Pharmacology drug interaction hand book f

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Pharmacology drug interaction hand book f

  1. 1. TOXIC DRUG INTERACTIONS AJITHBABU.T.K. 1
  2. 2. Interactions Two or more drugs given at the same time may exert their effectsindependently or may interact. The interaction may be potentiation or antagonismof one drug by another, or occasionally some other effect.Pharmacodynamic interactions These are interactions between drugs which have similar or antagonisticpharmacological effects or side effects. They may be due to competition atreceptor sites, or occur between drugs acting on the same physiological system.They are usually predictable from a knowledge of the pharmacology of theinteracting drugs; in general, those demonstrated with one drug are likely to occurwith related drugs. They occur to a greater or lesser extent in most patients whoreceive the interacting drugs.Pharmacokinetic interactions These occur when one drug alters the absorption, distribution, metabolism,or excretion of another, thus increasing or reducing the amount of drug availableto produce its pharmacological effects. They are not easily predicted and many ofthem affect only a small proportion of patients taking the combination of drugs.Pharmacokinetic interactions occurring with one drug cannot be assumed to occurwith related drugs unless their pharmacokinetic properties are known to besimilar.Relative importance of interactions Many drug interactions are harmless and many of those which arepotentially harmful only occur in a small proportion of patients; moreover, theseverity of an interaction varies from one patient to another. Drugs with a smalltherapeutic ratio (e.g. phenytoin) and those which require careful control ofdosage (e.g. anticoagulants, antihypertensives, and antidiabetics) are most ofteninvolved. Patients at increased risk from drug interactions include the elderly andthose with impaired renal or liver function.1.ALLOPURINOLAntivirals: allopurinol increases plasma concentration of didanosine (risk oftoxicity)—avoid concomitant use.Cytotoxics: allopurinol enhances effects and increases toxicity of azathioprineand mercaptopurine (reduce dose of azathioprine and mercaptopurine to onequarter of usual dose); avoidance of allopurinol advised by manufacturer ofcapecitabine. 2
  3. 3. 2.ALPHA BLOCKERSAntidepressants: enhanced hypotensive effect when alpha-blockers given withMAOIs; manufacturer of indoramin advises avoid concomitant use with MAOIs.Antivirals: plasma concentration of alfuzosin possibly increased by ritonavir—avoid concomitant use.Sildenafil: enhanced hypotensive effect when alphablockers given with sildenafil(avoid alpha-blockers for 4 hours after sildenafil).Sympathomimetics: avoid concomitant use of tolazoline with adrenaline(epinephrine) or dopamine.Tadalafil: enhanced hypotensive effect when alphablockers given with tadalafil—avoid concomitant use.Memantine: increased risk of CNS toxicity when amantadine given withmemantine (manufacturer of memantine advises avoid concomitant use); effectsof dopaminergics possibly enhanced by memantine.3.AMIODARONEAnti-arrhythmics: increased myocardial depression when anti-arrhythmics givenwith other antiarrhythmics; increased risk of ventricular arrhythmias whenamiodarone given with disopyramide—avoid concomitant use; amiodaroneincreases plasma concentration of flecainide (halve dose of flecainide)..Antibacterialserythromycin—avoid concomitant use; increased risk of ventricular arrhythmiaswhen amiodarone given with levofloxacin or moxifloxacin—avoid concomitant use;increased risk of ventricular arrhythmias when amiodarone given withsulfamethoxazole and trimethoprim (as co-trimoxazole) — avoid concomitant useof co-trimoxazole.Antidepressants: increased risk of ventricular arrhythmias when amiodaronegiven with tricyclics— avoid concomitant use arrhythmias when amiodarone givenwith pentamidine isetionate—avoid concomitant use.Antimalarials: avoidance of amiodarone advised by manufacturer of artemether/lumefantrine (risk of ventricular arrhythmias); increased risk of ventriculararrhythmias when amiodarone given with chloroquine and hydroxychloroquine,mefloquine or quinine—avoid concomitant use.Antipsychotics: increased risk of ventricular arrhythmias when anti-arrhythmicsthat prolong the QT interval given with antipsychotics that prolong the QT interval;increased risk of ventricular arrhythmias when amiodarone given with benperidol—manufacturer of benperidol advises avoid concomitant use; increased risk ofventricular arrhythmias when amiodarone given with amisulpride, haloperidol,phenothiazines, pimozide, sertindole or zuclopenthixol—avoid concomitant use;increased risk of ventricular arrhythmias when amiodarone given with sulpiride.Antivirals: plasma concentration of amiodarone possibly increased by atazanavir;plasma concentration of amiodarone possibly increased by fosamprenavir(increased risk of ventricular arrhythmias—avoid concomitant use); plasmaconcentration of amiodarone possibly increased by indinavir—avoid concomitant 3
  4. 4. use; increased risk of ventricular arrhythmias when amiodarone given withnelfinavir—avoid concomitant use; plasma concentration of amiodarone increasedby ritonavir (increased risk of ventricular arrhythmias—avoid concomitant use).Beta-blockers: increased risk of bradycardia, AV block and myocardial depressionwhen amiodarone given with beta-blockers; increased myocardial depression whenanti-arrhythmics given with beta-blockers; increased risk of ventriculararrhythmias when amiodarone given with sotalol—avoid concomitant use.Pentamidine Isetionate: increased risk of ventricular arrhythmias whenamiodarone given with pentamidine isetionate — avoid concomitant use.Corticosteroids: increased risk of hypokalaemia whenamphotericin given withcorticosteroids—avoidconcomitant use unless corticosteroids needed to controlreactions.4.ANAESTHETICS GENERALCytotoxics: nitrous oxide increases antifolate effect of methotrexate—avoidconcomitant use.Memantine: increased risk of CNS toxicity when ketamine given with memantine(manufacturer of memantine advises avoid concomitant use).5.ANAKINRAInfliximab: avoid concomitant use of anakinra with infliximab.Antidepressants: avoidance of fluvoxamine advised by manufacturer ofreboxetine; possible increased serotonergic effects when SSRIs given withduloxetine; fluvoxamine inhibits metabolism of duloxetine—avoid concomitant use;citalopram, escitalopram, fluvoxamine or paroxetine should not be started until 2weeks after stopping MAOIs, also MAOIs should not be started until at least 1week after stopping citalopram, escitalopram, fluvoxamine or paroxetine; CNSeffects of SSRIs increased by MAOIs (risk of serious toxicity); sertraline should notbe started until 2 weeks after stopping MAOIs, also MAOIs should not be starteduntil at least 2 weeks after stopping sertraline; fluoxetine should not be starteduntil 2 weeks after stopping MAOIs, also MAOIs should not be started until at least5 weeks after stopping fluoxetine; increased risk of CNS toxicity whenescitalopram given with moclobemide, preferably avoid concomitant use; afterstopping citalopram, fluvoxamine or paroxetine do not start moclobemide for atleast 1 week; after stopping fluoxetine do not start moclobemide for 5 weeks;after stopping sertraline do not start moclobemide for 2 weeks; increasedserotonergic effects when SSRIs given with St John’s wort—avoid concomitantuse; SSRIs increase plasma concentration of some tricyclics; agitation and nauseamay occur when SSRIs given with tryptophan.Anxiolytics and Hypnotics: fluvoxamine increases plasma concentration of somebenzodiazepines; fluvoxamine increases plasma concentration of melatonin—avoidconcomitant use; sedative effects possibly increased when sertraline given withzolpidem.6.ANTIDIPRESSANTS TRICYCLIC 4
  5. 5. Anti-arrhythmics: increased risk of ventricular arrhythmias when tricyclics givenwith amiodarone— avoid concomitant use; increased risk of ventriculararrhythmias when tricyclics given with disopyramide or flecainide; increased risk ofarrhythmias when tricyclics given with propafenone.Antimalarials: avoidance of antidepressants advised by manufacturer ofartemether/lumefantrine.Alcohol: increased sedation when tricyclic related antidepressants given withalcohol.Alpha -adrenoceptor Stimulants: avoidance of tricyclic- related antidepressantsadvised by manufacturer of apraclonidine and brimonidine.7.ANTI DIABETICSBosentan: increased risk of hepatotoxicity when glibenclamide given withbosentan—avoid concomitant use.Lipid-regulating Drugs: hypoglycaemic effect of acarbose possibly enhanced bycolestyramine; hypoglycaemic effect of nateglinide possibly enhanced bygemfibrozil; increased risk of severe hypoglycaemia when repaglinide given withgemfibrozil—avoid concomitant use; plasma concentration of rosiglitazoneincreased by gemfibrozil (consider reducing dose of rosiglitazone); plasmaconcentration of glibenclamide possibly increased by fluvastatin; may be improvedglucose tolerance and an additive effect when insulin or sulphonylureas given withfibrates.8.ANTI FUNGALS IMIDAZOLEAnti-arrhythmics: increased risk of ventricular arrhythmias when ketoconazolegiven with .disopyramide—avoid concomitant use.Antibacterials: metabolism of ketoconazole accelerated by rifampicin (reducedplasma concentration), also plasma concentration of rifampicin may be reduced byketoconazole; plasma concentration of ketoconazole possibly reduced by isoniazid;avoidance of concomitant ketoconazole in severe renal and hepatic impairmentadvised by manufacturer of telithromycin.Anticoagulants: ketoconazole enhances anticoagulant effect of .coumarins;miconazole enhances anticoagulant effect of .coumarins (miconazole oral gel andpossibly vaginal formulations absorbed); ketoconazole increases plasmaconcentration of rivaroxaban—avoid concomitant use.Antidiabetics: miconazole enhances hypoglycaemic effect of .gliclazide andglipizide—avoid concomitant use; miconazole increases plasma concentration ofsulphonylureas.Antihistamines: manufacturer of loratadine advises ketoconazole possiblyincreases plasma concentration of loratadine; imidazoles possibly inhibitmetabolism of .mizolastine (avoid concomitant use); ketoconazole inhibitsmetabolism of .mizolastine— avoid concomitant use.Antimalarials: avoidance of imidazoles advised by manufacturer of artemether/lumefantrine use. 5
