Participants are to discontinue the use of the following classes of inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); patients who are on these drugs are eligible if a washout period of a minimum of 7 days occurs before start of olaparib and temozolomide:\r\n* Azole antifungals\r\n* Macrolide antibiotics\r\n* Protease inhibitors
Patients taking substrates, inhibitors, or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
Concurrent therapy with strong inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) due to concerning possible drug-drug interactions
Patients with concomitant use of drugs, herbal supplements and/or ingestion of foods known to modulate cytochrome P450 family 3 subfamily A member 4 (CYP3A4) enzyme activity as specified in the drug specific appendix
Caution should be exercised when dosing navitoclax concurrently with cytochrome P450, family 2, subfamily C, peptide 8 (CYP2C8) and cytochrome P450, family 2, subfamily C, peptide 9 (CYP2C9) substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; cytochrome P450, family 3, subfamily A (CYP3A) inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration
Treatment with strong cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19), cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) inhibitors and/or inducers must be discontinued at least 1 week before administration of the first dose of study drug
Patients receiving any medications that are known to be strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), or sensitive substrates of CYP3A4, cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) or permeability glycoprotein (P-gp) with a narrow therapeutic index
Patients currently receiving (or unable to stop use at least 1 week prior to receiving the 1st dose of AZD9291) medications or herbal supplements known to be potent inhibitors of cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; patients are eligible if they stop use of these compounds at least 1 week prior to receiving any treatment on this protocol
Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2), CYP1A3, cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), CYP2C19, cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), UDP glycosyltransferase 1 family, polypeptide A1 (UGT1A1), P-glycoprotein, or breakpoint cluster region pseudogene (BCRP) are ineligible; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Concomitant therapy with any drugs shown to have major interactions with nortriptyline (i.e. known inhibitors of cytochrome P450 family 2 subfamily D member 6 [CYP2D6]) and use during the 30-day period prior to study start
Drugs that affect the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) systems are allowed but should be used with caution depending on specific kinase inhibitor used
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation:\r\n* Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes\r\n* Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)\r\n* Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, and/or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)\r\n* Therapeutic doses of warfarin sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban)\r\n* Unstable or increasing doses of corticosteroids; if patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms (non-central nervous system [CNS]), dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment\r\n* Enzyme-inducing anticonvulsive agents\r\n* Herbal supplements
Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) subfamily IIIA, polypeptide 4 (3A4), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) or cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) within 1 week preceding the first dose of study drug
Concomitant use of medications that are known cytochrome p450 family 3 subfamily A member 4 (CYP3A4) substrates
Nonclinical studies indicate that DS-3032b is metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/5; drugs that are strong inhibitors or inducers of these enzymes may alter the PK of DS-3032b and should therefore be avoided; St. John’s wort (hypericin) will not be permitted for 30 days before and during participation in the study; foods or beverages containing grapefruit should not be taken within 48 hours before initial dose of study drug and throughout the duration of the study
Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin) are ineligible; patients on strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors will also be excluded
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation:\r\n* Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes\r\n* Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/cytochrome P450, family 3, subfamily A, polypeptide 4 (5)\r\n* Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and/or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) \r\n* Therapeutic doses of warfarin sodium (Coumadin) or any other Coumadin-derived anti-coagulant\r\n* Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban)\r\n* Unstable or increasing doses of corticosteroids; if patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms (non-central nervous system [CNS]), dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment\r\n* Enzyme-inducing anticonvulsive agents\r\n* Herbal supplements
Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors where the interaction is thought too great to proceed with romidepsin
Any concomitant potent inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
