointes, those with proarrhythmic conditions, and with other drugs that prolong the QT interval. (notice Azithromycine, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors. (notice Captopril, Mises en garde)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval. (notice Ciprofloxacine, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Immunosuppressant/neoplastic: everolimus Co-administration of everolimus and PREZISTA/ritonavir is not recommended. irinotecan Discontinue PREZISTA/ritonavir at least 1 week prior to starting irinotecan therapy. (notice Darunavir, Interactions médicamenteuses)

Use with Drugs that Prolong QT Interval and Antiarrhythmic Agents The use of dofetilide in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended. (notice Dofétilide, Mises en garde)

Concomitant use of COMPLERA with drugs with a known risk to prolong the QTc interval of the electrocardiogram may increase the risk of Torsade de Pointes. (notice Emtricitabine, rilpivirine et ténofovir, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole. (notice Fluconazole, Contre-indications)

Chicken pox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant corticosteroids. (notice Fludrocortisone, Mises en garde)

Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. (notice Flunisolide, Précautions)

Because of foscarnet's tendency to cause renal impairment, the use of FOSCAVIR should be avoided in combination with potentially nephrotoxic drugs such as aminoglycosides, amphotericin B, cyclosporine, acyclovir, methotrexate, tacrolimus and intravenous pentamidine (see above) unless the potential benefits outweigh the risks to the patient. (notice Foscarnet, Interactions médicamenteuses)

Avoid co-administration of CONTEPO with drugs known to prolong the QT interval. (notice Fosfomycine, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Therefore, PLAQUENIL is not recommended in patients taking other drugs that have the potential to prolong the QT interval. (notice Hydroxychloroquine, Mises en garde et précautions)

Avoid the use of FANAPT in combination with any other drugs that prolong the QT interval [see Warnings and Precautions (5.3) ] . (notice Ilopéridone, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Immunosuppressants Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after TOLSURA treatment. (notice Itraconazole, Interactions médicamenteuses)

Bradycardia may increase the risk of QT prolongation which may lead to severe ventricular arrhythmias, including torsade de pointes, especially in patients with risk factors such as use of QTc prolonging drugs [see Adverse Reactions ( 6.2 )] . (notice Ivabradine, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval ( 5.11 , 8.5 ) (notice Lévofloxacine, Mises en garde et précautions)

Avoid use in patients with congenital long QT syndrome, those with hypokalemia, and with other drugs that prolong the QT interval. (notice Lopinavir et ritonavir, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…as simvastatin, lovastatin, and CYP3A substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, due to an increased risk of adverse events. [See Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] Patients receiving systemic corticosteroids for lifesaving… (notice Mifépristone, Contre-indications)

Le millepertuis peut affaiblir ces médicaments en accélérant leur dégradation, ce qui peut se traduire par un rejet d'organe, des caillots ou une perte d'effet. (NCCIH, St. John's Wort)

Examples diazepam, alprazolam, alcohol Drugs that Prolong QTc Interval Clinical Impact The concomitant use of other drugs which prolong the QTc interval with REMERON/REMERONSolTab, increase the risk of QT prolongation and/or ventricular arrhythmias (e.g., Torsades de Pointes). (notice Mirtazapine, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…methylergonovine • HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use [see Table 2 , Drug Interactions (7.3) ] ) • Immunosuppressants: voclosporin • Microsomal triglyceride transfer protein inhibitor: lomitapide • Migraine medications: eletriptan, ubrogepant • Mineralocorticoid receptor antagonists:… (notice Nirmatrelvir et ritonavir, Contre-indications)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Avoid coadministration of oxaliplatin injection with medicinal products with a known potential to prolong the QT interval. (notice Oxaliplatine, Interactions médicamenteuses)

Avoid grapefruit or grapefruit juice. (notice Tacrolimus, Interactions médicamenteuses)

Avoid coadministration of VOTRIENT with drugs known to prolong the QT/QTc interval. (notice Pazopanib, Interactions médicamenteuses)

Drugs that Prolong the QT Interval : Avoid concomitant use. (notice Phénobarbital, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Because pimozide prolongs the QT interval of the electrocardiogram it is contraindicated in patients with congenital long QT syndrome, patients with a history of cardiac arrhythmias, patients taking other drugs which prolong the QT interval of the electrocardiogram or patients with known hypokalemia or hypomagnesemia (see also PRECAUTIONS - DRUG INTERACTIONS ). (notice Pimozide, Contre-indications)

The use of WAKIX should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval [see Drug Interactions ( 7.1 )]. (notice Pitolisant, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Nephrotoxicity and leukoencephalopathy (including deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine or tacrolimus concentrations. (notice Posaconazole, Mises en garde et précautions)

• Avoid use with other antiarrhythmic agents or drugs that prolong the QT interval. (notice Propafénone, Mises en garde et précautions)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Avoid the concomitant use of drugs known to prolong the QTc interval. (notice Sertraline, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Certain conditions may increase the risk for torsade de pointes or sudden death such as (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval [see Warnings and Precautions ( 5.8 ), Clinical Pharmacology (12.2) ]. (notice Tétrabénazine, Interactions médicamenteuses)

CONTRAINDICATIONS Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. (notice Thioridazine, Contre-indications)

Therefore, serum concentrations of the calcineurin inhibitor should be monitored during treatment with TYGACIL to avoid drug toxicity. (notice Tigécycline, Interactions médicamenteuses)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

…IN TRANSPLANT PATIENTS; AND INCREASED MORTALITY IN FEMALE LIVER TRANSPLANT PATIENTS • Increased risk for developing serious infections and malignancies with ASTAGRAF XL ® or other immunosuppressants that may lead to hospitalization or death. [see Warnings and Precautions ( 5.1 , 5.2 )] • Increased mortality in female liver transplant patients with ASTAGRAF XL. (notice Tacrolimus, Mise en garde encadrée)

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (notice Vepdégestrant, Mises en garde et précautions)

Therefore, ziprasidone should not be given with: • dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol or tacrolimus. (notice Ziprasidone, Contre-indications)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Concomitant use of agents associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers) may increase the risk for hyperkalemia [see Adverse Reactions ( 6.1 )] . (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Frequent PT/INR determinations are advisable until it has been definitely determined that the PT/INR has stabilized Immunosuppressants Clinical Impact: Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route… (notice Acide fénofibrique, Interactions médicamenteuses)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

However, this is of special importance in patients at risk of or having underlying renal dysfunction and patients taking concomitant nephrotoxic agents such as cyclosporine, tacrolimus, aminoglycosides, vancomycin and non-steroidal anti-inflammatory drugs [See Adverse Reactions (6.2) and Clinical Pharmacology (12.3) ]. (notice Adéfovir, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib [see Clinical Pharmacology (12.3) ]. (notice Afatinib, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Tacrolimus Administration of multiple doses of anidulafungin and a single-dose of tacrolimus to healthy subjects resulted in no significant alteration in the steady state pharmacokinetics of either drug. (notice Anidulafungine, Interactions médicamenteuses)

Other drugs, such as: Magnesium and aluminum hydroxide antacids Metoclopramide May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.7 , 5.10 , 5.11 )]. (notice Tacrolimus, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

MAO inhibitors, tricyclic antidepressants and drugs that prolong the QTc interval may potentiate effect on the cardiovascular system. (notice Arformotérol, Interactions médicamenteuses)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. (notice Bendamustine, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Other drugs, such as: Magnesium and aluminum hydroxide antacids Metoclopramide May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.7 , 5.10 , 5.11 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

Concomitant use of agents associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers) may increase the risk for hyperkalemia [see Adverse Reactions ( 6.1 )] . (notice Tacrolimus, Mises en garde et précautions)

The risk of combining buprenorphine with other QT-prolonging agents is not known. (notice Buprénorphine, Mises en garde et précautions)

The risk of combining buprenorphine with other QT-prolonging agents is not known. (notice Buprénorphine et naloxone, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Cannabidiol Drug Interactions When cannabidiol and ASTAGRAF XL are co-administered, closely monitor for an increase in tacrolimus blood levels and for adverse reactions suggestive of tacrolimus toxicity. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Caspofungin May decrease tacrolimus whole blood trough concentrations. (notice Tacrolimus, Interactions médicamenteuses)

Cannabidiol Drug Interactions When cannabidiol and ASTAGRAF XL are co-administered, closely monitor for an increase in tacrolimus blood levels and for adverse reactions suggestive of tacrolimus toxicity. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

QT Interval Prolongation and V entricular A rr h ythmia Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia. (notice Cinacalcet, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Avoid use of Citalopram Capsules in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure and patients taking other drugs that prolong the QTc interval. (notice Citalopram, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

…droperidol, pimozide), specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin), Class 1A antiarrhythmic medications (e.g., quinidine, procainamide) or Class III antiarrhythmics (e.g., amiodarone, sotalol), and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). (notice Clozapine, Mises en garde et précautions)

In another drug-drug interaction study in healthy volunteers, co-administration of LOKELMA 15 g decreased the systemic exposures of tacrolimus (Figure 2), likely due to LOKELMA’s action on elevating gastric pH. (notice Cyclosilicate de zirconium sodique, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections. (notice Dénosumab, Mises en garde et précautions)

Carefully monitor cardiac rhythm when administering SUPRANE to susceptible patients (e.g., patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval). (notice Desflurane, Mises en garde et précautions)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19 . (notice Dexlansoprazole, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

…cardiac disease, 3) treatment with Class I and Class III antiarrhythmics, 4) treatment with monoamine oxidase inhibitors (MAOI's), 5) concomitant treatment with other drug products known to prolong the QT interval (see PRECAUTIONS, Drug Interactions ), and 6) electrolyte imbalance, in particular hypokalemia and hypomagnesemia, or concomitant treatment with drugs… (notice Dropéridol, Mises en garde)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Strong CYP3A Inhibitors c : Protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone, letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations… (notice Tacrolimus, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as cyclosporine, everolimus, sirolimus and tacrolimus, caution and appropriate monitoring should be used [see Clinical Pharmacology (12.3) ] . (notice Élexacaftor, tézacaftor et ivacaftor, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. (notice Éribuline, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. (notice Ésoméprazole, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Immunosuppressants Clinical Impact: Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration of renal… (notice Fénofibrate, Interactions médicamenteuses)

…prolonged QT interval, 3) treatment with Class 1 and Class III antiarrhythmics, 4) treatment with monoamine oxidase inhibitors (MAOI's), 5) concomitant treatment with other drug products known to prolong the QT interval and 6) electrolyte imbalance, in particular hypokalemia and hypomagnesemia, or concomitant treatment with drugs (e.g., diuretics) that may cause electrolyte… (notice Fentanyl, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOI) [See Dosage and Administration ( 2.9 , 2.10 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.2 )] . (notice Fluoxétine, Interactions médicamenteuses)

…Antidepressants, QTc Prolonging Drugs Formoterol, as with other beta 2 -agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. (notice Formotérol, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. (notice Goséréline, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

This observation should be considered in making clinical decisions regarding patient monitoring when prescribing HYSINGLA ER in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QTc interval. (notice Hydrocodone, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Monitor QT interval when administering FORANE to susceptible patients (e.g., patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval). (notice Isoflurane, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

TYKERB may prolong the QT interval in some patients. (notice Lapatinib, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressants or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Lédipasvir et sofosbuvir, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. (notice Leuproréline, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Other Drugs that Prolong the QTc Interval Coadministration of other drugs known to alter cardiac conduction (e.g., anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H 1 -blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval. (notice Méfloquine, Interactions médicamenteuses)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Mild or Moderate CYP3A Inducers Methylprednisolone, prednisone May decrease tacrolimus whole blood trough concentrations. (notice Tacrolimus, Interactions médicamenteuses)

Other drugs, such as: Magnesium and aluminum hydroxide antacids Metoclopramide May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.7 , 5.10 , 5.11 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Drugs that Prolong the QT Interval QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. (notice Métronidazole, Interactions médicamenteuses)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Effect of Micafungin in Sodium Chloride Injection on Other Drugs CYP3A4 Substrates There was no effect of single or multiple doses of micafungin for injection on cyclosporine, tacrolimus, prednisolone, voriconazole and fluconazole pharmacokinetics. (notice Micafungine, Interactions médicamenteuses)

Strong CYP3A Inhibitors c : Protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone, letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations… (notice Tacrolimus, Interactions médicamenteuses)

…grapefruit juice is a strong CYP3A inhibitor; low dose or single strength grapefruit juice is a moderate CYP3A inhibitor. c Strong CYP3A inhibitor/inducer, based on reported effect on exposures to tacrolimus along with supporting in vitro CYP3A inhibitor/inducer data, or based on drug-drug interaction studies with midazolam (sensitive CYP3A probe substrate). (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Pharmacokinetic studies between moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. (notice Moxifloxacine, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Tacrolimus Clinical Impact : Concomitant use of esomeprazole magnesium and tacrolimus may increase exposure of tacrolimus Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets and tacrolimus, monitor tacrolimus whole blood concentrations. (notice Naproxène et ésoméprazole, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Calcium-channel blocking agents may increase tacrolimus blood concentrations and require dosage reduction of ASTAGRAF XL [see Drug Interactions ( 7.2 )] . (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and… (notice Tacrolimus, Interactions médicamenteuses)

Use olanzapine and fluoxetine capsules with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.20 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOIs) [See Dosage and Administration ( 2.4 , 2.5 ), Contraindications ( 4.1 ), and Warnings and Precautions ( 5.6 )] . (notice Olanzapine et fluoxétine, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

…or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions… (notice Tacrolimus, Interactions médicamenteuses)

…or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions… (notice Tacrolimus, Interactions médicamenteuses)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

…combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval. (notice Palipéridone, Mises en garde et précautions)

Drugs that Prolong QT: Use with caution in patients who are at significant risk of developing QTc prolongation. (notice Pasiréotide, Interactions médicamenteuses)

Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. (notice Pénicillamine, Mises en garde)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Mild or Moderate CYP3A Inducers Methylprednisolone, prednisone May decrease tacrolimus whole blood trough concentrations. (notice Tacrolimus, Interactions médicamenteuses)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

QT Interval Prolonging Drugs The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between Primaquine phosphate Tablets and other drugs that effect cardiac conduction is unknown. (notice Primaquine, Interactions médicamenteuses)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

…Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone). (notice Quétiapine, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19 . (notice Rabéprazole, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

In healthy subjects, 75 mg once daily and 300 mg once daily (3 times and 12 times the dose in EDURANT) have been shown to prolong the QTc interval of the electrocardiogram. (notice Rilpivirine, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

QT Interval Prolongation The overall analysis of ECG data in pediatric patients indicates that the concomitant use of Rocuronium Bromide Injection with general anesthetic agents can prolong the QTc interval [see Clinical Studies ( 14.3 )]. (notice Rocuronium, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

For oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy (e.g., cyclosporine, tacrolimus, levothyroxine), consider separation of the timing of the administration of the two drugs [see Clinical Pharmacology (12.3) ] . (notice Sévélamer, Interactions médicamenteuses)

Caution should be exercised when administering sevoflurane to susceptible patients (e.g., patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval). (notice Sévoflurane, Mises en garde)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Monitor electrolytes and electrocardiograms in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. (notice Sorafénib, Mises en garde et précautions)

…electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment in patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other products that lead to QT prolongation, and those with electrolyte disturbances (e.g., hypokalemia, hypocalcemia, or hypomagnesemia). (notice Tacrolimus, Mises en garde et précautions)

Drugs that Prolong the QT interval QT prolongation has been reported with metronidazole, a component of bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride, particularly when administered with drugs with the potential for prolonging the QT interval. (notice Sous-citrate de bismuth, métronidazole et tétracycline, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Drugs that Prolong QT Interval SUTENT is associated with QTc interval prolongation [see Warnings and Precautions (5.3) , Clinical Pharmacology (12.2) ] . (notice Sunitinib, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Prophylaxis of PJP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. (notice Temsirolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Cyclosporine, Tacrolimus: There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. (notice Tinidazole, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. (notice Triptoréline, Mises en garde et précautions)

…like other beta 2 -agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. (notice Uméclidinium et vilantérol, Interactions médicamenteuses)

Other drugs associated with myelosuppression or nephrotoxicity (e.g., adriamycin, dapsone, doxorubicin, flucytosine, hydroxyurea, pentamidine, tacrolimus, trimethoprim/ sulfamethoxazole, vinblastine, vincristine, and zidovudine) Unknown Because of potential for higher toxicity, coadministration with valganciclovir hydrochloride should be considered only if the… (notice Valganciclovir, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, Mises en garde et précautions)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

Reduce ASTAGRAF XL dose (for voriconazole and posaconazole, give one-third of the original dose) and adjust dose based on tacrolimus whole blood trough concentrations [see Dosage and Administration ( 2.3 , 2.4 ) and Clinical Pharmacology ( 12.3 )]. (notice Tacrolimus, Interactions médicamenteuses)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (notice Tacrolimus, Interactions médicamenteuses)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Atorvastatine, Mises en garde et précautions)

Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant. (notice Axitinib, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. (notice Ézétimibe et simvastatine, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum CK, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. (notice Fluvastatine, Mises en garde et précautions)

IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Lovastatine, Mises en garde)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Pitavastatine, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Pravastatine, Mises en garde et précautions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (notice Propylthiouracile, Mises en garde)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (notice Rosuvastatine, Mises en garde et précautions)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. (notice Simvastatine, Mises en garde et précautions)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (notice Thiamazole, Mises en garde)