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; caution should be exercised with concomitant administration of AZD1755 (MK-1775) and agents that are sensitive substrates of cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), 2C9 and 2C19, or substrates of this enzyme with narrow therapeutic ranges, as well as agents that are inhibitors or substrates of permeability glycoprotein (P-gp)
CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
Patients must be able to discontinue CYP2C9 substrates with a narrow therapeutic index (e.g. warfarin, phenytoin), if randomized to TGR-1202; patients must discontinue such agents at least 1 week or 5 half-lives prior to beginning protocol therapy (whichever is longer)
Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow therapeutic indices: 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
Sensitive or narrow therapeutic range substrates of CYP2D6
Exposure to sensitive or narrow therapeutic range substrates of the drug metabolising enzymes CYP2C8, CYP2C9, CYP2C19 or the drug transporters Pgp, BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 within the appropriate wash-out period before the first dose of study treatment.
Chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index. A washout period of 7 days is required prior to venetoclax dosing if a prohibited medication is discontinued.
An oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of dosing in the study
Require continued treatment with a medication that is a sensitive CYP2C9 substrate with a narrow therapeutic index.
Medications that have a narrow therapeutic window and are predominantly metabolized through CYP2C8, CYP2C9, CYP2C19, or CYP3A4;
known P gp substrates with a narrow therapeutic index
Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib.
Participants receiving any medications, substances, or foods (i.e., grapefruit juice) listed below are ineligible:\r\n* Prescription or non-prescription drugs or other products known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued prior to study start and withheld throughout the study until 2 weeks after the last dose of study drug; sensitive substrates of CYP2C8, CYP2C9, CYP2C19, or substrates of these enzymes with narrow therapeutic range\r\n* Inhibitors or substrates of P-glycoprotein (P-gp)
Patients who are currently receiving drugs that are strong or moderate inhibitors and/or inducers of CYP3A4, sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range are not eligible; the use of aprepitant or fosaprepitant as an antiemetic is prohibited due to early drug interaction data demonstrating increased exposure to AZD1775; the use of hydroxymethylglutary (HMG) coenzyme-A (Co-A) inhibitors such as atorvastatin is prohibited
Patient has had prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug; co-administration of aprepitant or fosaprepitant during this study is prohibited; the use of sensitive substrates of CYP3A4, such as atorvastatin, simvastatin and lovastatin, is also prohibited in this study; transporter studies (in vitro) have shown that AZD1775 is an inhibitor of breast cancer resistance protein (BCRP); herbal preparations are not allowed throughout the study; these herbal medications include but are not limited to: St. John's wort, kava, ephedra (ma hung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng; patients should stop using these herbal medications 7 days prior to first dose of study treatment
Any chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or inhibitors or sensitive substrates of CYP3A or CYP2D6 with a narrow therapeutic window Abiraterone-Specific Exclusion Criteria:
Patients may not be receiving any other investigational agent for any purpose concurrently; patients may not require ongoing treatment with (a) gastric pH modifying medications including proton pump inhibitors or H2 blockers (patients may switch to antacids), (b) medications which are known to be sensitive substrates or substrates with a narrow therapeutic index for the P-gp and BCRP transporters and/or (c) medications known to cause corrected QT (QTc) prolongation with risk of Torsades
Rx or non-Rx drugs or other products known to be sensitive BCRP or OAT1 substrates or to be potent inhibitors/inducers of CYP1A2, which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of AZD4635.
Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
Is chronically taking a sensitive CYP3A substrate or a CYP3A substrate with a narrow therapeutic index and cannot be switched to an alternative agent at least 7 days prior to study initiation that in the opinion of investigator/treating physicians precludes utilization of idelalisib
Drugs which are substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a narrow therapeutic window; or which are strong inhibitors of drug transporter MDR1.
Concomitant receipt of the following sensitive CYP substrate medications that have a narrow therapeutic range (unless the participant can be transferred to other medications at least 5 half-lives prior to the start of study treatment): paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)
Concurrent therapy with strong inhibitors or inducers of CYP3A4 or CYP2C8 or with sensitive substrates of CYP3A4, CYP2C9 or CYP2C19
Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
Patients receiving medications that are known to be substrates of CYP2C8 (including paclitaxel), CYP2C9, or CYP2C19 or to be oral substrates of CYP3A with narrow therapeutic window; subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of merestinib
Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.
Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
Trametinib may be an inhibitor of CYP2C8 in vivo; caution should be exercised when dosing trametinib concurrently with medications with narrow therapeutic windows that are substrates of CYP2C8
An oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of dosing in the study
Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index
Concurrent administration of strong inducers and inhibitors of CYP3A enzyme or CYP3A substrates with narrow therapeutic window
Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
Concomitant use of strong CYP3A4, CYP1A2, or CYP2C9 substrates
Subject has had prescription or non-prescription drugs or other products known to be sensitive cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior (alternatively 5 half lives if T1/2 is known) prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug\r\n* NOTE: co-administration of aprepitant or fosaprepitant during this study is prohibited\r\n* Note: individual drugs exerting CYP interactions may be continued on a case by case basis if felt essential for patient management, after discussions and discretion of the treating physician\r\n* The preferred azole anti-fungal medication is fluconazole (alternatively posaconazole) which can be given during treatment with AZD1775 at the treating physician’s discretion, however with dose reductions of AZD1775 by 25-75% (i.e. from AZD1775 200mg to 150 or 100mg)
known to be substrates of CYP3A4/5 and P-gp with a narrow therapeutic index
Unable or unwilling to discontinue use of any sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic window
Patient has had prescription or non-prescription drugs or other products (i.e., grapefruit juice) known to be sensitive to cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 2 weeks before day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug
Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index; if an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
All CYP2C8 inhibitors, inducers, and substrates should be discontinued >= 7 days prior to registration; systemic treatment with CYP2C8 inhibitors (anastrozole, montelukast, quercetin, trimethoprim, gemfibrozil, rosiglitazone, pioglitazone), inducers (carbamazepine, phenytoin, rifabutin, rifampin), or substrates (amiodarone, repaglinide, rosiglitazone, sorafenib, torsemide) should be discontinued >= 7 days prior to registration
Patient has had prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug; co-administration of aprepitant or fosaprepitant during this study is prohibited; the use of sensitive substrates of CYP3A4, such as atorvastatin, simvastatin and lovastatin, is also prohibited in this study
Patient has had a prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to day -3 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant or fosaprepitant during this study is prohibited.
Current use of strong CYP3A inhibitors such as ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, and clarithromycin are prohibited; NOTE: moderate inhibitors of CYP3A4 should be used with caution; navitoclax is a moderate inhibitor of CYP2C8 and a strong inhibitor of CYP2C9; caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins and repaglinide; CYP2C9 substrates include celecoxib, phenytoin and warfarin; when possible, investigators should switch to alternative medications or monitor the patients closely
Drugs known to be CYP3A4 substrates with narrow therapeutic windows (such as alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, sirolimus, or terfanide) or CYP2C8 substrates are not allowed; patients must be switched to alternative drugs at least 14 days prior to receiving the first dose of AMG 232; those patients who cannot switch to alternative drugs will be excluded from the study
Strong CYP2C8 inhibitors or CYP2C8 substrates
OATP1B1/3 substrates Received the following within 14 days prior to the initiation of study treatment: * Strong CYP2C8 inducers
Strong CYP2C8 inhibitors or CYP2C8 substrates
OATP1B1/3 substrates