Are taking strong or moderate cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inducers, or CYP3A4, cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) and cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) substrates with a narrow therapeutic index; patients may switch to an alternative any time prior to day 1 of trial drug administration
Concomitant use of strong inhibitors (e.g., ketoconazole, nefazodone, clarithromycin, gemfibrozil) or strong inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St John’s wort) of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8)
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of the study participation: \r\n* Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes \r\n* Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4/cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A4/5)\r\n* Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and/or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) \r\n* Therapeutic doses of warfarin sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban)\r\n* Unstable or increasing doses of corticosteroids\r\n* Enzyme-inducing anticonvulsive agents \r\n* Herbal supplements
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation\r\n* Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes \r\n* Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) \r\n* Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and/or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) \r\n* Therapeutic doses of warfarin sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban)\r\n* Unstable or increasing doses of corticosteroids; if patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms (non-central nervous system [CNS]), dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment\r\n* Enzyme-inducing anti-convulsive agents\r\n* Herbal supplements
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation:\r\n* Medication with a known risk of prolonging the QT interval or inducing torsades de pointes \r\n* Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/5 \r\n* Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and/or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) \r\n* Therapeutic doses (defined as doses need to achieve target INR > 1.5) of warfarin sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban)\r\n* Unstable or increasing doses of corticosteroids\r\n* Enzyme-inducing anticonvulsive agents\r\n* Herbal supplements
Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong cytochrome P450 family 3, subfamily C, polypeptide 8 (CYP2C8) inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates
Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/cytochrome P450, family 3, subfamily A, polypeptide 5 (5) or drugs metabolized by cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6) or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225
Caution should be exercised when dosing navitoclax concurrently with cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin and warfarin; when possible, investigators should switch to alternative medications or monitor the patients closely (particularly in the case of medications that have a narrow therapeutic window such as warfarin; use of warfarin is specifically prohibited while on study); cytochrome P450, family 3, subfamily A (CYP3A) inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; patient instructions and information of possible drug interactions will be given to all patients upon enrollment in this study
The following medications are prohibited during the study: \r\n* Substrates of cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), and cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) with a narrow therapeutic index, including paclitaxel, phenytoin, warfarin, omeprazole \r\n* Substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) with a narrow therapeutic index, including alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus\r\n* Strong CYP2C8 inhibitors, including gemfibrozil\r\n* Strong CYP3A4/5 inhibitors, including clarithromycin, itraconazole, ketoconazole
Strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 3A4) inhibitors (e.g., clarithromycin, human immunodeficiency virus [HIV] protease inhibitors, and itraconazole), given potential interactions with atorvastatin (atorvastatin calcium)
Concomitant use of drugs that are cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P, family 1, subfamily A, polypeptide 2 (CYP1A2), or cytochrome P, family 2, subfamily D, polypeptide 6 (CYP2D6) substrates
Drugs that affect the cytochrome P450 family 3 subfamily A polypeptide 4 (CYP3A4) system (inducers/inhibitors/substrates) are allowed but should be used with caution depending on specific kinase inhibitor used; dietary supplements will be discouraged; however, their use may be allowed on a case by case basis per the discretion of the investigator after consultation with an oncology pharmacist
Patients on drugs that are strong cytochrome P450, family 3, subfamily A, polypeptide 4 (P450 CYP3A4) modifiers; these drugs should be stopped 5 half-lives prior to starting investigational agents with temsirolimus; the strong inducing or inhibiting agents should not restart until 1 week after the end of the study treatment; NOTE: we will allow replacement of steroids (with either prednisone or hydrocortisone) in patients with adrenalectomy
