Systemic Anticancer Therapy Drug Interactions Table Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 1 of 28 This guide is intended to cover the most common interactions involving Systemic Anticancer therapies, e.g. cytotoxic agents, monoclonal antibodies and targeted therapies. Whilst every effort has been made to ensure it is a comprehensive resource, there may be some interactions which have been unintentionally omitted. Please interpret the information contained in this guide in addition to clinical information and performance status. Copyright Northumbria Healthcare NHS Trust & North of England Cancer Network Version 4.1 October 2012 (Date of Review October 2014) Any comments on this document to [email protected] DRUG INTERACTION WITH INFORMATION REFERENCE Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 2 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Cisplatin Increased risk of pulmonary toxicity when used in combination Clozapine Increased risk of agranulocytosis 1 Possibility of reduced absorption of digoxin tablets-switch to Digoxin liquid Bleomycin Patients receiving bleomycin pre-operatively are at greater risk of developing pulmonary toxicity when oxygen is administered Oxygen at surgery. A reduction in inspired oxygen concentration during 2 operation and post-operatively is recommended Oral anti diabetic drugs Monitor blood glucose levels, hyperglycaemia in is common 3 Clozapine Increased risk of agranulocytosis 1 Bortezomib Potent CYP3A4 inhibitors and inducers (particularly ketoconazole, Closely monitor as may affect plasma concentration of 1, 3 rifampicin, carbamazepine, bortezomib phenytoin and St Johns Wart) Clozapine Increased risk of agranulocytosis 1 Cyclophosphamide serum levels may be increased (& active Cyclophosphamide metabolite decreased) if given within 24 hours of busulfan 4 Itraconazole and Metronidazole Increase in busulfan toxicity 1,3 Busulfan Ketobemidone Increase in busulfan plasma concentration Paracetamol May decrease intravenous busulfan plasma levels 4 Phenytoin Increases busulfan clearance Tioguanine Increased risk of hepatotoxicity 1 Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 3 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Allopurinol Possible decreased efficacy of capecitabine 5,6 Aluminium and aluminium Small increase in capecitabine toxicity 5 containing antacids Cimetidine Increased plasma concentration 1 Clozapine Increased risk of agranulocytosis 1 Coumarins Enhanced anticoagulant effect, monitor INR regularly Erlotinib Could increase plasma concentration of erlotinib Increased toxicity of capecitabine, maximum tolerated dose is Folinic acid 1,5 reduced. Decreased rate of capecitabine absorption if administered with Capecitabine Food food. Manufacturers recommend administration within 30 minutes of a meal. Maximum tolerated dose of capecitabine is decreased by Interferon Alpha interferon alpha 6 Metronidazole Increased toxicity 1 Phenytoin May lead to increased phenytoin levels 5 Potentially fatal combination – leads to increased Sorivudine and analogues fluoropyrimidine activity Increased photosensitivity risk when topical fluorouracil and 1, 5 Temoporfin temoporfin used concomitantly Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 4 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Allopurinol Potential for increased risk of toxicity when used in combination Amiodarone Concomitant use may lead to early onset pulmonary toxicity 6 Fluconazole and itraconazole inhibit the metabolism of Azole antifungals cyclophosphamide, leading to increased toxicity Cyclophosphamide serum levels may be increased (and active Busulfan 5 metabolite decreased) if given within 24 hours of busulfan Increased renal toxicity when used in combination or in patients Cisplatin 6 who have had prior treatment with cisplatin Cyclophosphamide Clozapine Increased risk of agranulocytosis 1 Digoxin Reduces absorption of digoxin tablets 1 Potentiated by cyclophosphamide Oral antidiabetic drugs -monitor blood glucose levels 7 Increased risk of toxicity when pentostatin is given with high Pentostatin dose cyclophosphamide Rifampicin Increased metabolism of cyclophosphamide 6 Suxamethonium Enhances effect of suxamethonium 1 Aldesleukin Avoid concomitant use 8 Dacarbazine Clozapine Increased risk of agranulocytosis 1 Cytochrome P450 (CYP1A1, Darcarbazine is metabolised by cytochrome P450, therefore 8 CYP1A2, and CYP2E1) levels may be altered if co-administered with other substrates Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 5 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Clozapine