Appendix 1: Grapefruit Interacting Drugs and Associated ...

1 Appendix to: Bailey DG, Dresser G, Arnold JMA. Grapefruit and medication interactions: forbidden fruit or avoidable consequences? CMAJ 2012; Copyright 2012 Canadian Medical Association or its licensors Appendix 1: Grapefruit Interacting Drugs and Associated Oral Bioavailability, Adverse Event(s), Risk Ranking and Potential Alternative Medications Interacting Drugs Innate Oral Bioavailability*Dose-Related Drug Adverse Event(s) Predicted Interaction Risk Rank ** Potential Alternative Medication(s)** Anti-Cancer Agents crizotinib intermediatetorsade de pointes, myelotoxicityhighcyclophosphamide highloss of efficacyintermediatedasatinib not knowntorsade de pointes, myelotoxicityhighimatiniberlotinib intermediatemyelotoxicityhigheverolimus low myelotoxicity, nephrotoxicityhighimatinib highmyelotoxicityintermediatelapatinib incompletetorsade de pointes, myelotoxicityhighnilotinib intermediate torsade de pointes, myelotoxicityhighimatinibpazopanib incompletetorsade de pointes.

2 Myelotoxicityhighsorafenibsorafenib intermediatemyelotoxicityintermediatesun itinib not knowntorsade de pointes, myelotoxicityhighsorafenibvandetanib not knowntorsade de pointes, myelotoxicityhighvenurafenib not knowntorsade de pointes, myelotoxicityhighAnti-Diabetic Agents repaglinide intermediatehypoglycemiaintermediateglyb uride, metformin, sitagliptin saxagliptin intermediate hypoglycemiaintermediateglyburide, metformin, sitagliptin Anti-Infective Agents albendazole low dizziness, headache, nausea intermediateartemether low enhanced anti-malarial efficacylowerythromycin intermediatetorsade de pointeshighclarithromycinetravirine not knownskin rashlowhalofantrine low torsade de pointesvery highdoxycyclinemaraviroc low postural hypotension , syncope very high enfuvirtide praziquantel low dizziness, headache, somnolence intermediateprimaquine intermediatemyelotoxicityhighdoxycycline quinine intermediate torsade de pointeshighdoxycyclineAppendix to: Bailey DG, Dresser G, Arnold JMA.

3 Grapefruit and medication interactions: forbidden fruit or avoidable consequences? CMAJ 2012; Copyright 2012 Canadian Medical Association or its licensors rilpivirine not knowntorsade de pointes high nevirapine saquinivir very lowenhanced HIV efficacylowamprenavir, indinivirAnti-Inflammatory Agents budesonide oral intermediatehyperglycemia, Cushingoid features intermediate colchicine not knownneutropenia, neuropathyintermediateprednisone, ibuprofen methylprednisolone -oral intermediatehyperglycemia, Cushingoid features intermediate prednisoneAnti-Lipemic Agents atorvastatin lowrhabdomyolysis highpravastatin,rosuvastatin, fluvastatin lovastatin very lowrhabdomyolysisvery highpravastatin,rosuvastatin, fluvastatin simvastatin very low rhabdomyolysisvery highpravastatin, rosuvastatin, fluvastatin Cardiovascular Agents amiodarone intermediatetorsade de pointeshighsotalolamlodipine highhypotension.

4 Peripheral edemalowapixaban intermediateGI bleedinghighwarfarincilostazol not knownGI bleeding highacetylsalicylic acidclopidogrel very lowloss of efficacyhighacetylsalicylic aciddronedarone low torsade de pointesvery highsotaloleplerenone intermediate hyperkalemia, serious arrhythmias high spironolactone ergotamine very lowgangrene, strokevery higha triptan class drugfelodipine lowhypotension, peripheral edemaintermediateamlodipinelosartan intermediateloss of efficacyintermediatemanidipine lowhypotension, peripheral edemaintermediateamlodipinenicardipine lowhypotension, peripheral edemaintermediateamlodipinenifedipine intermediatehypotension, peripheral edemaintermediateamlodipinenimodipine very lowhypotension, peripheral edemaintermediatenisoldipine very lowhypotension, peripheral edemaintermediateamlodipinenitrendipine lowhypotension, peripheral edemaintermediateamlodipinepropafenone lowbradycardia.

