Phenytoin Disulfiram

Phenytoin serum levels are markedly and rapidly increased by disulfiram. Phenytoin toxicity can develop. There is evidence that phenobarbital and carbamazepine are not affected by disulfiram, and that phenytoin is not affected by calcium carbimide. 

Disulfiram decreases the metabolism of phenytoin, resulting in higher phenytoin levels the dose of phenytoin will need to be reduced since phenytoin undergoes nonlinear metabolism it is difficult to predict the magnitude of increase in blood levels that could be seen it is best to avoid this interaction if possible otherwise, closely monitor phenytoin blood levels. 

Sulthiame (H7, 04), phcnacoraidc (H15), chloramphenicol (C5),dicou-marol (H6), antituberculous drugs (K23), disulfiram and phenyramidol (S23) have been described as inhibitors of phenytoin metabolism, while alcohol and possibly phenobarbitone have the reverse effect. Clinical and experimental evidence regarding the latter are confusing (B16, B29, C11,C12). 

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Flurazepam (Dalmane) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose Adults Beds >15 y. 15-30 mg PO qhs PRN X in elderly Caution [X, /-] Elderly, low albumin, hepatic impair Contra NAG PRG Disp Caps SE Hangover d/t accumulation of metabolites, apnea, anaphylaxis, angioedema, amnesia Interactions T CNS depression W/ antidepressants, antihistamines, opioids, EtOH T effects OF digoxin, phenytoin T effects W/ cimetidine, disulfiram, fluoxetine, iso-niazid, ketoconazole, metoprolol, OCPs, propranolol, SSRIs, valproic acid. 

Interferes w/ DNA synth Dose Adults. Anaerobic Infxns 500 mg IV q6-8h Amebic dysentery 750 mg/d PO for 5-10 d Trichomoniasis 250 mg PO tid for 7 d or 2 g PO X 1 C. difficile 500 mg PO or IV qSh for 7-10 d (PO preferred IV only if pt NPO) Vaginosis 1 applicator-full intravag bid or 500 mg PO bid for 7 d Acne rosacea/skin Apply bid Peds. 30 mg/ kg PO/IV/d q6H, 4 g/d max-s-. Amebic dysentery 35-50 mg/kg/24 h PO in 3 -s- doses for 5-10 d Rx 7-10 d for C. difficile-, in hepatic impair Caution [B, M] Avoid EtOH Contra 1st tri of PRO Disp Tabs, caps, IV, topical lotion, intravag gel, cream SE Disulfiram-like Rxn dizziness, HA, GI upset, anorexia, urine discoloration Interactions t Effects W/ cimetidine T effects OF carbamazepine, fluorouracil, Li, warfarin -1- effects W/ barbiturates, cholestyramine, colestipol, phenytoin EMS t Effects of anticoagulants concurrent EtOH use can cause disulfiram-like Rxn (tach, N/V, sweating, flushing, headache, blurred vision, confusion) may cause a metallic taste and discolored urine OD May cause N/V/D, numbness in hands and feet, Szs, and loss of coordination symptomatic and supportive... 

Phenytoin (Dilantin) [Anticenvulsant/Hydantoin] Uses Sz disorders Action X Sz spread in the motor cortex Dose Load Adults Peds. 15-20 mg/kg IV, 25 mg/min max or PO in 400-mg doses at 4-h intervals Maint Adults. Initial, 200 mg PO or IV bid or 300 mg hs then follow levels Peds. 4-7 mg/kg/24h PO or IV -s- daily-bid avoid PO susp (erratic absorption) Caution [D, +] Contra Heart block, sinus bradycardia Disp Caps, susp, inj SE Nystag-mus/ataxia early signs of tox gum hyperplasia w/ long-term use. IV BP, bradycardia, arrhythmias, phlebitis peripheral neuropathy, rash, blood dyscrasias, Stevens-Johnson synd Notes Levels Trough Just before next dose Therapeutic Peak 10-20 mcg/mL Toxic >20 mcg/mL phenytoin albumin bound, levels = bound free phenytoin w/ i albumin azotemia, low levels may be therapeutic (nl free levels) Interactions T Effects W/ amiodarone, allopurinol, chloramphenicol, disulfiram, INH, omeprazole, sulfonamides, quinolones, trimethoprim t... 

Quazepam (Doral) [C IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose 7.5-15 mg PO hs PRN i in elderly hqjatic failure Caution [X, /-] NA glaucoma Contra PRG, sleep apnea Disp Tabs SE Sedation, hangovCT, somnolence, resp depression Interactions T Effects W/ azole antifungals, cimetidine, digoxin, disulfiram, INH, levodopa, macrolides, neuroleptics, phenytoin, quinolones, SSRIs, verapamil, grapefruit juice, EtOH effects W/carbamazepine, rifampin, rifabutin, tobacco EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH and grapefruit juice use T CNS depression OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote activated charcoal may be effective... 

Plasma phenytoin concentrations are increased in the presence of chloramphenicol, disulfiram, and isoniazid, since the latter drugs inhibit the hepatic metabolism of phenytoin. A reduction in phenytoin dose can alleviate the consequences of these drug-drug interactions. 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

Primidone Disulfiram Dextroamphetamine Valproic acid Phenylephrine Phenytoin Isoetharine Carbamazepine Amitriptyline Triazolam Diazepam... 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Disulfiram is rapidly and completely absorbed from the gastrointestinal tract however, a period of 12 hours is required for its full action. Its elimination rate is slow, so that its action may persist for several days after the last dose. The drug inhibits the metabolism of many other therapeutic agents, including phenytoin, oral anticoagulants, and isoniazid. It... 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

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