Use of St. John’s wort, orrifampin (rifampicin), or other strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers; dexamethasone is okay as long as the dose is 16 mg /day or less\r\n* Note: patients who are on the above referenced medications may be considered eligible with a washout period of 14 days; contact the coordinating center to discuss patients with the above aforementioned agents before patient registration
Treatment with drugs that are substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), and cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) except for the ones that are explicitly permitted; prohibited medications include but are not necessarily limited to alfuzosin, amiodarone, astemizole, bepridil, “Chinese” (herbal) medicines, cisapride, cyclosporine, cyclophosphamide, desipramine, erythromycin, etoposide, fentanyl, flecainide, flutamide, grapefruit and grapefruit juice, halofantrine, ifosfamide, imipramine, lovastatin, mexiletine, modafinil, oxycodone, pimozide, propafenone, quetiapine, quinidine, simvastatin, tacrolimus, tamoxifen, terfenadine, thioridazine, vinblastine and vincristine; exception: those patients who are in the translational sub-study will receive a low dose of fentanyl (a substrate of CYP3A4) during the surgical procedure (100-200 mcg) for pain, along with ultra-short acting remifentanil (the latter has 8-10 min half-life)
Patients who are receiving drugs that significantly interact with the cytochrome P450 (CYP450) enzyme(s) are ineligible; however, if they are switched to other medications with a 2-week washout window, they will be eligible; patients are also excluded if they have been exposed within 7 days of planned first study treatment day to medications that are predominantly cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), cytochrome P450, family 2, subfamily C, polypeptide 9 (2C9) or cytochrome P450, family 2, subfamily C, polypeptide 19 (2C19) substrates, strong inhibitors or inducers, and sensitive substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) with narrow therapeutic range
Chronic concomitant treatment with strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors is not allowed; patients must discontinue the drug >= 14 days prior to registration
Drugs that strongly inhibit or potentiate cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4):\r\n* During Phase I: patients who have received these drugs within 14 days or within 5 half-lives of the drug (whichever is longer) prior to study initiation will be excluded\r\n* During Phase II: these drugs should be avoided if possible
Less than 1 week since prior treatment (most recent dose) with a potent cytochrome P450 family 3, subtype A, polypeptide 4 (3A4) (CYP3A4) inhibitor
Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) are ineligible (e.g. gemfibrozil, rifampin, trimethoprim, pioglitazone)
In vitro data indicate that GSK2141795 is a cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrate; drugs that potently inhibit CYP3A4 could lead to increased GSK2141795 exposure in subjects, and should either be prohibited or used with caution; drugs which are strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) and may result in lower exposures of GSK2141795 should also be prohibited; GSK2141795 also appears to be a moderate in vitro inhibitor of cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) (50% inhibitory concentration [IC50] 3 mcM) and CYP3A4 (IC50 11 mcM); drugs that are substrates of CYP3A4 or CYP2C8 with a narrow therapeutic index may be prohibited; drugs that are sensitive substrates of CYP3A4 or CYP2C8 should be used with caution
Patients chronically receiving medications known to be metabolized by cytochrome P 450, family 3, subfamily A, polypeptide 4 (CYP3A4) and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
The eligibility of patients taking medications that are potent modulators of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), subfamily 2, polypeptide 8 (2C8) will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications
Evaluation of the patient’s medications within 10 days prior to registration with attempt to change any medication that affects cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in patients receiving pazopanib and others should be avoided or administered with extreme caution\r\n* Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole may increase pazopanib concentrations and are prohibited; although, in exceptional circumstances, they may be administered in conjunction with lowering the dose of pazopanib by 50% of what would otherwise be administered; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib\r\n* Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib concentrations, are strictly prohibited\r\n* Medications that have narrow therapeutic windows and are substrates of CYP3A4, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) should be avoided and, if necessary, administered with caution
Prohibited medications: PKC412 and its two major metabolites may have a potential of drug-drug interactions with P-gp substrates and cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors, and inducers; an increased anticoagulant effect has been noted in patients treated with warfarin and midostaurin
As PF-02341066 is an inhibitor of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
Potent cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with T-DM1
Patients taking substrates, inhibitors and inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible
Patients that have been treated with strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors, CYP2C8 inducers, within 2 weeks of starting the trial treatment.