Use of any known CYP3A4 substrates with narrow therapeutic window (such as alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, sirolimus, or terfanide) within the 14 days prior to receiving the first dose of AMG 232 is not permitted; other medications (such as fentanyl and oxycodone) may be allowed per investigator’s assessment/evaluation
Drugs that potently inhibit cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should be prohibited or used with caution; drugs which are strong inducers of CYP3A and may result in lower exposures of GSK2141795 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\r\n* Caution should be exercised when dosing trametinib concurrently with medications with narrow therapeutic windows that are substrates of CYP2C8; drugs that potently inhibit or induce CYP3A4 should be administered with caution\r\n* Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; 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\r\n* The following medications (including but not limited to) are prohibited during the study:\r\n** PROHIBITED-highly sensitive and/or low therapeutic index\r\n*** Cisapride\r\n*** Pimozide\r\n*** Astemizole\r\n*** Rosuvastatin, sulfasalazine\r\n** PROHIBITED-strong inducers/inhibitors of CYP3A4\r\n*** Clarithromycin, telithromycin, rifamycin class agents (e.g., rifampin, rifabutin, rifapentine), troleandomycin\r\n*** Itraconazole, ketoconazole\r\n*** Nefazodone\r\n*** Atazanavir, delavirdine, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, nevirapine\r\n*** Carbamazepine, phenobarbital, phenytoin\r\n* The following medications (including but not limited to) that may alter the concentrations of trametinib or GSK2141795 or have their elimination altered by trametinib or GSK2141795 should be administered WITH CAUTION:\r\n** USE WITH CAUTION-Drugs potentially affecting trametinib or GSK2141795 concentrations\r\n*** Quinidine, diltiazem, verapamil\r\n*** Fluvoxamine, fluoxetine, paroxetine, nefazodone\r\n*** Aprepitant, cimetidine\r\n*** Fluconazole, terbinafine, voriconazole\r\n*** Ciprofloxacin, erythromycin, isoniazid\r\n*** Mibefradil, diltiazem, verapamil\r\n*** Aprepitant, oxandrolone, tizanidine, gemfibrozil\r\n** USE WITH CAUTION-Drugs that may inhibit permeability (P)-glycoprotein (gp) and breast cancer resistance protein (BCRP)\r\n*** Valspodar\r\n*** Atorvastatin\r\n*** Carvedilol\r\n*** Methadone\t\r\n*** Meperidine\t\r\n*** Omeprazole\r\n** USE WITH CAUTION-Drugs that may have their concentrations altered by trametinib or GSK2141795\r\n*** Repaglinide, rosiglitazone, pioglitazone\r\n*** Alfentanil, fentanyl\t\r\n*** Quinidine \r\n*** Cilostazol\r\n*** Astemizole\r\n*** Diergotamine, ergotamine, eletriptan\r\n*** Pimozide\r\n*** Buspirone\r\n*** Felodipine\r\n*** Sildenafil, tadalafil, vardenafil\r\n*** Cerivastatin, lovastatin, simvastatin, atorvastatin\r\n*** Alprazolam, diazepam, midazolam, triazolam\r\n*** Cyclosporine, sirolimus, tacrolimus\r\n*** Cisapride\r\n*** Cyclosporine, torsemide, chloroquine, zopiclone\r\n*** Eplerenone\t\r\n*** Chloroquine, zopiclone\r\n** Use of repaglinide, rosiglitazone and/or pioglitazone is permitted only after consultation with the Cancer Therapy Evaluation Program (CTEP) Medical Monitor
Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are sensitive CYP2B6 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates.
Concomitant use of agents with narrow therapeutic windows that are metabolized by CYP3A4, cytochrome P450 2D6 (CYP2D6), or cytochrome P450 2C8 (CYP2C8) is not recommended
Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication
Participants taking medications that are known potent CYP3A4 inducers/inhibitors or substrates with narrow therapeutic indices or St. John's Wort.
Sensitive CYP3A4/5 substrates or CYP3A4/5 substrates with narrow therapeutic index (NTI)
Sensitive CYP2D6 substrates or CYP2D6 substrates with NTI
Selected dual substrates of CYP3A4/5 and CYP2C8
Selected dual substrates of CYP3A4/5 and CYP2D6
Selected dual substrates of OATP and CYP450
Selected dual substrates of CYP3A4/5 and P-gp
NTI P-gp substrates
Prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.