  6. 6. Antimuscarinics: absorption of ketoconazole reduced by antimuscarinics;ketoconazole increases plasma concentration of darifenacin—avoid concomitantuse; manufacturer of fesoterodine advises dose reduction when ketoconazolegiven with fesoterodine —consult fesoterodine product literature; ketoconazoleincreases plasma concentration of solifenacin; avoidance of ketoconazole advisedby manufacturer of tolterodine.Antipsychotics: ketoconazole inhibits metabolism of aripiprazole (reduce dose ofaripiprazole); increased risk of ventricular arrhythmias when imidazoles given with.pimozide—avoid concomitant use; imidazoles possibly increase plasmaconcentration of quetiapine (reduce dose of quetiapine); increased risk ofventricular arrhythmias when ketoconazole given with sertindole—avoidconcomitant use; possible increased risk of ventricular arrhythmias whenimidazoles given with sertindole—avoid concomitant use.Antivirals: plasma concentration of both drugs increased when ketoconazolegiven with darunavir; plasma concentration of ketoconazole increased byfosamprenavir; ketoconazole increases plasma concentration of indinavir andmaraviroc (consider reducing dose of indinavir and maraviroc); plasmaconcentration of ketoconazole reduced by nevirapine—avoid concomitant use;combination of ketoconazole with ritonavir may increase plasma concentration ofeither drug (or both); ketoconazole increases plasma concentration of saquinavir;imidazoles possibly increase plasma concentration of saquinavir.Cytotoxics: ketoconazole inhibits metabolism of erlotinib and sunitinib (increasedplasma concentration); ketoconazole increases plasma concentration ofbortezomib and imatinib; ketoconazole increases plasma concentration of lapatiniband nilotinib— avoid concomitant use; ketoconazole increases plasmaconcentration of active metabolite of temsirolimus—avoid concomitant use; in vitrostudies suggest a possible interaction between ketoconazole and docetaxel(consult docetaxel product literature); ketoconazole reduces plasma concentrationof irinotecan (but concentration of active metabolite of irinotecan increased)—avoid concomitant use.Diuretics: ketoconazole increases plasma concentration of eplerenone—avoidconcomitant use.Ergot Alkaloids: increased risk of ergotism when imidazoles given withergotamine and methysergide — avoid concomitant use.5HT Agonists: ketoconazole increases plasma concentration of almotriptan(increased risk of toxicity); ketoconazole increases plasma concentration ofeletriptan (risk of toxicity)—avoid concomitant use.Ivabradine: ketoconazole increases plasma concentration of ivabradine—avoidconcomitant use.Lipid-regulating Drugs: possible increased risk of myopathy when imidazolesgiven with atorvastatin or simvastatin; increased risk of myopathy whenketoconazole given with .simvastatin (avoid concomitant use); possible increasedrisk of myopathy when miconazole given with .simvastatin—avoid concomitantuse. 6
  7. 7. Sirolimus: ketoconazole increases plasma concentration of sirolimus—avoidconcomitant use; miconazole increases plasma concentration of sirolimus.Vardenafil: ketoconazole increases plasma concentration of vardenafil—avoidconcomitant use.9.ANTI FUNGALS TRIAZOLEAnti-arrhythmics: manufacturer of itraconazole advises avoid concomitant usewith disopyramide.Antibacterials: plasma concentration of itraconazole increased by clarithromycin;triazoles possibly increase plasma concentration of rifabutin (increased risk ofuveitis—reduce rifabutin dose); posaconazole increases plasma concentration ofrifabutin (also plasma concentration of posaconazole reduced); voriconazoleincreases plasma concentration of rifabutin, also rifabutin reduces plasmaconcentration of voriconazole (increase dose of voriconazole and also monitor forrifabutin toxicity); fluconazole increases plasma concentration of rifabutin(increased risk of uveitis—reduce rifabutindose); plasma concentration ofitraconazole reduced by rifabutin—avoid concomitant use; plasma concentration ofposaconazole reduced by rifampicin; plasma concentration of voriconazole reducedby rifampicin—avoid concomitant use; metabolism of fluconazole and itraconazoleaccelerated by rifampicin (reduced plasma concentration).Antidepressants: avoidance of triazoles advised by manufacturer of reboxetine;plasma concentration of voriconazole reduced by .St John’s wort—avoidconcomitant use of midazolam (risk of prolonged sedation); itraconazole increasesplasma concentration of buspirone (reduce dose of buspirone).Antiepileptics: plasma concentration of itraconazole and posaconazole possiblyreduced by carbamazepine; fluconazole possibly increases plasma concentration ofcarbamazepine; plasma concentration of voriconazole possibly reduced bycarbamazepine and primidone—avoid concomitant use; voriconazole increasesplasma concentration of phenytoin, also phenytoin reduces plasma concentrationof voriconazole (increase dose of voriconazole and also monitor for phenytointoxicity); plasma concentration of posaconazole reduced by phenytoin; plasmaconcentration of itraconazole reduced by phenytoin—avoid concomitant use;fluconazole increases plasma concentration of phenytoin (consider reducing doseof phenytoin); plasma concentration of posaconazole possibly reduced byprimidone.Antihistamines: itraconazole inhibits metabolism of mizolastine—avoidconcomitant use .Antimalarials: avoidance of triazoles advised by manufacturer of artemether/lumefantrine.Antipsychotics: itraconazole possibly inhibits metabolism of aripiprazole (reducedose of aripiprazole); increased risk of ventricular arrhythmias when triazolesgiven with pimozide—avoid concomitant use; triazoles possibly increase plasmaconcentration of quetiapine (reduce dose of quetiapine); possible increased risk ofventricular arrhythmias when triazoles given with sertindole—avoid concomitant 7
  8. 8. use; increased risk of ventricular arrhythmias when itraconazole given withsertindole —avoid concomitant use.Antivirals: posaconazole increases plasma concentration of atazanavir; plasmaconcentration of itraconazole and posaconazole reduced by efavirenz; plasmaconcentration of voriconazole reduced by efavirenz, also plasma concentration ofefavirenz increased (consider increasing voriconazole dose and reducing efavirenzdose); plasma concentration of itraconazole possibly increased by fosamprenavir;itraconazole increases plasma concentration of indinavir (consider reducing dose ofindinavir); fluconazole increases plasma concentration of nevirapine, ritonavir andtipranavir; plasma concentration of voriconazole reduced by ritonavir—avoidconcomitant use; combination of itraconazole with ritonavir may increase plasmaconcentration of either drug (or both); triazoles possibly increase plasmaconcentration of saquinavir; fluconazole increases plasma concentration ofzidovudine (increased risk of toxicity).Bosentan: fluconazole possibly increases plasma concentration of bosentan—avoid concomitant use; itraconazole possibly increases plasma concentration ofbosentan.Cytotoxics: itraconazole inhibits metabolism of busulfan (increased risk oftoxicity); itraconazole possibly increases side-effects of cyclophosphamide;avoidance of itraconazole, posaconazole and voriconazole advised by manufacturerof lapatinib; avoidance of itraconazole and voriconazole advised by manufacturerof nilotinib; posaconazole possibly inhibits metabolism of vinblastine andvincristine (increased risk of neurotoxicity); itraconazole possibly inhibitsmetabolism of vincristine (increased risk of neurotoxicity).Diuretics: fluconazole increases plasma concentration of eplerenone (reduce doseof eplerenone); itraconazole increases plasma concentration of eplerenone—avoidconcomitant use; plasma concentration of fluconazole increased byhydrochlorothiazideErgot Alkaloids: increased risk of ergotism when triazoles given with ergotamineand methysergide— avoid concomitant use.5HT Agonists: itraconazole increases plasma concentration of eletriptan (risk oftoxicity)—avoid concomitant use.Ivabradine: fluconazole increases plasma concentration of ivabradine—reduceinitial dose of ivabradine; itraconazole possibly increases plasma concentration ofivabradine—avoid concomitant use.Lipid-regulating Drugs: possible increased risk of myopathy when triazolesgiven with atorvastatin or simvastatin; increased risk of myopathy whenitraconazole or posaconazole given with atorvastatin (avoid concomitant use);fluconazole increases plasma concentration of fluvastatin; increased risk ofmyopathy when itraconazole or posaconazole given with simvastatin (avoidconcomitant use).Sirolimus: posaconazole possibly increases plasma concentration of sirolimus;itraconazole and voriconazole increase plasma concentration of sirolimus— avoidconcomitant use. 8
  9. 9. Vardenafil: itraconazole possibly increases plasma concentration of vardenafil—avoid concomitant use.10.ANTI HISTAMINESAnti-arrhythmics: increased risk of ventricular arrhythmias when mizolastinegiven with .amiodarone, disopyramide, flecainide or propafenone—avoid concomitant use.Antibacterials: manufacturer of loratadine advises plasma concentration possiblyincreased by erythromycin; metabolism of mizolastine inhibited by erythromycin—avoid concomitant use; increased risk of ventricular arrhythmias when mizolastinegiven with moxifloxacin—avoid concomitant use; metabolism of mizolastinepossibly inhibited by macrolides (avoid concomitant use).Antidiabetics: thrombocyte count depressed when ketotifen given withmetformin (manufacturer of ketotifen advises avoid concomitant use).Antifungals: manufacturer of loratadine advises plasma concentration possiblyincreased by ketoconazole; metabolism of mizolastine inhibited by itraconazole orketoconazole—avoid concomitant use; metabolism of mizolastine possibly inhibitedby imidazoles (avoid concomitant use).Beta-blockers: increased risk of ventricular arrhythmias when mizolastine givenwith sotalol—avoid concomitant use.11.ANTIMUSCARICSAntibacterials: manufacturer of fesoterodine advises dose reduction whenfesoterodine given with clarithromycin and telithromycin—consult fesoterodineproduct literature; manufacturer of tolterodine advises avoid concomitant use withclarithromycin and erythromycin; plasma concentration of darifenacin possiblyincreased by erythromycin; plasma concentration of active metabolite ofesoterodine reduced by rifampicin.Antifungals: antimuscarinics reduce absorption of ketoconazole; manufacturer offesoterodine advises dose reduction when fesoterodine given with itraconazole andketoconazole—consult fesoterodine. product literature; plasma concentration ofdarifenacin increased by ketoconazole—avoid concomitant use; plasmaconcentration of solifenacin increased by itraconazole and ketoconazole;manufacturer of tolterodine advises avoid concomitant use with itraconazole andketoconazole; manufacturer of darifenacin advises avoid concomitant use withitraconazole.Calcium-channel Blockers: manufacturer of darifenacin advises avoidconcomitant use with verapamil.Ciclosporin: manufacturer of darifenacin advises avoid concomitant use withciclosporin.12.ANTI PSYCHOTICSAnalgesics: avoid concomitant use of clozapine with azapropazone (increased riskof agranulocytosis); possible severe drowsiness when haloperidol given with 9
