BNF for Children 2011-2012

BNFC 2011–2012 Appendix 1: Interactions 719Phenobarbital. Calcium-channel Blockers (continued)manufacturer of .nimodipine (plasma concentrationof nimodipine reduced). Ciclosporin: phenobarbital accelerates metabolism of.ciclosporin (reduced plasma concentration). Corticosteroids: phenobarbital accelerates metabolismof .corticosteroids (reduced effect)Cytotoxics: avoidance of phenobarbital advised bymanufacturer of gefitinib; phenobarbital possiblyreduces plasma concentration of etoposide; phenobarbitalreduces plasma concentration of irinotecanand its active metabolite. Diuretics: phenobarbital reduces plasma concentrationof .eplerenone—avoid concomitant use; increasedrisk of osteomalacia when phenobarbital given withcarbonic anhydrase inhibitorsFolates: plasma concentration of phenobarbital possiblyreduced by folatesHormone Antagonists: phenobarbital acceleratesmetabolism of toremifene (reduced plasma concentration)Leukotriene Receptor Antagonists: phenobarbitalreduces plasma concentration of montelukast. Oestrogens: phenobarbital accelerates metabolism of.oestrogens (reduced contraceptive effect—seep. 398). Orlistat: possible increased risk of convulsions whenantiepileptics given with .orlistat. Progestogens: phenobarbital accelerates metabolismof .progestogens (reduced contraceptive effect—seep. 398)Sodium Oxybate: avoidance of phenobarbital advisedby manufacturer of sodium oxybateSympathomimetics: plasma concentration of phenobarbitalpossibly increased by methylphenidate. Tacrolimus: phenobarbital reduces plasma concentrationof .tacrolimus. Theophylline: phenobarbital accelerates metabolism of.theophylline (reduced effect)Thyroid Hormones: phenobarbital accelerates metabolismof thyroid hormones (may increase requirementsfor thyroid hormones in hypothyroidism). Ulipristal: avoidance of phenobarbital advised bymanufacturer of .ulipristal (contraceptive effect ofulipristal possibly reduced)Vitamins: phenobarbital possibly increases requirementsfor vitamin DPhenothiazines see AntipsychoticsPhenoxybenzamine see Alpha-blockersPhenoxymethylpenicillin see PenicillinsPhentolamine see Alpha-blockersPhenylephrine see SympathomimeticsPhenytoinNote Fosphenytoin interactions as for phenytoinAlcohol: plasma concentration of phenytoin possiblyreduced by chronic heavy consumption of alcoholAnalgesics: phenytoin accelerates metabolism ofmethadone (reduced effect and risk of withdrawaleffects); effects of phenytoin enhanced by aspirinAntacids: absorption of phenytoin reduced by antacids. Anti-arrhythmics: metabolism of phenytoin inhibitedby .amiodarone (increased plasma concentration);phenytoin reduces plasma concentration of disopyramide;phenytoin possibly reduces plasma concentrationof .dronedarone—avoid concomitant use. Antibacterials: metabolism of phenytoin inhibited byclarithromycin (increased plasma concentration);metabolism of phenytoin possibly inhibited bymetronidazole (increased plasma concentration);plasma concentration of phenytoin increased ordecreased by ciprofloxacin; phenytoin acceleratesmetabolism of doxycycline (reduced plasma concentration);plasma concentration of phenytoinincreased by .chloramphenicol (increased risk oftoxicity); metabolism of phenytoin possibly inhibitedby isoniazid (increased risk of toxicity); metabolism ofphenytoin accelerated by .rifamycins (reducedPhenytoin. Antibacterials (continued)plasma concentration); plasma concentration ofphenytoin possibly increased by sulfonamides;phenytoin reduces plasma concentration of.telithromycin (avoid during and for 2 weeks afterphenytoin); plasma concentration of phenytoinincreased by .trimethoprim (also increased antifolateeffect). Anticoagulants: phenytoin accelerates metabolism of.coumarins (possibility of reduced anticoagulanteffect, but enhancement also reported). Antidepressants: plasma concentration of phenytoinincreased by .fluoxetine and .fluvoxamine; phenytoinreduces plasma concentration of .mianserin,mirtazapine and paroxetine; plasma concentration ofphenytoin possibly increased by sertraline, alsoplasma concentration of sertraline possibly reduced;anticonvulsant effect of antiepileptics possiblyantagonised by MAOIs and .tricyclic-related antidepressants(convulsive threshold lowered); anticonvulsanteffect of antiepileptics antagonised by.SSRIs and .tricyclics (convulsive thresholdlowered); avoid concomitant use of antiepilepticswith .St John’s wort; phenytoin possibly reducesplasma concentration of .tricyclicsAntidiabetics: plasma concentration of phenytointransiently increased by tolbutamide (possibility oftoxicity). Antiepileptics: plasma concentration of both drugsoften reduced when phenytoin given with carbamazepine,also plasma concentration of phenytoinmay be increased; phenytoin reduces plasma concentrationof eslicarbazepine, also plasma concentrationof phenytoin increased; plasma concentrationof phenytoin possibly increased by .ethosuximide,also plasma concentration of ethosuximide possiblyreduced; phenytoin reduces plasma concentration oflamotrigine, tiagabine and zonisamide; plasma concentrationof phenytoin increased by oxcarbazepine,also plasma concentration of an active metabolite ofoxcarbazepine reduced; phenytoin often increasesplasma concentration of phenobarbital, plasma concentrationof phenytoin often reduced but may beincreased; phenytoin possibly reduces plasma concentrationof rufinamide, also plasma concentrationof phenytoin possibly increased; plasma concentrationof phenytoin increased by .stiripentol; plasmaconcentration of phenytoin increased by .topiramate(also plasma concentration of topiramate reduced);plasma concentration of phenytoin increased orpossibly reduced when given with valproate, alsoplasma concentration of valproate reduced; plasmaconcentration of phenytoin reduced by vigabatrin. Antifungals: phenytoin reduces plasma concentrationof .ketoconazole and .posaconazole; anticonvulsanteffect of phenytoin enhanced by .miconazole(plasma concentration of phenytoin increased);plasma concentration of phenytoin increased by.fluconazole (consider reducing dose of phenytoin);phenytoin reduces plasma concentration of.itraconazole—avoid concomitant use; plasma concentrationof phenytoin increased by .voriconazole,also phenytoin reduces plasma concentration ofvoriconazole (increase dose of voriconazole and alsomonitor for phenytoin toxicity); phenytoin possiblyreduces plasma concentration of caspofungin—considerincreasing dose of caspofungin. Antimalarials: possible increased risk of convulsionswhen antiepileptics given with chloroquine andhydroxychloroquine; anticonvulsant effect of antiepilepticsantagonised by .mefloquine; anticonvulsanteffect of phenytoin antagonised by.pyrimethamine, also increased antifolate effect. Antipsychotics: anticonvulsant effect of antiepilepticsantagonised by .antipsychotics (convulsive thresholdlowered); phenytoin reduces plasma concentration ofhaloperidol; plasma concentration of phenytoinAppendix 1: Interactions