Use of any medications that induce, inhibit, or are substrates of CYP450 3A4
Use of any known CYP2C8 substrates with a narrow therapeutic window is not allowed during the study and patients must come off 14 days prior to receiving the first dose of AMG 232
Use of any known CYP3A4 substrates with narrow therapeutic window (such as alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, sirolimus, or terfanide) within the 14 days prior to receiving the first dose of AMG 232; other medications (such as fentanyl and oxycodone) may be allowed per investigator’s assessment/evaluation
Patients requiring medications metabolized through CYP3A4/5 and have a narrow therapeutic index or medications that are CYP3A4 substrates that cause QT prolongation
Patients requiring medications that are sensitive CYP2D6 substrates areCYP2D6 substrates with a narrow therapeutic index or are anti-arrhythmic drugs/drugs with QT-prolongation risks
Patients requiring medications with narrow therapeutic index CYP3A4 substrates
Patients who require the following treatments moderate to strong CYP3A4 inhibitors; any substrates of CYP3A4/5 with a narrow therapeutic index
If a potential study patient is taking any of the medications in the categories described below, the investigator will assess and document the use of medications known or suspected to fall in the following medication categories:\r\n* Moderate/weak CYP3A inducers such as efavirenz and oxcarbazepine\r\n* CYP2C8 substrates such as thiazolidinediones (glitazones) and select statins (because of expected inhibition of the metabolism of CYP2C8 substrates) by venetoclax\r\n* CYP2C9 substrates such as tolbutamide (because of expected inhibition of the metabolism of CYP2C9 substrates by venetoclax; it is recommended to exclude CYP2C9 substrates with a narrow therapeutic index such as phenytoin
Exposure to sensitive or narrow therapeutic range substrates of the drug metabolizing enzymes CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 within the appropriate wash-out period (a minimum of 5 x reported elimination half-life) before the first dose of study treatment
Medi4736+AZD5069 Cohort only: received any potent and moderate cytochrome CYP3A4 inhibitors, potent and moderate CYP3A4 inducers, P-gp substrates, BCRP substrates, sensitive CYP2B6 substrates, warfarin and coumarin derivatives, or herbal supplements within 14 days of the first dose of study treatment
Patients who are currently receiving treatment (that cannot be discontinued at least 1 week prior to the initiation of the study) with agents that are known to be any of the following: strong inducers or inhibitors of CYP3A4/5; sensitive substrates of CYP3A; substrates of CYP3A4/5 or CYP2C9 with a narrow therapeutic index.
Receiving medications that are moderate or strong inhibitors or inducers of CYP3A4 or that are sensitive substrate or substrates with a narrow therapeutic index of CYP3A4, CYP2D6, or CYP2C9 (see Appendix D)
Use of cytochrome P450 isoenzyme 3A4 (CYP3A4)/ CYP2C19 substrates
Substrates of CYP2D6 with a narrow therapeutic index (eg, thioridazine);
Subjects taking the following sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications within ?5 half-lives prior to dosing: paclitaxel (CYP2C8) warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline and tizanidine (CYP1A2).
CYP3A4 substrates with narrow therapeutic index
Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in subjects receiving pazopanib and others should be avoided or administered with extreme caution and require principal investigator (PI) approval\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; 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 prohibited\r\n* Medications which have narrow therapeutic windows and are substrates of CYP3A4, CYP2D6, or CYP2C8 should be avoided and, if necessary, administered with caution\r\n* Pazopanib, 800 mg once daily, has no effect on CYP2C9, CYP1A2, or CYP2C19 in vivo but does in vitro; therefore, therapeutic doses of warfarin, a substrate of CYP2C9, and omeprazole, a substrate of CYP2C19 are permitted; caffeine, a substrate of CYP1A2, is also permitted
All subjects must agree to stop the use of any known CYP3A4 substrates with narrow therapeutic window (such as alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, sirolimus, or terfanide; within the 14 days prior to receiving the first dose of AMG 232 and during protocol AMG 232 treatment (weeks 1-5); other medications (such as fentanyl and oxycodone) may be allowed per investigator’s assessment/evaluation
All subjects must agree to stop the use of any known CYP2C8 substrates with a narrow therapeutic window within the 14 days prior to receiving the first dose of AMG 232 and during protocol AMG 232 treatment (weeks 1-5)
Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5 or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there was an emergent or life-threatening medical condition that required it.
CYP3A4 or CYP2C19 or P glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrates having a narrow therapeutic index;
Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication
Substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19)\r\n* Preliminary results of a clinical drug-drug interaction study, examining the effect of ganetespib on the pharmacokinetics of the CYP2C19-sensitive probe omeprazole, show a modest (20%) increase in omeprazole exposure when coadministered with ganetespib; in vitro data implies expectation of greater interaction with CYP2C19 substrates than with CYP3A4 substrates; caution is advised when sensitive narrow therapeutic range CYP3A4 or CYP2C19 substrates are concomitantly administered
Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment
Subject has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates
Receiving treatment with medications that are known CYP3A, CYP1A2, CYP2C8, CYP2C9 or CYP2C19 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study.