  10. 10. indometacin; increased risk of convulsions when antipsychotics given withtramadol; enhanced hypotensive and sedative effects when antipsychotics givenwith opioid analgesics.Anti-arrhythmics: increased risk of ventricular arrhythmias when antipsychoticsthat prolong the QT interval given with anti-arrhythmics that prolong the QTinterval; increased risk of ventricular arrhythmias when amisulpride, haloperidol,phenothiazines, pimozide, sertindole or zuclopenthixol given with amiodarone—avoid concomitant use; increased risk of ventricular arrhythmias when benperidolgiven with amiodarone—manufacturer of benperidol advises avoid concomitantuse; increased risk of ventricular arrhythmias when sulpiride given withamiodarone or disopyramide; increased risk of ventricular arrhythmias whenamisulpride, pimozide, sertindole or zuclopenthixol given with disopyramide—avoidconcomitant use; increased risk of ventricular arrhythmias when phenothiazinesgiven with disopyramide; increased risk of arrhythmias when clozapine given withflecainide.Antibacterials: increased risk of ventricular arrhythmias when pimozide givenwith clarithromycin, moxifloxacin or telithromycin—avoid concomitant use;increased risk of ventricular arrhythmias when sertindole given with erythromycinor moxifloxacin—avoid concomitant use; increased risk of ventricular arrhythmiaswhen amisulpride or zuclopenthixol given with parenteral erythromycin—avoidconcomitant use; plasma concentration of clozapine possibly increased byerythromycin (possible increased risk of convulsions); possible increased risk ofventricular arrhythmias when pimozide given with erythromycin—avoidconcomitant use; increased risk of ventricular arrhythmias when sulpiride givenwith parenteral erythromycin; plasma concentration of clozapine increased byciprofloxacin; plasma concentration of olanzapine possibly increased byciprofloxacin; increased risk of ventricular arrhythmias when haloperidol,phenothiazines or zuclopenthixol given with moxifloxacin—avoid concomitant use;increased risk of ventricular arrhythmias when benperidol given with moxifloxacin— manufacturer of benperidol advises avoid concomitant use; plasmaconcentration of aripiprazole possibly reduced by rifabutin and rifampicin—increasedose of aripiprazole; plasma concentration of clozapine possibly reduced byrifampicin; metabolism of haloperidol accelerated by rifampicin (reduced plasmaconcentration); avoid concomitant use of clozapine with chloramphenicol orsulphonamides (increased risk of agranulocytosis); plasma concentration ofquetiapine possibly increased by macrolides (reduce dose of quetiapine); possibleincreased risk of ventricular arrhythmias when sertindole given with macrolides—avoid concomitant use.Antidepressants: plasma concentration of clozapine possibly increased bycitalopram (increased risk of toxicity); metabolism of aripiprazole possiblyinhibited by fluoxetine and paroxetine (reduce dose of aripiprazole); plasmaconcentration of clozapine, haloperidol, risperidone, sertindole and zotepineincreased by fluoxetine; plasma concentration of clozapine and olanzapineincreased by fluvoxamine; plasma concentration of clozapine and sertindole 10
  11. 11. increased by paroxetine; plasma concentration of risperidone possibly increased byparoxetine (increased risk of toxicity); metabolism of perphenazine inhibited byparoxetine (reduce dose of perphenazine); plasma concentration of clozapineincreased by sertraline and venlafaxine; plasma concentration of haloperidolincreased by venlafaxine; clozapine possibly increases CNS effects of MAOIs;plasma concentration of pimozide possibly increased by SSRIs (increased risk ofventricular arrhythmias—avoid concomitant use); plasma concentration ofaripiprazole possibly reduced by St John’s wort—increase dose of aripiprazole;antipsychotics increase plasma concentration of .tricyclics—possibly increasedrisk of ventricular arrhythmias; increased risk of antimuscarinic side-effects whenphenothiazines given with tricyclics; increased risk of ventricular arrhythmiaswhen pimozide given with tricyclics—avoid concomitant use; possibly increasedantimuscarinic side-effects when clozapine given with tricyclics.Antifungals: metabolism of aripiprazole inhibited by ketoconazole (reduce dose ofaripiprazole); increased risk of ventricular arrhythmias whensertindole given withitraconazole or ketoconazole—avoid concomitant use; metabolism of aripiprazolepossibly inhibited by itraconazole (reduce dose of aripiprazole); possible increasedrisk of ventricular arrhythmias when sertindole given with imidazoles or .triazoles—avoid concomitant use; plasma concentration of quetiapine possibly increased byimidazoles and triazoles (reduce dose of quetiapine); increased risk of ventriculararrhythmias when pimozide given with imidazoles or triazoles—avoid concomitantuse .Antimalarials: avoidance of antipsychotics advised by manufacturer ofartemether/lumefantrine; increased risk of ventricular arrhythmias when pimozidegiven with mefloquine or quinine—avoid concomitant use.Antipsychotics: avoid concomitant use of clozapine with depot formulation offlupentixol, fluphenazine, haloperidol, pipotiazine, risperidone or zuclopenthixol ascannot be withdrawn quickly if neutropenia occurs; increased risk of ventriculararrhythmias when sulpiride given with haloperidol; increased risk of ventriculararrhythmias when sertindole given with amisulpride—avoid concomitant use;increased risk of ventricular arrhythmias when pimozide given with phenothiazines— avoid concomitant use; increased risk of ventricular arrhythmias when pimozidegiven with sulpiride.Antivirals: plasma concentration of pimozide possibly increased by atazanavir—avoid concomitant use; metabolism of aripiprazole possibly inhibited byatazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir(reduce dose of aripiprazole); plasma concentration of pimozide possibly increasedby efavirenz, indinavir, nelfinavir and saquinavir (increased risk of ventriculararrhythmias—avoid concomitant use); plasma concentration of aripiprazolepossibly reduced by efavirenz and nevirapine—increase dose of aripiprazole;plasma concentration of pimozide and sertindole increased by fosamprenavir(increased risk of ventricular arrhythmias—avoid concomitant use); plasmaconcentration of clozapine possibly increased by fosamprenavir; plasmaconcentration of sertindole increased by indinavir, lopinavir, nelfinavir, ritonavir 11
  12. 12. and saquinavir (increased risk of ventricular arrhythmias—avoid concomitant use);plasma concentration of olanzapine reduced by ritonavir— consider increasingdose of olanzapine; plasma concentration of clozapine increased by ritonavir(increased risk of toxicity)—avoid concomitant use; plasma concentration ofantipsychotics possibly increased by ritonavir; plasma concentration of pimozideincreased by ritonavir (increased risk of ventricular arrhythmias—avoidconcomitant use).Aprepitant: avoidance of pimozide advised by manufacturer of aprepitant.Beta-blockers: enhanced hypotensive effect when phenothiazines given withbeta-blockers; plasma concentration of both drugs may increase whenchlorpromazine given with propranolol; increased risk of ventricular arrhythmiaswhen amisulpride, phenothiazines, pimozide, sertindole or sulpiride given withsotalol; increased risk of ventricular arrhythmias when zuclopenthixol given withsotalol—avoid concomitant use.Cytotoxics: avoid concomitant use of clozapine with cytotoxics (increased risk ofagranulocytosis); avoidance of pimozide advised by manufacturer of lapatinib.Desferrioxamine: manufacturer of levomepromazine (methotrimeprazine)advises avoid concomitant use with desferrioxamine; avoidance ofprochlorperazine advised by manufacturer of desferrioxamine.Diuretics: risk of ventricular arrhythmias with amisulpride or sertindole increasedby hypokalaemia caused by diuretics; risk of ventricular arrhythmias with pimozideincreased by hypokalaemia caused by diuretics (avoid concomitant use); enhancedhypotensive effect when phenothiazines given with diuretics.Ivabradine: increased risk of ventricular arrhythmias when pimozide or sertindolegiven with ivabradineLithium: increased risk of ventricular arrhythmias when sertindole given withlithium—avoid concomitant use; increased risk of extrapyramidal side-effects andpossibly neurotoxicity when clozapine, flupentixol, haloperidol, phenothiazines orzuclopenthixol given with lithium; increased risk of extrapyramidal sideeffectswhen sulpiride given with lithium.Penicillamine: avoid concomitant use of clozapine with penicillamine (increasedrisk of agranulocytosis)Pentamidine Isetionate: increased risk of ventricular arrhythmias whenamisulpride given with pentamidine isetionate—avoid concomitant use; increasedrisk of ventricular arrhythmias when phenothiazines given with pentamidineisetionateSibutramine: increased risk of CNS toxicity when antipsychotics given withsibutramine (manufacturer of sibutramine advises avoid concomitant use)Ulcer-healing Drugs: effects of antipsychotics, chlorpromazine and clozapinepossibly enhanced by cimetidine; increased risk of ventricular arrhythmias whensertindole given with cimetidine—avoid concomitant use; plasma concentration ofclozapine possibly reduced by omeprazole; absorption of sulpiride reduced bysucralfate. 12
  13. 13. 13.ANXIOLYTICS AND HYPNOTICSAntibacterials: metabolism of midazolam inhibited by clarithromycin,erythromycin, quinupristin/ dalfopristin and .telithromycin (increased plasmaconcentration with increased sedation); plasma concentration of buspironeincreased by erythromycin (reduce dose of buspirone); metabolism of zopicloneinhibited by erythromycin and quinupristin/dalfopristin; metabolism ofbenzodiazepines possibly accelerated by rifampicin (reduced plasmaconcentration); metabolism of diazepam accelerated by rifampicin (reducedplasma concentration); metabolism of buspirone and zaleplon possibly acceleratedby rifampicin; metabolism of zolpidem accelerated by rifampicin (reduced plasmaconcentration and reduced effect); plasma concentration of zopiclone significantlyreduced by rifampicin; metabolism of diazepam inhibited by isoniazid.Antidepressants: plasma concentration of melatonin increased by fluvoxamine—avoid concomitant use; plasma concentration of some benzodiazepines increasedby fluvoxamine; sedative effects possibly increased when zolpidem given withsertraline; manufacturer of buspirone advises avoid concomitant use with MAOIs;plasma concentration of oral midazolam possibly reduced by St John’s wort;increased sedative effect when anxiolytics and hypnotics given with mirtazapine,tricyclic-related antidepressants or tricyclics.Antifungals: plasma concentration of alprazolam increased by itraconazole andketoconazole; plasma concentration of midazolam increased by fluconazole,itraconazole and ketoconazole (risk of prolonged sedation); plasma concentrationof buspirone increased by itraconazole (reduce dose of buspirone); plasmaconcentration of midazolam increased by posaconazole.Antipsychotics: increased sedative effect when anxiolytics and hypnotics givenwith antipsychotics; buspirone increases plasma concentration of haloperidol;increased risk of hypotension, bradycardia and respiratory depression whenparenteral benzodiazepines given with intramuscular olanzapine; diazepamincreases plasma concentration of zotepine.Antivirals: plasma concentration of midazolam possibly increased by .atazanavir—avoid concomitant use oforal midazolam; increased risk of prolongedsedation when midazolam given with efavirenz— avoid concomitant use; increasedrisk of prolonged sedation and respiratory depression when alprazolam,clonazepam, diazepam, flurazepam or midazolam given with fosamprenavir;plasma concentration of midazolam possibly increased by indinavir, nelfinavir andritonavir (risk of prolonged sedation—avoid concomitant use of oral midazolam);increased risk of prolonged sedation when alprazolam given with .indinavir—avoidconcomitant use; plasma concentration of alprazolam, diazepam, flurazepam andzolpidem possibly increased by ritonavir (risk of extreme sedation and respiratorydepression —avoid concomitant use); plasma concentration of anxiolytics andhypnotics possibly increased by ritonavir; plasma concentration of buspironeincreased by ritonavir (increased risk of toxicity); plasma concentration ofmidazolam increased by saquinavir (risk of prolonged sedation—avoid concomitantuse of oral midazolam). 13