5 Conduction disorders intermediate quinidine high torsade de pointesintermediateAppendix to: Bailey DG, Dresser G, Arnold JMA. Grapefruit and medication interactions: forbidden fruit or avoidable consequences? CMAJ 2012; Copyright 2012 Canadian Medical Association or its licensors rivaroxaban highGI bleedingintermediatewarfarinsibutramine not knownhypertensionintermediate sildenafil intermediatehypotension intermediate tadalafil intermediatehypotensionintermediate ticagrelor intermediateGI or kidney bleeding high acetylsalicyclic acid vardenafil

6 Intermediatehypotensionintermediate verapamil intermediatecomplete heart blockhighdiltiazemCNS Agents aprepitant intermediate drowsiness, headache low alfentanil oral intermediaterespiratory depressionhighhydromorphone, morphine buspirone very lowdizziness, sedation high oxazepam, tamazepam carbamazepine highataxialowphenytoin,clonazepam dextromethorphan very lowhallucinations, somnolencehighdiazepam lowsedationintermediatealprazolam, oxazepam, tamazepam fentanyl oral intermediate respiratory depressionhighhydromorphone, morphine fluvoxamine not knownadverse change in mood intermediatecitralopram, paroxetine, escitalopram ketamine oral lowrespiratory depressionvery highhydromorphone, morphine lurasidone lowtorsade de pointes, orthostatic hypotension , syncope very highhaloperidol, risperidone olanzapine methadone highrespiratory depressionintermediatemidazolam oral intermediatesedationintermediatealprazol am.

7 Lorazepam oxycodone intermediaterespiratory depressionhighhydromorphone, morphine pimozide intermediatetorsade de pointeshighhaloperidol, risperidone, olanzapine quazepam intermediatesedationlowalprazolam, oxazepam temazepam quetiapine very lowdizziness, somnolence highhaloperidol, risperidone, olanzapine sertraline intermediatedizziness, somnolenceintermediatecitralopram, paroxetine, escitalopram triazolam intermediatesedationintermediatealprazol am, lorazepam ziprasidone intermediatetorsade de pointeshighhaloperidol, risperidone Appendix to: Bailey DG, Dresser G, Arnold JMA.

8 Grapefruit and medication interactions: forbidden fruit or avoidable consequences? CMAJ 2012; Copyright 2012 Canadian Medical Association or its licensors olanzapineEstrogens estradiol lowbreast cancer risk, thrombosisintermediateethinylestradiol intermediatebreast cancer risk, thrombosisintermediateGastrointestinal Agents cisapride intermediatetorsade de pointeshighmetoclopramidedomperidone lowtorsade de pointesvery highmetoclopramideImmunosuppressant Agents cyclosporine lownephrotoxicity higheverolimus low myelotoxicity, nephrotoxicityhighsirolimus lowmyelotoxicity.

9 Nephrotoxicityhightacrolimus lownephrotoxicityhighUrinary Tract Agents darifenacin lowurinary retention, constipation intermediatefesoterodine intermediateurinary retention, constipationintermediatesolifenacin hightorsade de pointesintermediatesilodosin intermediatepostural hypotension , dizzinessintermediatetamsulosin intermediatepostural hypotension , dizzinessintermediate * Innate oral drug bioavailability is the population average: very low (<10%), low (>10-30%), intermediate (>30 70%), high (>70%) ** Predicted Risk Rank is based initially upon the seriousness of the dose-related adverse drug effect and then adjusted dependent upon the innate oral bioavailability of the drug, which is used to determine the potential magnitude of increase in systemic drug concentration (see text).

10 There are four categories of risk ranking: very high, high, intermediate, low. It is recommended for older patients, particularly the elderly, that Drugs in the very high or high c