Increased risk of agranulocytosis 1 Metabolism of docetaxel clearance altered, may lead to CYP3A inducers and inhibitors 9 increased toxicity or reduced efficacy of docetaxel. Docetaxel Lapatinib Increased risk of neutropenia 9 Ritonavir Plasma concentration of docetaxel increased 1 Sorafenib Increases the plasma concentration of docetaxel 1 Amphotericin B Marked increase in nephrotoxicity Reduced absorption of anticonvulsants when administered in Anticonvulsants combination with doxorubicin 10 Anthracyclines and Cardiotoxic Monitor cardiac function as increased risk of cardiotoxicity medication Calcium Channel Blockers Plasma concentration of doxorubicin is increased 1 (verapramil) Doxorubicin Ciclosporin Increased risk of neurotoxicity 1 Clozapine Increased risk of agranulocytosis 1 Cytarabine Potential for severe infections and necrosis of intestine CYP3A4 inhibitors Reduction in plasma concentration Cytochrome P450 inducers and May affect doxorubicin metabolism, leading to increased 10 inhibitors toxicity or decreased efficacy Possibility of reduced absorption of oral bioavailability of Digoxin digoxin May increase concentration of epirubicin metabolites when Epirubicin 11 docetaxel administered immediately after epirubicin Hepatotoxic medication Increased risk of hepatoxicity when used in combination 10 (e.g. 6 – mercaptopurine) Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 6 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Manufacturer advises to leave at least 24 hours between Paclitaxel infusing both drugs as elimination of doxorubicin may be 10 reduced if given within 24 hours of paclitaxel. Doxorubicin (continued) Ritonavir Elevated serum doxorubicin concentration 10 Uric acid lowering agents Doxorubin therapy may lead to an increase in serum uric acid 1 Doxorubicin patients should not be actively vaccinated and also Vaccines 1, 10 avoid contact with recently polio vaccinated patients Cardiotoxic medication Monitor cardiac function as increased risk of cardiotoxicity 11 Ciclosporin Plasma concentration of epirubicin increased by ciclosporin Increases plasma concentration of epirubicin, not explained by 1 Cimetidine CYP activity Clozapine Increased risk of agranulocytosis Dexverapamil Possible increased bone marrow suppression May increase concentration of epirubicin metabolites when Docetaxel Epirubicin docetaxel administered immediately after epirubicin Interferon alpha 2b May reduce total clearance of epirubicin Hepatotoxic medication May affect epirubicin efficacy and toxicity 11, 1 Live vaccines Live vaccines should be avoided Increased risk of toxicity, manufacturers advise at least 24 Paclitaxel hours between infusions if used in combination Quinine Can accelerate distribution of epirubicin into the tissues Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 7 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Clozapine Increased risk of agranulocytosis Enzyme inducers Increased eribulin plasma concentration Eribulin Inhibitors of hepatic transport May reduce elimination of eribulin and result in up to three fold proteins increase in plasma concentration 12 Eribulin may inhibit CYP3A4, resulting in increased plasma Substrates of CYP3A4 concentration of the substrate. Avoid concomitant use if substrate has narrow therapeutic range. Plasma concentration of erlotinib potentially reduced by Antacids antacids. Give antacids at least 4 hours before or 2 hours after Antivirals (bocepravir) Avoid co-administration 1 Clozapine Increased risk of agranulocytosis Enhanced anticoagulant effect, monitor INR regularly as Coumarins increased risk of bleeding CYP1A2 inhibitors/inducers May alter erlotinib levels 13 CYP3A4 inhibitors/inducers May alter erlotinib levels Erlotinib Avoid concomitant use with cimetidine. Give erlotinib at least 2 H2 receptor antagonists 1 hours before or 10 hours after ranitidine. May reduce plasma concentration-smoking cessation advice Nicotine 13 should be given. NSAIDS Increased risk of bleeding 1 P-glycoprotein inhibitors May alter erlotinib levels 13 May alter erlotinib levels- manufacturers recommend avoid PPIs 1 concomitant use Statins May increase risk of rhabdomyolysis 13 Ref: SACT Interactions Table 4.1 Prepared By J. Allen Checked By S.Williamson/ M.Nagra September 2012 Page 8 of 28 DRUG INTERACTION WITH INFORMATION REFERENCE Atovaquone Increases plasma concentration of etoposide 1 Etoposide clearance may be increased by phenytoin and Antiepileptics phenobarbital 1, 6 Ciclosporin Increased risk of etoposide toxicity with high dose ciclosporin Etoposide 1 Clozapine