  14. 14. Sodium Oxybate: benzodiazepines enhance effects of .sodium oxybate (avoidconcomitant use).14.APRIPITANTAntidepressants: manufacturer of aprepitant advises avoid concomitant use withSt John’s wort.Antipsychotics: manufacturer of aprepitant advises avoid concomitant use withpimozide.Oestrogens: aprepitant possibly causes contraceptive failure of hormonalcontraceptives containing oestrogens (alternative contraception recommended)Progestogens: aprepitant possibly causes contraceptive failure of hormonalcontraceptives containing progestogens (alternative contraception recommended).15.ARTEMETHER WITH LUMIFANTINEAnti-arrhythmics: manufacturer of artemether/lumefantrine advises avoidconcomitant use with .amiodarone, disopyramide or flecainide (risk of ventriculararrhythmias).Antibacterials: manufacturer of artemether/lumefantrine advises avoidconcomitant use with macrolides and quinolones.Antidepressants: manufacturer of artemether/lumefantrine advises avoidconcomitant use with antidepressantsAntifungals: manufacturer of artemether/lumefantrine advises avoid concomitantuse with .imidazoles and triazolesAntimalarials: manufacturer of artemether/lumefantrine advises avoidconcomitant use with .antimalarials; increased risk of ventricular arrhythmiaswhen artemether/lumefantrine given with quinine.Antipsychotics: manufacturer of artemether/lumefantrine advises avoidconcomitant use with antipsychotics.Beta-blockers: manufacturer of artemether/lumefantrine advises avoidconcomitant use with metoprolol and sotalol.Grapefruit Juice: plasma concentration of artemether/ lumefantrine possiblyincreased by grapefruit juice.Ulcer-healing Drugs: manufacturer of artemether/ lumefantrine advises avoidconcomitant use withcimetidine.Analgesics: avoid concomitant use of aspirin with NSAIDs (increased side-effects); antiplatelet effect of aspirin possibly reduced by ibuprofen.Antacids: excretion of aspirin increased by alkaline urine due to some antacids.Anticoagulants: increased risk of bleeding when aspirin given with coumarins orphenindione (due to antiplatelet effect); aspirin enhances anticoagulant effect ofheparins.Antidepressants: increased risk of bleeding when aspirin given with SSRIs orvenlafaxine.Antiepileptics: aspirin enhances effects of phenytoin and valproate. 14
  15. 15. Cytotoxics: aspirin reduces excretion of methotrexate (increased risk oftoxicity)—but for concomitant use in rheumatic disease.16.ATAZANAVIRAnti-arrhythmics: atazanavir possibly increases plasma concentration ofamiodarone and .lidocaine (lignocaine).Antibacterials: plasma concentration of both drugs increased when atazanavirgiven with clarithromycin; atazanavir increases plasma concentration of rifabutin(reduce dose of rifabutin); plasma concentration of atazanavir reduced byrifampicin—avoid concomitant use; avoidance of concomitant atazanavir in severerenal and hepatic impairment advised by manufacturer of telithromycin.Antidepressants: plasma concentration of atazanavir reduced by St John’s wort—avoid concomitant use .Antifungals: plasma concentration of atazanavir increased by posaconazoleAntimalarials: caution with atazanavir advised by manufacturer of artemether/lumefantrine.Antimuscarinics: avoidance of atazanavir advised by manufactur of darifenacin;manufacturer of fesoterodine advises dose reduction when atazanavir given withfesoterodine—consult fesoterodine product literature .Antipsychotics: atazanavir possibly inhibits metabolism of aripiprazole (reducedose of aripiprazole); atazanavir possibly increases plasma concentration of.pimozide—avoid concomitant use.Antivirals: manufacturer of atazanavir advises avoid concomitant use with.efavirenz (plasma concentration of atazanavir reduced); avoid concomitant use ofatazanavir with indinavir; atazanavir increases plasma concentration of maraviroc(consider reducing dose of maraviroc); plasma concentration of atazanavirpossibly reduced by nevirapine—avoid concomitant use; atazanavir increasesplasma concentration of saquinavir; plasma concentration of atazanavir reducedby tenofovir, also plasma concentration of tenofovir possibly increased; atazanavirincreases plasma concentration of tipranavir (also plasma concentration ofatazanavir reduced).Anxiolytics and Hypnotics: atazanavir possibly increases plasma concentrationof midazolam— avoid concomitant use of oral midazolam.Calcium-channel Blockers: atazanavir increases plasma concentration ofdiltiazem (reduce dose of diltiazem); atazanavir possibly increases plasmaconcentration of verapamil.Ciclosporin: atazanavir possibly increases plasma concentration of ciclosporin.Cytotoxics: atazanavir possibly inhibits metabolism of .irinotecan (increased riskof toxicity).Ergot Alkaloids: atazanavir possibly increases plasma concentration of ergotalkaloids—avoid concomitant use.Lipid-regulating Drugs: possible increased risk of myopathy when atazanavirgiven with atorvastatin; possible increased risk of myopathy when atazanavir 15
  16. 16. given with rosuvastatin—avoid concomitant use; increased risk of myopathy whenatazanavir given with simvastatin (avoid concomitant use).Oestrogens: atazanavir increases plasma concentration of .ethinylestradiol—avoid concomitant use.Sildenafil: atazanavir possibly increases side-effects of sildenafilSirolimus: atazanavir possibly increases plasma concentration of sirolimusTacrolimus: atazanavir possibly increases plasma concentration of tacrolimusUlcer-healing Drugs: plasma concentration of atazanavir possibly reduced byhistamine H -antagonists; plasma concentration of atazanavir reduced by protonpump inhibitors.17.ATOMOXETINEAnalgesics: increased risk of ventricular arhythmias when atomoxetine given withmethadone; possible. increased risk of convulsions when atomoxetine given withtramadol.Anti-arrhythmics: increased risk of ventricular arrhythmias when atomoxetinegiven with amiodarone or disopyramideAntibacterials: increased risk of ventricular arrhythmias when atomoxetine givenwith parenteral erythromycin; increased risk of ventricular arrhythmias whenatomoxetine given with moxifloxacin.Antidepressants: metabolism of atomoxetine possibly inhibited by fluoxetine andparoxetine; possible increased risk of convulsions when atomoxetine given withantidepressants; atomoxetine should not be started until 2 weeks after stoppingMAOIs, also MAOIs should not be started until at least 2 weeks after stoppingatomoxetine; increased risk of ventricular arrhythmias when atomoxetine givenwith .tricyclics.Antimalarials: increased risk of ventricular arrhythmias when atomoxetine givenwith mefloquine . Antipsychotics: increased risk of ventricular arrhythmias whenatomoxetine given with .antipsychotics that prolong the QT interval.Beta-blockers: increased risk of ventricular arrhythmias when atomoxetine givenwith sotalol.Bupropion: possible increased risk of convulsions when atomoxetine given withbupropion.Diuretics: risk of ventricular arrhythmias with atomoxetine increased byhypokalaemia caused by diuretics.18.ATOVAQUONEAntibacterials: plasma concentration of atovaquone reduced by .rifabutin and.rifampicin (possible therapeutic failure of atovaquone); plasma concentrationof atovaquone reduced by tetracycline.19.AZATHIOPRINE 16
  17. 17. Allopurinol: enhanced effects and increased toxicity of azathioprine when givenwith allopurinol (reduce dose of azathioprine to one quarter of usual dose).Aminosalicylates: possible increased risk of leucopenia when azathioprine givenwith aminosalicylates.Antibacterials: increased risk of haematological toxicity when azathioprine givenwith sulfamethoxazole (as co-trimoxazole); increased risk of haematologicaltoxicity when azathioprine given with trimethoprim (also with co-trimoxazole).Anticoagulants: azathioprine possibly reduces anticoagulant effect of coumarinsAntiepileptics: cytotoxics possibly reduce absorption of phenytoin.Antipsychotics: avoid concomitant use of cytotoxics with clozapine (increasedrisk of agranulocytosis).20.AZTREONAMAnticoagulants: aztreonam possibly enhances anticoagulant effect of coumarins.20a.BARBITURATESAntibacterials: barbiturates accelerate metabolism of chloramphenicol,doxycycline and metronidazole (reduced plasma concentration); phenobarbitalpossibly reduces plasma concentration of rifampicin; phenobarbital reduces plasmaconcentration of telithromycin (avoid during and for 2 weeks after phenobarbital).Anticoagulants: barbiturates accelerate metabolism of coumarins (reducedanticoagulant effect).Antidepressants: phenobarbital reduces plasma concentration of paroxetine;phenobarbital accelerates metabolism of mianserin (reduced plasmaconcentration); anticonvulsant effect of barbiturates possibly antagonised byMAOIs and tricyclic-related antidepressants (convulsive threshold lowered);anticonvulsant effect of barbiturates antagonised by SSRIs (convulsive thresholdlowered); avoid concomitant use of phenobarbital with .St John’s wort;anticonvulsant effect of barbiturates antagonised by tricyclics (convulsivethreshold lowered), also metabolism of tricyclics possibly accelerated (reducedplasma concentration).Antifungals: phenobarbital possibly reduces plasma concentration of itraconazoleand .posaconazole; phenobarbital possibly reduces plasma concentration ofvoriconazole—avoid concomitant use; Phenobarbital reduces absorption ofgriseofulvin (reduced effect).Antipsychotics: anticonvulsant effect of barbiturates antagonised byantipsychotics (convulsive threshold lowered); phenobarbital acceleratesmetabolism of haloperidol (reduced plasma concentration); plasma concentrationof both drugs reduced when Phenobarbital given with chlorpromazine;Phenobarbital possibly reduces plasma concentration of aripiprazole—increasedose of aripiprazole.Antivirals: phenobarbital possibly reduces plasma concentration of abacavir,darunavir, fosamprenavir and lopinavir; avoidance of Phenobarbital advised bymanufacturer of etravirine; barbiturates possibly reduce plasma concentration of 17
  18. 18. indinavir, nelfinavir and saquinavir; Phenobarbital possibly reduces plasmaconcentration of indinavir, also plasma concentration of phenobarbital possiblyincreased.Calcium-channel Blockers: barbiturates reduce effects of .felodipine and.isradipine; barbiturates probably reduce effects of .dihydropyridines, .diltiazemand .verapamil.Ciclosporin: barbiturates accelerate metabolism of .ciclosporin (reduced effect)Corticosteroids: barbiturates accelerate metabolism of .corticosteroids (reducedeffect).Cytotoxics: phenobarbital possibly reduces plasma concentration of etoposide;phenobarbital reduces plasma concentration of irinotecan and its active Metabolite.Diuretics: phenobarbital reduces plasma concentration of .eplerenone—avoidconcomitant use; increased risk of osteomalacia when phenobarbital given withcarbonic anhydrase inhibitors.Oestrogens: barbiturates accelerate metabolism of .oestrogens (reducedcontraceptive effect.Progestogens: barbiturates accelerate metabolism of .progestogens (reducedcontraceptive effect.Sodium Oxybate: barbiturates enhance effects of sodium oxybate (avoidconcomitant use)Sympathomimetics: plasma concentration of phenobarbital possibly increased bymethylphenidate.Tacrolimus: phenobarbital reduces plasma concentration of .tacrolimus.21.BETA BLOCKERSAlpha-blockers: enhanced hypotensive effect when beta-blockers given with.alpha-blockers, also increased risk of first-dose hypotension with postsynapticalpha-blockers such as prazosin.Anaesthetics, Local: propranolol increases risk of .bupivacaine toxicity.Anti-arrhythmics: increased myocardial depression when beta-blockers givenwith .anti-arrhythmics; increased risk of ventricular arrhythmias when sotalolgiven with .amiodarone or .disopyramide—avoid concomitant use; increased riskof bradycardia, AV block and myocardial depression when beta-blockers given with.amiodarone; increased risk of myocardial depression and bradycardia when beta-blockers given with .flecainide; propranolol increases risk of .lidocaine (lignocaine)toxicity; plasma concentration of metoprolol and propranolol increased bypropafenone.Antibacterials: increased risk of ventricular arrhythmias when sotalol givenwith .moxifloxacin—avoid concomitant use; metabolism of bisoprolol andpropranolol accelerated by rifampicin (plasma concentration significantly reduced);plasma concentration of carvedilol, celiprolol and metoprolol reduced by rifampicin.Antidepressants: plasma concentration of metoprolol increased by citalopramand escitalopram; plasma concentration of propranolol increased by fluvoxamine; 18
  19. 19. plasma concentration of metoprolol possibly increased by paroxetine (enhancedeffect); labetalol and propranolol increase plasma concentration of imipramine;enhanced hypotensive effect when beta-blockers given with MAOIs; increased riskof ventricular arrhythmias when sotalol given with .tricyclics.Antihistamines: increased risk of ventricular arrhythmias when sotalol given with.mizolastine—avoid concomitant use.Antimalarials: avoidance of metoprolol and sotalol advised by manufacturer of.artemether/lumefantrine; increased risk of bradycardia when betablockers givenwith mefloquine.Antimuscarinics:increased risk of ventricular arrhythmias when sotalol givenwithtolterodine.Antipsychotics: plasma concentration of both drugs may increase whenpropranolol given with chlorpromazine; increased risk of ventricular arrhythmiaswhen sotalol given with .zuclopenthixol— avoid concomitant use; increased risk ofventricular arrhythmias when sotalol given with .amisulpride, .phenothiazines,pimozide, .sertindole or .sulpiride; enhanced hypotensive effect when betablockersgiven with phenothiazines.Antivirals: avoidance of metoprolol for heart failure advised by manufacturer of.tipranavir.Anxiolytics and Hypnotics: enhanced hypotensive effect when beta-blockersgiven with anxiolytics and hypnotics.Atomoxetine: increased risk of ventricular arrhythmias when sotalol given with.atomoxetine.Barbiturates: plasma concentration of metoprolol and timolol reduced by barbiturates;plasma concentration of propranolol possibly reduced bybarbiturates.Calcium-channel Blockers: enhanced hypotensive effect when beta-blockersgiven with calciumchannel blockers; possible severe hypotension and heart failurewhen beta-blockers given with .nifedipine; increased risk of AV block and bradycardia when beta-blockers given with .diltiazem; asystole, severe hypotension andheart failure when betablockers given with .verapamil.Ciclosporin: carvedilol increases plasma concentration of .ciclosporinClonidine: increased risk of withdrawal hypertension when beta-blockers givenwith .clonidine (withdraw beta-blockers several days before slowly withdrawingclonidine).Diuretics: enhanced hypotensive effect when betablockers given with diuretics;risk of ventricular arrhythmias with sotalol increased by hypokalaemia caused byloop diuretics or .thiazides and related diuretics.5HT Antagonists: increased risk of ventricular arrhythmias when sotalol givenwith .dolasetron—avoid concomitant use.Ivabradine: increased risk of ventricular arhythmias when sotalol with ivabradine.Methyldopa: enhanced hypotensive effect when betablockers given withmethyldopa.Moxisylyte (thymoxamine): possible severe postural hypotension when beta-blockers given with .moxisylyte. 19
  20. 20. Sympathomimetics: increased risk of severe hypertension and bradycardia whennon-cardioselective beta-blockers given with .adrenaline (epinephrine), alsoreponse to adrenaline (epinephrine) may be reduced; increased risk of severehypertension and bradycardia when non-cardioselective beta-blockers givenwith .dobutamine; possible increased risk of severe hypertension and bradycardiawhen noncardioselective beta-blockers given with .noradrenaline(norepinephrine).22.BEXAROTENEAntipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).Cardiac Glycosides: cytotoxics reduce absorption of digoxin tablets.Lipid-regulating Drugs: plasma concentration of bexarotene increased by.gemfibrozil—avoid concomitant use.23.BLEOMYCINAntipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).Cardiac Glycosides: cytotoxics reduce absorption of digoxin tabletsCytotoxics: increased pulmonary toxicity when bleomycin given with .cisplatin.24.BORTEZOMIBAntipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).25.BOSENTANAntibacterials: plasma concentration of bosentan reduced by .rifampicin—avoidconcomitant use.Anticoagulants: manufacturer of bosentan recommends monitoring anticoagulanteffect of coumarins.Antidiabetics: increased risk of hepatotoxicity when bosentan given with.glibenclamide—avoid concomitant use.Antifungals: plasma concentration of bosentan increased by ketoconazole;plasma concentration of bosentan possibly increased by .fluconazole—avoidconcomitant use; plasma concentration of bosentan possibly increased byitraconazole.Ciclosporin: plasma concentration of bosentan increased by .ciclosporin (alsoplasma concentration of ciclosporin reduced—avoid concomitant use).Oestrogens: bosentan possibly causes contraceptive failure of hormonalcontraceptives containing .oestrogens (alternative contraception recommended)Progestogens: bosentan possibly causes contraceptive failure of hormonalcontraceptives containing.progestogens (alternative contraception recommended).26.BROMOCRIPTINE 20
  21. 21. Sympathomimetics:risk of toxicity when bromocriptine given with isomethepteneor phenylpropanolamine.27.BUPIVACAINEBeta-blockers: increased risk of bupivacaine toxicity when given with .propranolol.28.BUPROPIONAntidepressants: bupropion possibly increases plasma concentration ofcitalopram; manufacturer of bupropion advises avoid for 2 weeks after stopping.MAOIs; manufacturer of bupropion advises avoidconcomitant use with.moclobemide.Antiepileptics: plasma concentration of bupropion reduced by carbamazepineand phenytoin; metabolism of bupropion inhibited by valproate.Antivirals: plasma concentration of bupropion increased or decreased by.ritonavir.29.BUSULPHANAntibacterials: plasma concentration of busulfan increased by .metronidazole(increased risk of toxicity).Antipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).30.CALCIUM CHANNEL BLOCKERSAlpha-blockers: enhanced hypotensive effect when calcium-channel blockersgiven with .alpha-blockers, also increased risk of first-dose hypotension withpost-synaptic alpha-blockers such as prazosin.Anaesthetics, General: enhanced hypotensive effect when calcium-channelblockers given with general anaesthetics or isoflurane; hypotensive effect ofverapamil.Anti-arrhythmics: increased risk of bradycardia, AV block and myocardialdepression when diltiazem or verapamil given with .amiodarone; increased risk ofmyocardial depression and asystole when verapamil given with .disopyramide or.flecainide.Antibacterials: metabolism of verapamil possibly inhibited by .clarithromycin and.erythromycin (increased risk of toxicity); metabolism of felodipine possiblyinhibited by erythromycin (increased plasma concentration); manufacturer oflercanidipine advises avoid concomitant use with erythromycin; metabolism ofdiltiazem, nifedipine, nimodipine and verapamil accelerated by .rifampicin (plasmaconcentration significantly reduced); metabolism of isradipine and nicardipinepossibly accelerated by .rifampicin (possible significantly reduced plasmaconcentration); plasma concentration of nifedipine increased by.quinupristin/dalfopristin. 21
  22. 22. Antiepileptics: effects of dihydropyridines, nicardipine and nifedipine probablyreduced by carbamazepine; effects of felodipine and isradipine reduced bycarbamazepine; diltiazem and verapamil enhance effects of .carbamazepine;effects of dihydropyridines, nicardipine and nifedipine probably reduced by.phenytoin; effects of felodipine, isradipine and verapamil reduced by phenytoin;diltiazem increases plasma concentration of .phenytoin but also effect of diltiazemreduced; effects of felodipine and isradipine reduced by .primidone; effects ofdihydropyridines, diltiazem and verapamil probably reduced by .primidone.Antifungals: metabolism of dihydropyridines possibly inhibited by itraconazoleand ketoconazole (increased plasma concentration); metabolism of felodipineinhibited by .itraconazole and .ketoconazole (increased plasma concentration);manufacturer of lercanidipine advises avoid concomitant use with itraconazole andketoconazole; negative inotropic effect possibly increased when calcium-channelblockers given with itraconazole; plasma concentration of nifedipine increased bymicafungin.Antivirals: plasma concentration of verapamil possibly increased by atazanavir;plasma concentration of diltiazem increased by .atazanavir (reduce dose ofdiltiazem); plasma concentration of diltiazem reduced by efavirenz; manufacturerof lercanidipine advises avoid concomitant use with ritonavir; plasmaconcentration of calcium-channel blockers possibly increased by .ritonavir.Barbiturates: effects of dihydropyridines, diltiazem and verapamil probablyreduced by .barbiturates; effects of felodipine and isradipine reduced by.barbiturates. calcium-channel blockers given with beta-blockers;increased risk of AV block and bradycardia when diltiazem given with .beta-blockers; asystole, severe hypotension and heart failure when verapamil givenwith .beta-blockers; possible severe hypotension and heart failure when nifedipinegiven with .beta-blockers.Cardiac Glycosides: nifedipine possibly increases plasma concentration of.digoxin; diltiazem, lercanidipine and nicardipine increase plasma concentrationof .digoxin; verapamil increases plasma concentration of .digoxin, also increasedrisk of AV block and bradycardia.Ciclosporin: diltiazem, nicardipine and verapamil increase plasma concentrationof .ciclosporin; combination of lercanidipine with .ciclosporin may increase plasmaconcentration of either drug (or both)—avoid concomitant use; plasmaconcentration of nifedipine possibly increased by ciclosporin (increased risk oftoxicity including gingival hyperplasia).Cilostazol: diltiazem increases plasma concentration of cilostazol—avoidconcomitant use.Ivabradine: diltiazem and verapamil increase plasma concentration ofivabradine—avoid concomitant useLipid-regulating Drugs: diltiazem increases plasma concentration of atorvastatinpossible increased risk of myopathy when diltiazem given with simvastatin;increased risk of myopathy when verapamil given with .simvastatin. 22
  23. 23. Magnesium (parenteral): profound hypotension reported with concomitant useof nifedipine and .parenteral magnesium in pre-eclampsia.Sirolimus: diltiazem increases plasma concentration of .sirolimus; plasmaconcentration of both drugs increased when verapamil given with .sirolimus.Tacrolimus: diltiazem and nifedipine increase plasma concentration of.tacrolimus; felodipine, nicardipine and verapamil possibly increase plasmaconcentration of tacrolimus.Theophylline: calcium-channel blockers possibly increase plasma concentration oftheophylline (enhance effect);diltiazem increases plasma concentration of theophylline; verapamil increases lasma concentration of .theophylline (enhanced effect).31.CARBAMAZEPINEAnalgesics: effects of carbamazepine enhanced by .dextropropoxyphene;carbamazepine reduces plasma concentration of methadone; carbamazepinereduces effects of tramadol; carbamazepine possibly accelerates metabolism ofparacetamol.Antibacterials: plasma concentration of carbamazepine increased byclarithromycin and erythromycin; plasma concentration of carbamazepine reducedby .rifabutin; carbamazepine accelerates metabolism of doxycycline (reducedeffect); plasma concentration of carbamazepine increased by isoniazid (alsopossibly increased isoniazid hepatotoxicity); carbamazepine reduces plasmaconcentration of telithromycin (avoid during & for 2 weeks after carbamazepine).Anticoagulants: carbamazepine accelerates metabolism of .coumarins (reducedanticoagulant effect).Antidepressants: plasma concentration of carbamazepine increased by.fluoxetine and .fluvoxamine; carbamazepine reduces plasma concentration ofmianserin, mirtazapine and paroxetine; manufacturer of carbamazepine advisesavoid for 2 weeks after stopping .MAOIs, also antagonism of anticonvulsant effect;anticonvulsant effect of antiepileptics possibly antagonised by MAOIs and tricyclic-related antidepressants (convulsive threshold lowered); anticonvulsant effect ofantiepileptics antagonised by .SSRIs and .tricyclics (convulsive threshold lowered);avoid concomitant use of antiepileptics with .St John’s wort; carbamazepineaccelerates metabolism of tricyclics (low plasma concentration & less effect).Antifungals: plasma concentration of carbamazepine possibly increased byfluconazole, ketoconazole and miconazole; carbamazepine possibly reducesplasma concentration of itraconazole and .posaconazole; carbamazepine possiblyreduces plasma concentration of .voriconazole—avoid concomitant use;carbamazepine possibly reduces plasma concentration of caspofungin—considerincreasing dose of caspofungin.Antimalarials: possible increased risk of convulsions when antiepileptics givenwith chloroquine and hydroxychloroquine; anticonvulsant effect of antiepilepticsantagonised by .mefloquine.Antipsychotics: anticonvulsant effect of carbamazepine antagonised byantipsychotics (convulsive threshold lowered); carbamazepine accelerates 23
  24. 24. metabolism of haloperidol, olanzapine, quetiapine, risperidone and sertindole(reduced plasma concentration); carbamazepine reduces plasma concentration ofaripiprazole—increase dose of aripiprazole; carbamazepine accelerates metabolismof .clozapine (reduced plasma concentration), also avoid concomitant use of drugswith substantial potential for causing agranulocytosis; carbamazepine reducesplasma concentration of paliperidone.Antivirals: carbamazepine possibly reduces plasma concentration of darunavir,fosamprenavir, lopinavir, nelfinavir, saquinavir and tipranavir; plasmaconcentration of both drugs reduced when carbamazepine given with efavirenz;avoidance of carbamazepine advised by manufacturer of etravirine;carbamazepine possibly reduces plasma concentration of indinavir, also plasmaconcentration of carbamazepine possibly increased; plasma concentration ofcarbamazepine possibly increased by .ritonavir.Calcium-channel Blockers: carbamazepine reduces effects of felodipine andisradipine; carbamazepine. probably reduces effects of dihydropyridines,nicardipine and nifedipine; effects of carbamazepine enhanced by .diltiazem and.verapamilCardiac Glycosides: carbamazepine accelerates metabolism of digitoxin (reducedeffect)Ciclosporin: carbamazepine accelerates metabolism of ciclosporin (reducedplasma concentration) Corticosteroids: carbamazepine accelerates metabolismof .corticosteroids (reduced effect).Cytotoxics: carbamazepine reduces plasma concentration of .imatinib andlapatinib—avoid concomitant use; carbamazepine reduces plasma concentration ofirinotecan and its active metabolite.Diuretics: increased risk of hyponatraemia when carbamazepine given withdiuretics; plasma concentration of carbamazepine increased by acetazolamide;carbamazepine reduce plasma concentration of eplerenone avoid concomitant use.Hormone Antagonists: metabolism of carbamazepine inhibited by .danazol(increased risk of toxicity); carbamazepine accelerates metabolism of gestrinone(reduced plasma concentration); carbamazepine possibly accelerates metabolismof toremifene (reduced plasma concentration).Oestrogens: carbamazepine accelerates metabolism of oestrogens (reducedcontraceptive effect.Progestogens: carbamazepine accelerates metabolism of .progestogens (reducedcontraceptive effect.Ulcer-healing Drugs: metabolism of carbamazepine inhibited by .cimetidine(increased plasma concentration).32.CARDIAC GLYCOSIDESAnti-arrhythmics: plasma concentration of digoxin increased by .amiodarone andpropafenone (halve dose of digoxin).Antidepressants: plasma concentration of digoxin reduced by .St John’s wort—avoid concomitant use. 24
  25. 25. Antifungals: increased cardiac toxicity with cardiac glycosides if hypokalaemiaoccurs with amphotericin; plasma concentration of digoxin increased byitraconazole.Antimalarials: plasma concentration of digoxin possibly increased by .chloroquineand hydroxychloroquine; possible increased risk of bradycardia when digoxin givenwith mefloquine; plasma concentration of digoxin increased by .quinine.Calcium-channel Blockers: plasma concentration of digoxin increased bydiltiazem, .lercanidipine and nicardipine; plasma concentration of digoxin possiblyincreased by .nifedipine; plasma concentration of digoxin increased by .verapamil,also increased risk of AV block and bradycardia.Ciclosporin: plasma concentration of digoxin increased by .ciclosporin (increasedrisk of toxicity).Corticosteroids: increased risk of hypokalaemia when cardiac glycosides givenwith corticosteroids.Cytotoxics: absorption of digoxin tablets reduced by cytotoxicsDiuretics: increased cardiac toxicity with cardiac glycosides if hypokalaemiaoccurs with acetazolamide, .loop diuretics or .thiazides and related diuretics;plasma concentration of digoxin possibly increased by potassium canrenoate;plasma concentration of digitoxin possibly affected by spironolactone; plasmaconcentration of digoxin increased by .spironolactone.33.CARMUSTINEAntipsychotics: avoid concomitant use of cytotoxics with .clozapine (increased riskof agranulocytosis).34.CASPOFUNGINCiclosporin: plasma concentration of caspofungin increased by .ciclosporin(manufacturer of caspofungin recommends monitoring liver enzymes)Corticosteroids: plasma concentration of caspofungin.possibly reduced by dexamethasone—consider increasing dose of caspofunginTacrolimus: caspofungin reduces plasma concentration of .tacrolimus.35.CEPHALOSPORINSAnticoagulants: cephalosporins possibly enhance anticoagulant effect ofcoumarins.Anticoagulants: chloramphenicol enhances anticoagulant effect of .coumarinsAntidiabetics: chloramphenicol enhances effects of sulphonylureas.Antiepileptics: chloramphenicol increases plasma concentration of .phenytoin(increased risk of toxicity); metabolism of chloramphenicol accelerated by.primidone (reduced plasma concentration).Antipsychotics: avoid concomitant use of chloramphenicol with .clozapine(increased risk of agranulocytosis).Barbiturates: metabolism of chloramphenicol accelerated by .barbiturates(reduced plasma concentration). 25
  26. 26. Ciclosporin: chloramphenicol possibly increases plasma concentration ofciclosporin.Tacrolimus: chloramphenicol possibly increases plasma concentration oftacrolimus.36.CHLOROQUINE AND HYDROXY CHLOROQUINEAnti-arrhythmics: increased risk of ventricular arrhythmias when chloroquineand hydroxychloroquine given with .amiodarone—avoid concomitant use.Antibacterials: increased risk of ventricular arrhythmias when chloroquine andhydroxychloroquine given with .moxifloxacin—avoid concomitant use.Antimalarials: avoidance of antimalarials advised by manufacturer ofartemether/lumefantrine; increased risk of convulsions when chloroquine andhydroxychloroquine given with .mefloquineCardiac Glycosides: chloroquine and hydroxychloroquine possibly increaseplasma concentration of digoxin.Ciclosporin: chloroquine and hydroxychloroquine increase plasma concentrationof .ciclosporin (increased risk of toxicity).37.CICLOSPORINACE Inhibitors: increased risk of hyperkalaemia when ciclosporin given with .ACEinhibitors.Analgesics: increased risk of nephrotoxicity when ciclosporin given with .NSAIDs;ciclosporin increases plasma concentration of .diclofenac (halve dose ofdiclofenac). Angiotensin-II Receptor Antagonists: increased risk of hyperkalaemiawhen ciclosporin given with .angiotensin- II receptor antagonists.Antibacterials: metabolism of ciclosporin inhibited by clarithromycin anderythromycin (increased plasma concentration); metabolism of ciclosporinaccelerated by .rifampicin (reduced plasma concentration); plasma concentrationof ciclosporin possibly reduced by .sulfadiazine; plasma concentration ofciclosporin possibly increased by .chloramphenicol, doxycycline and .telithromycin;increased risk of nephrotoxicity when ciclosporin given with aminoglycosides,.polymyxins, .quinolones, sulphonamides or .vancomycin; increased risk ofmyopathy when ciclosporin given with .daptomycin (preferably avoid concomitantuse); metabolism of ciclosporin possibly inhibited by .macrolides (increasedplasma concentration); plasma concentration of ciclosporin increased by.quinupristin/ dalfopristin; increased risk of nephrotoxicity when ciclosporin givenwith .trimethoprim, also plasma concentration of ciclosporin reduced byintravenous trimethoprim.Antidepressants: plasma concentration of ciclosporin reduced by .St John’s wort—avoid concomitant use.Antidiabetics: ciclosporin possibly enhances hypoglycaemic effect of repaglinideAntiepileptics: metabolism of ciclosporin accelerated by .carbamazepine and.phenytoin (reduced plasma concentration); plasma concentration of ciclosporin 26
  27. 27. possibly reduced by oxcarbazepine; metabolism of ciclosporin accelerated byprimidone (reduced effect).Antifungals: metabolism of ciclosporin inhibited by fluconazole, .itraconazole,.ketoconazole, posaconazole and .voriconazole (increased plasma concentration);metabolism of ciclosporin possibly inhibited by .miconazole (increased plasmaconcentration); increased risk of nephrotoxicity when ciclosporin given with.amphotericin; ciclosporin increases plasma concentration of .caspofungin(manufacturer of caspofungin recommends monitoring liver enzymes); plasmaconcentration of ciclosporin possibly reduced by griseofulvin; plasma concentrationof ciclosporin possibly increased by micafungin.Antimalarials: plasma concentration of ciclosporin increased by .chloroquine andhydroxychloroquine (increased risk of toxicity).Antimuscarinics: avoidance of ciclosporin advised by manufacturer of darifenacinAntivirals: increased risk of nephrotoxicity when ciclosporin given with aciclovir;plasma concentration of ciclosporin possibly increased by .atazanavir, nelfinavirand .ritonavir; plasma concentration of ciclosporin increased by .indinavir; plasmaconcentration of both drugs increased when ciclosporin given with .saquinavir.Barbiturates: metabolism of ciclosporin accelerated by barbiturates (reducedeffect).Beta-blockers: plasma concentration of ciclosporin increased by .carvedilolBile Acids: absorption of ciclosporin increased by ursodeoxycholic acid.Bosentan: ciclosporin increases plasma concentration of .bosentan (also plasmaconcentration of ciclosporin reduced—avoid concomitant use).Calcium-channel Blockers: combination of ciclosporin with .lercanidipine mayincrease plasma concentrationof either drug (or both)—avoid concomitant use;plasma concentration of ciclosporin increased by diltiazem, .nicardipine andverapamil; ciclosporin possibly increases plasma concentration of nifedipine(increased risk of toxicity including gingival hyperplasia).Cardiac Glycosides: ciclosporin increases plasma oncentration of .digoxin(increased risk of toxicity).Colchicine: possible increased risk of nephrotoxicity and myotoxicity whenciclosporin given with colchicine (increased plasma concentration of ciclosporin).Corticosteroids: plasma concentration of ciclosporin increased by high-dosemethylprednisolone (risk of convulsions); ciclosporin increases plasmaconcentration of prednisolone.Cytotoxics: increased risk of nephrotoxicity when ciclosporin given withmelphalan; increased risk of neurotoxicity when ciclosporin given with doxorubicin;risk of toxicity when ciclosporin given with .methotrexate; plasma concentration ofciclosporin possibly increased by imatinib; in vitro studiessuggest a possible interaction between ciclosporin and docetaxel (consultdocetaxel product literature); ciclosporin possibly increases plasma concentrationof etoposide (increased risk of toxicity). 27
  28. 28. Diuretics: increased risk of hyperkalaemia when ciclosporin given with potassium-sparing diuretics and aldosterone antagonists; increased risk of nephrotoxicity andpossibly hypermagnesaemia when ciclosporin given with thiazides and relatedDiuretics.Grapefruit Juice: plasma concentration of ciclosporin increased by .grapefruitjuice (increased risk of toxicity).Hormone Antagonists: metabolism of ciclosporin inhibited by danazol (increasedplasma concentration); plasma concentration of ciclosporin reduced by lanreotideand .octreotide.Lipid-regulating Drugs: increased risk of renal impairment when ciclosporingiven with bezafibrate or fenofibrate; increased risk of myopathy when ciclosporingiven with .rosuvastatin (avoid concomitant use); plasma concentration of bothdrugs may increase when ciclosporin given with .ezetimibe; increased risk ofmyopathy when ciclosporin given with .statins.Metoclopramide: plasma concentration of ciclosporin increased bymetoclopramide.Modafinil: plasma concentration of ciclosporin reduced by modafinil.Oestrogens: plasma concentration of ciclosporin possibly increased byoestrogens.Orlistat: absorption of ciclosporin possibly reduced by orlistat Potassium Salts:increased risk of hyperkalaemia when ciclosporin given with .potassium saltsProgestogens: metabolism of ciclosporin inhibited by progestogens (increasedplasma concentration).Sevelamer: plasma concentration of ciclosporin possibly reduced by sevelamerSirolimus: ciclosporin increases plasma concentration of sirolimus.Sitaxentan: ciclosporin increases plasma concentration of sitaxentan .Avoidconcomitant use.Sulfinpyrazone: plasma concentration of ciclosporin reduced by .sulfinpyrazoneTacrolimus: plasma concentration of ciclosporin increased by .tacrolimus(increased risk of nephrotoxicity). Avoid concomitant use.Ulcer-healing Drugs: plasma concentration of ciclosporin possibly increased bycimetidine; plasma concentration of ciclosporin possibly affected by omeprazole.38.CILOSTAZOLAnagrelide: avoidance of cilostazol advised by manufacturer of .anagrelide.Antibacterials: plasma concentration of cilostazol increased by .erythromycin(also plasma concentration of erythromycin reduced)—avoid concomitant use.Antifungals: plasma concentration of cilostazol possibly increased byketoconazole—avoid concomitant use.Antivirals: plasma concentration of cilostazol possibly increased byfosamprenavir, .indinavir, .lopinavir, nelfinavir, .ritonavir and .saquinavir—avoidconcomitant use.Calcium-channel Blockers: plasma concentration of cilostazol increased bydiltiazem—avoid concomitant use. 28
  29. 29. Ulcer-healing Drugs: plasma concentration of cilostazol possibly increased bycimetidine and lansoprazole—avoid concomitant use; plasma concentration ofcilostazol increased by .omeprazole (risk of toxicity)—avoid concomitant use.Muscle Relaxants: clindamycin enhances effects of non-depolarising musclerelaxants and .suxamethonium.39.CLONIDINEAntidepressants: enhanced hypotensive effect when clonidine given with MAOIs;hypotensive effect of clonidine antagonised by .tricyclics, also increased risk ofhypertension on clonidine withdrawal.Beta-blockers: increased risk of withdrawal hypertension when clonidine givenwith .beta-blockers (withdraw beta-blockers several days before slowlywithdrawing clonidine).Sympathomimetics: possible risk of hypertension when clonidine given withadrenaline (epinephrine) or noradrenaline (norepinephrine); serious adverseevents reported with concomitant use of clonidine and .methylphenidate (causalitynot established).40.CLOPIDOGRILAnticoagulants: manufacturer advises avoid concomitant use with warfarin;antiplatelet action of clopidogrel enhances anticoagulant effect of coumarins andphenindione; increased risk of bleeding when clopidogrel given with heparins.41.COLCHICINEAntibacterials: increased risk of colchicine toxicity when given withclarithromycin or .erythromycin.Ciclosporin: possible increased risk of nephrotoxicity and myotoxicity whencolchicine given with ciclosporin (increased plasma concentration of ciclosporin).Lipid-regulating Drugs: possible increased risk of myopathy when colchicinegiven with .statins.42.COLESTYRAMINEAnticoagulants: colestyramine may enhance or reduce anticoagulant effect ofcoumarins and phenindione.43.CORTICOSTEROIDSAntibacterials: plasma concentration of methylprednisolone possibly increased byclarithromycin; metabolism of corticosteroids possibly inhibited by erythromycin;metabolism of methylprednisolone inhibited by erythromycin; corticosteroidspossibly reduce plasma concentration of isoniazid; metabolism of corticosteroidsaccelerated by rifamycins (reduced effect).Anticoagulants: corticosteroids may enhance or reduce anticoagulant effect ofcoumarins (high-dose corticosteroids enhance anticoagulant effect). 29
  30. 30. Antiepileptics: metabolism of corticosteroids accelerated by .carbamazepine,phenytoin and .primidone (reduced effect).Antifungals: metabolism of corticosteroids possibly inhibited by itraconazole andketoconazole; plasma concentration of active metabolite of ciclesonide increasedby ketoconazole; plasma concentration of inhaled mometasone increased byketoconazole; plasma concentration of inhaled and oral budesonide increased byketoconazole; metabolism of methylprednisolone inhibited by ketoconazole;increased risk of hypokalaemia when corticosteroids given with amphotericin—avoid concomitant use unless corticosteroids needed to control reactions; plasmaconcentration of inhaled budesonide increased by itraconazole; metabolism ofmethylprednisolone possibly inhibited by itraconazole; dexamethasone possiblyreduces plasma concentration of caspofungin— consider increasing dose ofcaspofungin.Antivirals: dexamethasone possibly reduces plasma concentration of indinavir,lopinavir and saquinavir; plasma concentration of corticosteroids, dexamethasoneand prednisolone possibly increased by ritonavir; plasma concentration of inhaledandintranasal budesonide and fluticasone increased by ritonavir.Barbiturates: metabolism of corticosteroids accelerated by .barbiturates (reducedeffect).Ciclosporin: high-dose methylprednisolone increases plasma concentration of.ciclosporin (risk of convulsions); plasma concentration of prednisolone increasedby ciclosporin.Clonidine: corticosteroids antagonise hypotensive effect of clonidine.Cytotoxics: increased risk of haematological toxicity when corticosteroids givenwith .methotrexate.Diazoxide: corticosteroids antagonise hypotensive effect of diazoxide.Vaccines: high doses of corticosteroids impair immune response to .vaccines,avoid concomitant use with live vaccines.44.COUMARINSAlcohol: anticoagulant control with coumarins may be affected by major changesin consumption of alcohol.Anabolic Steroids: anticoagulant effect of coumarins nhanced by .anabolicsteroids.Analgesics: anticoagulant effect of coumarins possibly nhanced by .NSAIDs,celecoxib,dextropropoxyphene, .etodolac, .etoricoxib, flurbiprofen, .ibuprofen,mefenamic acid, meloxicam, .parecoxib, .piroxicam and .sulindac; anticoagulanteffect of coumarins enhanced by azapropazone (avoid concomitant use); anticoagulant effect of coumarins possibly enhanced by diclofenac, also increased risk ofhaemorrhage with intravenous diclofenac (avoid concomitant use); increased riskof bleeding when coumarins given with ketorolac (avoid concomitant use); anticoaguant effect of coumarins enhanced by .tramadol; increased risk of bleeding whencoumarins given with aspirin (due to antiplatelet effect); anticoagulant effect ofcoumarins possibly enhanced by prolonged regular use of paracetamol. 30
  31. 31. Anti-arrhythmics: metabolism of coumarins inhibited by amiodarone (enhancedanticoagulant effect); anticoagulant effect of coumarins enhanced by propafenoneAntibacterials: experience in anticoagulant clinics suggests that INR possiblyaltered when coumarins are given with .neomycin (given for local action ongut); anticoagulant effect of coumarins possibly enhanced by .azithromycin,.aztreonam,cephalosporins, levofloxacin, .tetracyclines, tigecycline andtrimethoprim; anticoagulant effect of coumarins enhanced by .chloramphenicol,ciprofloxacin, .clarithromycin, .erythromycin, metronidazole, .nalidixic acid,norfloxacin, ofloxacin and .sulphonamides; studies have failed to demonstrate aninteraction with coumarins, but common experience in anticoagulant clinics is thatINR can be altered by a course of broad-spectrum penicillins such as ampicillin;metabolism of coumarins accelerated by .rifamycins (reduced anticoagulant effect)Antidepressants: anticoagulant effect of warfarin possibly enhanced byvenlafaxine; anticoagulant effect of coumarins possibly enhanced by SSRIs;anticoagulant effect of coumarins reduced by .StJohn’s wort (avoid concomitantuse); anticoagulant effect of warfarin enhanced by mirtazapine; anticoagulanteffect of coumarins may be enhanced or reduced by .tricyclics.Antidiabetics: anticoagulant effect of warfarin possibly enhanced by exenatide;coumarins possibly enhance hypoglycaemic effect of .sulphonylureas, also possiblechanges to anticoagulant effect.Antiepileptics: metabolism of coumarins accelerated by .carbamazepine and.primidone (reduced anticoagulant effect); metabolism of coumarins acceleratedby .phenytoin (possibility of reduced anticoagulant effect, but enhancement alsoreported); anticoagulant effect of coumarins possibly enhanced by valproate.Antifungals: anticoagulant effect of coumarins enhanced by .fluconazole,itraconazole, ketoconazole and .voriconazole; anticoagulant effect of coumarinsenhanced by .miconazole (miconazole oral gel and possibly vaginal formulationsabsorbed); anticoagulant effect of coumarins reduced by .griseofulvin.Antimalarials: isolated reports that anticoagulant effect of warfarin may beenhanced by proguanil.Antivirals: anticoagulant effect of warfarin may be enhanced or reduced byatazanavir, .nevirapine and ritonavir; anticoagulant effect of coumarins may beenhanced or reduced by fosamprenavir; anticoagulant effect of coumarins possiblyenhanced by ritonavir; anticoagulant effect of warfarin possibly enhanced bysaquinavir.Anxiolytics and Hypnotics: anticoagulant effect of coumarins may transiently beenhanced by chloral and triclofosAprepitant: anticoagulant effect of warfarin possibly reduced by aprepitantBarbiturates: metabolism of coumarins accelerated by barbiturates (reducedanticoagulant effect).Bosentan: monitoring anticoagulant effect of coumarins recommended bymanufacturer of bosentan Clopidogrel: anticoagulant effect of coumarins enhanceddue to antiplatelet action of .clopidogrel; avoidance of warfarin advised bymanufacturer of clopidogrel. 31