Current or anticipated need for treatment with drugs that are known substrates of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6)
Patients currently taking the following medications:\r\n* Cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors (e.g. Gemfibrozil)\r\n* CYP2C8 inducers (e.g. rifampin)\r\n* Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (itraconazole)\r\n* CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)
Finasteroid (propecia), efavirenz, red clover, ketoconazole and other drugs that are cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
Treatment with strong cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19), cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), and cytochrome P450 family 2 subfamily C member 9 (CYP2C9) inhibitors and/or inducers must be discontinued at least 1 week before administration of the first dose of study drug
Able to stop all cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (voriconazole or posaconazole) at least 7 days before admission
Concurrent use of agents that strongly inhibit or induce cytochrome P450 family 3, subfamily A (CYP3A) unless use is approved by the medical monitor
Concomitant use of medications that may alter pharmacokinetics of crizotinib or enzalutamide; would exclude the use of strong cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors, strong or moderate CYP3A inducers, CYP2C8, cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) and cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) substrates with narrow therapeutic indices
Concomitant use of narrow therapeutic index drugs that are metabolized by cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) (i.e. alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9) (phenytoin, warfarin), and cytochrome P450 family 2, subfamily C, polypeptide 19 (CYP2C19) (S-mephenytoin); (Note: patients on stable doses of anti-coagulation with warfarin and fentanyl will be eligible, as long as they are monitored closely with additional international normalized ratio [INR] monitoring)
Mifepristone inhibits cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) and induces CYP3A4; addition of mifepristone to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug concentration of drugs with significant CYP3A4 metabolism; medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's wort may decrease plasma mifepristone levels; strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma mifepristone concentrations; mifepristone may increase the plasma drug concentration of concomitant medications with metabolism mediated by cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)/cytochrome P450, family 2, subfamily C, polypeptide 8 (2C8)
Currently receiving treatment with agents that are metabolized solely through cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates; caution should be used in patients taking other CYP2C8- or CYP3A4/5-interacting agents
Potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with trastuzumab emtansine
Inability to withhold agents that may interact with hepatic cytochrome P450 enzymes (cytochrome P450 family 3, subfamily A, polypeptide 4 [CYP3A4]), or glutathione S-transferases involved in bortezomib and/or busulfan metabolism during day -5 through day +7; it is acceptable to use alternative non-interacting medications during this period, and then resume prior medications; importantly, no acetaminophen starting at HSCT admission, during conditioning chemotherapy and up to and including the stem cell infusion
Current systemic treatment with a potent cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitor such as ketoconazole or ritonavir
Drugs that are highly dependent on cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) for metabolism and have a narrow therapeutic index are allowed but must be used with caution
Medications with potent inducer or inhibitor of cytochrome P450 family 3, subfamily A, polypeptide 4 (P450 3A4) should be avoided within 5 half-lives of temsirolimus
Medications and/or diet are prohibited if they affect oral absorption of PF-00299804 or if primarily metabolized by cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6); patients must have been off treatment with these drugs for 2 weeks prior to enrollment; patients who otherwise are eligible can be enrolled only if drug substitution is performed with acceptable clinical outcome prior to enrollment
Patients with a seizure disorder may be enrolled if well controlled on anticonvulsants at a dose that has been stable for at least 14 days; however, drugs that induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, and phenobarbital) should be avoided
Drugs that potently inhibit cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should either be prohibited or used with caution; drugs which are strong inducers of cytochrome P450 family 3, subfamily A (CYP3A) should also be prohibited; drugs that are substrates of CYP3A4 or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) with a narrow therapeutic index may be prohibited; drugs that are sensitive substrates of CYP3A4 or CYP2C8 should be used with caution; it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians’ Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Drugs that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), p-glycoprotein (Pgp) or ATP-binding cassette, sub-family G, member 2 (Bcrp) transporter; the list may be modified based on emerging data; consider therapeutic substitutions for these medications; patients must be off treatment for at least 1 week prior to enrollment
Ongoing treatment with sensitive cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment
The participant requires chronic concomitant treatment with the following strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers OTHER than antiretroviral agents: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, primidone, modafinil, and other enzyme inducing anti-convulsant drugs (EIACD), and St. John’s Wort; use of efavirenz or etravirine is permitted for participants considered for the CYP3A4-inducer based antiretroviral therapy (ART) regimen arm (Stratum B) of the trial\r\n* Although study participants will be eligible regardless of smoking history, smokers should be strongly advised to stop smoking while on erlotinib; smoking induces cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) enzymes and alters erlotinib exposure by 64%