Known poor metabolizers of CYP2C9 substrates
Subjects taking the following sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications prior to enrolling: paclitaxel (CYP2C8), warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline and tizanidine (CYP1A2)
Narrow therapeutic index substrates of CYP2C8, CYP2C9, CYP2C19 and CYP2D6
Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil);
Patients may not be on drugs known to be moderate or potent inhibitors/inducers of CYP3A4, sensitive substrates of CYP3A4, or substrates of CYP3A4 with narrow therapeutic windows
Participants who must receive CYP2C8 inhibitors, substrates and inducers, strong CYP3A4 inducers, or OATP1B1/3 substrates while on study. These must be discontinued 7 days (inhibitors and substrates) or 14 days (inducers) prior to start of study medication
Use with caution:\r\n* CYP2C19 non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study\r\n* CYP3A4/5 sensitive substrates and any non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study\r\n* CYP2D6 inducers, moderate/strong inhibitors or sensitive substrates are permitted if no acceptable alternatives are available; however, caution should be used; other non-sensitive substrates or weak inhibitors of CYP2D6 are allowed on study
Permeability-glycoprotein (P-gp) substrates with a narrow therapeutic index
Patients who are currently receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with WNT974:\r\n* Strong inhibitors or inducers of cytochrome P450, subfamily IIIA, polypeptide 4/5 (CYP3A4/5)\r\n* CYP3A4/5 substrates with narrow therapeutic index\r\n* Known to prolong the QT interval and are also CYP3A4/5 substrates
Use of drugs metabolized by CYP2D6; these are called CYP2D6 substrates
On scheduled CYP3A4 substrates with narrow safety range at the time of study enrollment (alfentanil, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus)
Currently receiving medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. Strong inducers, inhibitors and substrates must be discontinued at least 7 days prior to the first administration of study drug.
Inability to discontinue drugs that are strong cytochrome P450 3A4 (CYP3A4) or P450 3A5 (CYP3A5), cytochrome P450 2C19 (CYP2C19), and cytochrome P450 2C9 (CYP 2C9) inhibitors and/or inducers; and substrates of CYP 3A4/5 or CYP1A2 that are sensitive or have a narrow therapeutic window at least three weeks prior to study registration
Use of any drugs or substances known to be CYP3A4 substrates with narrow therapeutic range within 1 week prior to Day 1, or planned to be used during the overall study period.
Need to use drugs that have a narrow therapeutic index and are substrates for CYP2B6, CYP2C8, CYP2C9, CYP2C19, OATP1B1, OATP1B3, and OCT1 (organic cation transporter 1), ie warfarin, digoxin, phenytoin, paclitaxel, S-mephenytoin
Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices such as astemizole, terfenadine, cisapride, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, (alfentanil and fentanyl, including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) should be used with caution
Concurrent use of drugs that are CYP2C9 substrates with narrow therapeutic indices, such as warfarin, phenytoin or a sensitive substrate such as celecoxib should be used with caution
Concurrent use of drugs that are sensitive CYP2B6 substrates, such as bupropion, efavirenz should be used with caution
Caution should be exercised when inhibitors or substrates of P-glycoprotein (P-gP), substrates of cytochrome P450 family 1 subfamily A member 2 (CYP1A2) with a narrow therapeutic range, sensitive substrates of cytochrome P450 family 2 subfamily C member 19 (CYP2C19) or CYP2C19 substrates with a narrow therapeutic range are administered with AZD1775
Subject has had prescription or non-prescription drugs or other products known to be sensitive cytochrome P450 family 3 subfamily A member 4 (CYP3A4) substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors / inducers of CYP3A4 which cannot be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug; co-administration of aprepitant or fosaprepitant during this study is prohibited
Patients who are taking medications that may alter the metabolism of zolpidem; this includes strong CYP3A4 inhibitors or inducers or CYP3A4 substrates with a narrow therapeutic index
Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, and pimozide.
Patients who are taking medications that may alter the metabolism of enzalutamide; this includes the following: strong or moderate CYP2C8 inhibitors or inducers; strong CYP3A4 inhibitors or inducers; or CYP2C9, 2C19 or 3A4 substrates with a narrow therapeutic index
CYP3A substrates with narrow therapeutic window (including, but not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).