  32. 32. Corticosteroids: anticoagulant effect of coumarins may be enhanced or reducedby .corticosteroids (highdose corticosteroids enhance anticoagulant effect)Cranberry Juice: anticoagulant effect of coumarins possibly enhanced by.cranberry juice—avoid concomitant use.Cytotoxics: anticoagulant effect of coumarins possibly enhanced by .etoposide,ifosfamide and .sorafenib; anticoagulant effect of coumarins enhanced byfluorouracil; anticoagulant effect of coumarins possibly reduced by .azathioprine,mercaptopurine and .mitotane; increased risk of bleeding when coumarins givenwith .erlotinib; replacement of warfarin with a heparin advised by manufacturer ofimatinib (possibility of enhanced warfarin effect).Dipyridamole: anticoagulant effect of coumarins enhanced due to antiplateletaction of .dipyridamole.Disulfiram: anticoagulant effect of coumarins enhanced by .disulfiram.Dopaminergics: anticoagulant effect of warfarin enhanced by .entacapone.Enteral Foods: anticoagulant effect of coumarins antagonised by vitamin K(present in some .enteral feeds ).Glucosamine: anticoagulant effect of warfarin enhanced by .glucosamine (avoidconcomitant use).Hormone Antagonists: anticoagulant effect of coumarins possibly enhanced bybicalutamide and toremifene; metabolism of coumarins inhibited by .danazol(enhanced anticoagulant effect); anti-coagulant effect of coumarins enhanced byflutamide and .tamoxifen.Levamisole: anticoagulant effect of warfarin possibly enhanced by .levamisoleLipid-regulating Drugs: anticoagulant effect of coumarinsmay be enhanced orreduced by.colestyramine; anticoagulant effect of warfarin may be transientlyreduced by atorvastatin; anticoagulant effect of coumarins enhanced by .fibrates,.fluvastatin and simvastatin; anticoagulant effect of coumarins possibly enhancedby ezetimibe and .rosuvastatin.Memantine: anticoagulant effect of warfarin possibly enhanced by memantineOestrogens: anticoagulant effect of coumarins may be enhanced or reduced byoestrogensOrlistat: monitoring anticoagulant effect of coumarins recommended bymanufacturer of orlistat.Progestogens: anticoagulant effect of coumarins may be enhanced or reduced byprogestogens.Raloxifene: anticoagulant effect of coumarins antagonized by raloxifene.Retinoids: anticoagulant effect of coumarins possibly reduced by .acitretin.Sibutramine: increased risk of bleeding when anticoagulants given withsibutramineSitaxentan: anticoagulant effect of coumarins enhanced by .sitaxentanSulfinpyrazone: anticoagulant effect of coumarins enhanced by .sulfinpyrazone.Sympathomimetics: anticoagulant effect of coumarins possibly enhanced by.methylphenidate 32
  33. 33. Terpene Mixture: anticoagulant effect of coumarins possibly reduced byRowachol.Testolactone: anticoagulant effect of coumarins enhanced by .testolactoneTestosterone: anticoagulant effect of coumarins enhanced by .testosteroneThyroid Hormones: anticoagulant effect of coumarins enhanced by .thyroidhormones.Ubidecarenone: anticoagulant effect of warfarin may be enhanced or reduced byubidecarenone.Ulcer-healing Drugs: metabolism of coumarins inhibited by .cimetidine(enhanced anticoagulant effect); anticoagulant effect of coumarins possiblyenhanced by esomeprazole, .omeprazole and pantoprazole; absorption ofcoumarins possibly reduced by sucralfate (reduced anticoagulant effect).Vaccines: anticoagulant effect of warfarin possibly enhanced by influenza vaccineVitamins: anticoagulant effect of coumarins antagonized by .vitamin K.45.CYCLOPHOSPHAMIDEAntipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).Cytotoxics: increased toxicity when high-dose cyclophosphamide given withpentostatin—avoid concomitant use.46.CYCLOSERINEAlcohol: increased risk of convulsions when cycloserine given with .alcohol.47.CYTARABINEAntipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).Analgesics: possible increased risk of bleeding when dabigatran etexilate givenwith .NSAIDs.Anti-arrhythmics: plasma concentration of dabigatran etexilate increased byamiodarone (reduce dose of dabigatran etexilate).48.DANAZOLAnticoagulants: danazol inhibits metabolism of coumarins (enhancedanticoagulant effect).Antiepileptics: danazol inhibits metabolism of carbamazepine(increased toxicity).Ciclosporin: danazol inhibits metabolism of ciclosporin (increased plasmaconcentration).Lipid-regulating Drugs: possible increased risk of myopathy when danazol givenwith .simvastatin.49.DAPTOMYCINCiclosporin: increased risk of myopathy when daptomycin given with .ciclosporin(preferably avoid concomitant use). 33
  34. 34. Lipid-regulating Drugs: increased risk of myopathy when daptomycin given withfibrates or .statins (preferably avoid concomitant use).50.DARUNAVIRAntibacterials: darunavir increases plasma concentration of .rifabutin (reducedose of rifabutin); plasma concentration of darunavir significantly reduced byrifampicin—avoid concomitant use.Antidepressants: darunavir possibly reduces plasma concentration of paroxetineand sertraline; plasma concentration of darunavir reduced by .St John’s wort—avoid concomitant use.Antivirals: plasma concentration of darunavir reduced by efavirenz andsaquinavir; plasma concentration of both drugs increased when darunavir givenwith indinavir; plasma concentration of darunavir reduced by .lopinavir, alsoplasma concentration of lopinavir increased (avoid concomitant use); darunavirincreases plasma concentration of .maraviroc (consider reducing dose ofmaraviroc).Lipid-regulating Drugs: darunavir possibly increases plasma concentration ofpravastatin; possible increased risk of myopathy when darunavir given with.rosuvastatin—avoid concomitant use.51.DASATINIBAntibacterials: metabolism of dasatinib accelerated by rifampicin (reducedplasma concentration—avoid concomitant use).Antipsychotics: avoid concomitant use of cytotoxics with .clozapine (increasedrisk of agranulocytosis).Cardiac Glycosides: cytotoxics reduce absorption of digoxin tablets.52.DIDANOSINEAllopurinol: plasma concentration of didanosine increased by .allopurinol (risk oftoxicity)—avoid concomitant use.Antivirals: plasma concentration of didanosine possibly increased by ganciclovir;increased risk of side-effects when didanosine given with .ribavirin—avoidconcomitant use; increased risk of side-effects when didanosine given withstavudine; plasma concentration of didanosine increased by .tenofovir (increasedrisk of toxicity)—avoid concomitant use;. plasma concentration of didanosinereduced by tipranavir.Cytotoxics: increased risk of toxicity when didanosine given with hydroxycarbamide—avoid concomitant use.53.DIMERCAPROLIron: avoid concomitant use of dimercaprol with .iron.54.DIMETHYL SULFOXIDEAnalgesics: avoid concomitant use of dimethyl sulfoxide with .sulindac. 34
  35. 35. 55.DIPYRIDAMOLEAnti-arrhythmics: dipyridamole enhances and extends he effects of .adenosine(important risk of toxicity).Anticoagulants: antiplatelet action of dipyridamole enhances anticoagulant effectof .coumarins and henindione; dipyridamole enhances anticoagulant effect ofheparins.56.DISOPYRAMIDEAnti-arrhythmics: increased myocardial depression when anti-arrhythmics givenwith other .antiarrhythmics; increased risk of ventricular arrhythmias whendisopyramide given with .amiodarone—avoid concomitant use.Antibacterials: plasma concentration of disopyramide possibly increased byclarithromycin (increased risk of toxicity); plasma concentration of disopyramideincreased by .erythromycin (increased risk of toxicity); increased risk ofventricular arrhythmias when disopyramide given with .moxifloxacin or.quinupristin/ dalfopristin—avoid concomitant use; metabolism of disopyramideaccelerated by .rifamycins (reduced plasma concentration)Antidepressants: increased risk of ventricular arrhythmias when disopyramidegiven with .tricyclics.Antifungals: increased risk of ventricular arrhythmias when disopyramide givenwith .ketoconazole—avoid concomitant use; avoidance of disopyramide advised bymanufacturer of .itraconazole.Antihistamines: increased risk of ventricular arrhythmias when disopyramidegiven with .mizolastine— avoid concomitant use.Antimalarials: avoidance of disopyramide advised by manufacturerofartemether /lumefantrine (risk of ventricular arrhythmias).Antimuscarinics: increased risk of antimuscarinic sideeffects when disopyramidegiven with antimuscarinics; increased risk of ventricular arrhythmias whendisopyramide given with .tolterodine.Antipsychotics: increased risk of ventricular arrhythmias when anti-arrhythmicsthat prolong the QT interval given with .antipsychotics that prolong the QTinterval; increased risk of ventricular arrhythmias when disopyramide given withamisulpride, .pimozide, .sertindole or zuclopenthixol—avoid concomitant use;increased risk of ventricular arrhythmias when disopyramide given withphenothiazines or sulpiride.Antivirals: plasma concentration of disopyramide possibly increased by .ritonavir(increased risk of toxicity).Atomoxetine: increased risk of ventricular arrhythmias when disopyramide givenwith .atomoxetine.Beta-blockers: increased myocardial depression when anti-arrhythmics givenwith .beta-blockers; increased risk of ventricular arrhythmias when disopyramidegiven with .sotalol—avoid concomitant use.Calcium-channel Blockers: increased risk of myocardial depression and asystolewhen disopyramide given with .verapamil. 35
  36. 36. Diuretics: increased cardiac toxicity with disopyramide if hypokalaemia occurswith .acetazolamide, .loop diuretics or .thiazides and related diuretics.5HT Antagonists: increased risk of ventricular arrhythmias when disopyramidegiven with .dolasetron— avoid concomitant use.Ivabradine: increased risk of ventricular arrhythmias when disopyramide givenwith .ivabradine.57.DISULFIRAMAnticoagulants: disulfiram enhances anticoagulant effect of .coumarins.Antiepileptics: disulfiram inhibits metabolism of phenytoin (increased risk oftoxicity).Paraldehyde: risk of toxicity when disulfiram given with .paraldehyde.58.DIURETICSACE Inhibitors: enhanced hypotensive effect when diuretics given with .ACEinhibitors; increased risk of severe hyperkalaemia when potassium-sparingdiuretics and aldosterone antagonists given with .ACE inhibitors (monitorpotassium concentration with low-dose spironolactone in heart failure).Alpha-blockers: enhanced hypotensive effect when diuretics given with .alpha-blockers, also increased risk of first-dose hypotension with post-synaptic alpha-blockers such as prazosin.Analgesics: Diuretic effect of potassium canrenoate possibly antagonised byNSAIDs; possibly increased risk of hyperkalaemia when potassium-sparingdiuretics and aldosterone antagonists given with NSAIDs; diuretics increase risk ofnephrotoxicity of NSAIDs, also antagonism of diuretic effect; effects of diureticsantagonised by indometacin and ketorolac; increased risk of hyperkalaemia whenpotassium-sparing diureticsand aldosterone antagonists given with indometacin;occasional reports of reduced renal function when triamterene given with.indometacin—avoid concomitant use; increased risk of toxicity when carbonicanhydrase inhibitors given with high-dose aspirin; diuretic effect of spironolactoneantagonisedby aspirin. Angiotensin-II Receptor Antagonists: enhanced hypotensiveeffect when diuretics given with angiotensin-II receptor antagonists; increased riskof hyperkalaemia when potassium-sparing diuretics and aldosterone antagonistsgiven with .angiotensin-II receptor antagonists.Anti-arrhythmics: plasma concentration of eplerenone increased by amiodarone(reduce dose of eplerenone); hypokalaemia caused by acetazolamide, loopdiuretics or thiazides and related diuretics increases cardiac toxicity withamiodarone; hypokalaemia caused by acetazolamide, loop diuretics or thiazidesand related diuretics increases cardiac toxicity with disopyramide; hypokalaemiacaused by acetazolamide, loop diuretics or thiazides and related diuretics increasescardiac toxicity with .flecainide; hypokalaemia caused by acetazolamide, loopdiuretics or thiazides and related diuretics antagonizes action of .lidocaine(lignocaine) 36

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