Concomitant use of drugs that strongly inhibit cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)
Patients must discontinue any medication that causes strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) induction 2 weeks prior to treatment initiation; patients who are not able to discontinue these drugs are considered ineligible
Patients may not receive strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors, CYP2C8 inducers, or cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers; in addition, patients should not receive drugs that are metabolized by CYP3A4 or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)
Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation:\r\n* Medication with a known risk of prolonging the QT interval or inducing torsades de pointes\r\n* Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A poly peptide 4/5 (CYP3A4/5)\r\n* Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, and/or cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9)\r\n* Therapeutic doses of warfarin sodium (Coumadin) or any other coumarin-derived anti-coagulant; anti-coagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban)\r\n* Unstable or increasing doses of corticosteroids\r\n* Enzyme-inducing anti-convulsive agents\r\n* Herbal supplements
Patients on any moderate or strong cytochrome P450 family 2, subfamily C, polypeptide 9 (CYP2C9) inducer (e.g., carbamazepine, rifampin) or inhibitor (e.g., amiodarone, fluconazole) are ineligible; CYP2C9 poor metabolizers will not be excluded
Patients on narrow-therapeutic drugs that are substrates for cytochrome P450 family 1, subfamily A, polypeptide 2 (CYP1A2), CYP2C9, cytochrome P450 family 2, subfamily C, polypeptide 19 (CYP2C19), and cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, phenytoin, pimozide, quinidine, sirolimus, tacrolimus, theophylline, tizanidine, warfarin)
Use of potent cytochrome P450 family 3, subfamily A, polypeptide 4 (3A4) (CYP3A4) inhibitor within one week of pacritinib initiation
Need for medications that strongly induce or inhibit cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) activity
Received potent cytochrome P450, family 3, subfamily A (CYP3A) inhibitors (e.g., ketoconazole) or inducers; or substrates of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) with narrow therapeutic indexes within 7 days prior to the first dose of study drug
It should be noted that TAK-700 (orteronel) is a weak inhibitor of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2), cytochrome P450, family 2, subfamily C, polypeptide 9 (2C9), and cytochrome P450, family 2, subfamily C, polypeptide 19 (2C19); caution should be employed when used with medications that are strong/moderate inhibitors, significant inducers or sensitive substrates with narrow therapeutic indices
Use of rifampin (strong cytochrome P450 family 2, subfamily C, polypeptide 8 [CYP2C8] inducer) within 14 days of study day 1
Patients cannot be taking any cytochrome P450, cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) pathway inhibiting or inducing agents (except proton pump inhibitors which are allowed) including cimetidine, antidepressants, antibiotics and all others
Patients who are currently receiving drugs that are strong or moderate inhibitors and/or inducers of cytochrome P450 family 3 subfamily A polypeptide 4 (CYP3A4) or sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range are not eligible; the use of aprepitant as an antiemetic is prohibited due to early drug interaction data demonstrating increased exposure to AZD1775; caution should be exercised with concomitant administration of AZD1775 and agents that are sensitive substrates of cytochrome P450 family 2 subfamily C polypeptide 8 (CYP2C8), family 2 subfamily C polypeptide 9 (2C9) and family 2 subfamily C polypeptide 19 (2C19), or substrates of this enzyme with narrow therapeutic ranges, as well as agents that are inhibitors or substrates of P-glycoprotein (P-gp)
Patients taking non-topical medication known to be a strong inhibitor of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); however patients who either discontinue their treatment or switch to another medication at least three days prior to randomization are eligible
Concomitant use of known cytochrome P450 (family 3, subfamily A, polypeptide 4, 5, 7 [3A4,5,7]) inducers such as carbamazepine, phenytoin, or oxcarbazepine
Use of select cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) inhibitor medications
Subjects being treated concurrently with any prohibited medications, including investigational medication, rifampin, St. John’s wort, and potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (excluding ketoconazole) unless continuation of such medications are determined by the investigator to be in the best interest of the patient
Patients who are on strong inhibitors of cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8), strong or moderate inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CY3A4) and CYP2C8 should discontinue these medications 2 weeks prior to the start of treatment
Patients taking any potent inhibitor of cytochrome P450 family 3, subfamily A, polypeptide 4 (3A4) (e.g., ketoconozole, itraconozole, erythromycin, etc)
Taking medications known to affect drug metabolism via the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), CYP, family 2, subfamily C, polypeptide 9 (CYP2C9), or CYP, family 2, subfamily D, polypeptide 6 (CYP2D6) pathways
Participants are to discontinue the use of the following classes of inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); patients who are on these drugs are eligible if a washout period of a minimum of 7 days occurs before start of olaparib and temozolomide\r\n* Azole antifungals\r\n* Macrolide antibiotics\r\n* Protease inhibitors
Patients taking substrates, inhibitors, or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible