Terfenadine Carbamazepine

CYP3A4 Amiodarone, terfenadine Carbamazepine, phenytoin Erythromycin, grapefruit juice,... 

CYP3A4 alprazolam, calcium channel blockers, cisapride, clarithromycin, cyclosporin A, erythromycin, HIV protease inhibitors, lidocaine, midazolam, simvastatin, terfenadine carbamazepine, dexamethsone, phenobarbital, phenytoin, rifampicin, St John s wort cimetidine, erythromycin, grapefruit juice, HIV protease inhibitors, itraconazole, ketoconazole... 

CYP3A4 is highly inducible by a large variety of commonly prescribed and utilized synthetic drugs (e.g., carbamazepine) and plant products (e.g., St. John s wort) (Roby, Anderson et al, 2000), and at the same time also is potently inhibited by various other medications (e.g., terfenadine and ketoconazole) (Jurima-Romet, Crawford etal, 1994) as well as common foodstuffs (e.g., grapefruit juice) (Oesterheld 8c Kallepalli, 1997). Since individual and ethnic/cultural groups vary dramatically in their exposure to these inducers and inhibitors, it stands to reason that... 

Codeine, dextromethorphan, haloperidol, thioridazine, perphenazine, nortriptyline, desipramine, fluoxetine, norfluoxetine, TCAs (hydroxylation), beta-blockers such as timolol and metoprolol, type 1C antiarrhythmics encainide, flecainide TCAs (desmethylation), triazolam, alprazolam, midazolam, carbamazepine, terfenadine, quinidine, lidocaine, erythromycin, cyclosporin... 

Contraindications Co-administration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine hypersensitivity to other phenylpiperazine antidepressants those who were withdrawn from nefazodone due to evidence of hepatic injury use within 14 days of MAOIs... 

All SSRIs (e.g., Feonard et ah, 1997) and in particular fluoxetine, Fluvosamine and paroxetine are metabolized by hepatic cytochrome P450 enzymes. Therefore, it is important to be aware of the possibility that the therapeutic or toxic effects of other medications metabolized by the cytochrome P450 isoenzyme system can be increased. Substantial inhibition of these isoenzymes converts a normal metabolizer into a slow metabolizer with regard to this specific pathway. Inhibition of the hepatic oxidative isoenzymes has been associated with a reduction, to a varying extent, in the clearance of many therapeutic agents, including the TCAs, several neuroleptics, antiarrhythmics, theophy-lene, terfenadine, benzodiazepines, carbamazepine, and warfarin (for a complete list, see Nemeroff et ak, 1996). 

Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include cimetidine, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, nefazodone, loratadine, terfenadine, isoniazid, niacinamide, nicotinamide, propoxyphene, azoles (e.g., ketaconazole, itraconazole, and fluconazole), acetazolamide, verapamil, grapefruit juice, ... 

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... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

Interactions Erythromycin and clarithromycin inhibit the hepatic metabolism of theophylline, warfarin, terfenadine, astemizole, carbamazepine and cyclosporine which can lead to toxic accumulations of these drugs. An interaction with digoxin may occur in some patients. In this case, the antibiotic eliminates a species of intestinal flora that ordinarily inactivates digoxin, thus leading to greater reabsorption of digoxin from the enterohepatic circulation. 

Nefazodone is a weak inhibitor of CYP2D6 but a potent inhibitor of CYP3A4 and it increases plasma concentrations of drugs that are substrates of CYP3A4, such as alprazolam, astemizole, carbamazepine, ciclosporin, cisapride, terfenadine, and triazolam. 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with amiodarone, astemizole, bepridil, carbamazepine, chloroquine, cisapride, clarithromycin, dihydroergotamine, disopyramide, ergotamine, grapefruit juice, halofantrine, haloperidol, itraconazole, ketoconazole, methadone, moxifloxacin, phenobarbital, phenytoin, pimozide, procainamide, quinidine, rifampicin, ritonavir, sotalol, St John s wort, telithromycin, terfenadine, voriconazole... 

Figure 2.7 Plot of aqueous solubility using amorphous versus crystalline material at pH 7.4 following 24 h agitation. (1) Disulfiram, (2) astemizole, (3) bicalutamide, (4) ketoconazole, (5) loperamide, (6) glyburide, (7) griseofulvin, (8) terfenadine, (9) nifedipine, (10) haloperidol, (11) testosterone, (12) flutamide, (13) bitolterol, (14) diazepam, (15) carbamazepine, (16) chlorzoxazone.

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

One of the important limitations to the widespread use of the macrolides has been the propensity to interact with other commonly administered medications. Serious, sometimes life-threatening, consequences have resulted from the administration of macrolides to patients receiving routine medications including theophylline, carbamazepine, terfenadine, and other frequently prescribed medications [4-6]. Most of these interactions involve inhibition of drug metabolism via cytochrome P-450 microsomal enzyme. However, not all macrolides have been associated with such drug interactions. 

Azithromycin Early evidence suggests that azithromycin does not inhibit hepatic drug metabolism. It does not appear to interact with carbamazepine, theophylline, or terfenadine. 

Clarithromycin Appears to act as an inhibitor of hepatic metabolism, but relative potency compared with erythromycin is not clear it appears to inhibit the metabolism of theophylline, carbamazepine, and terfenadine. 

Studies of the concomitant use of azithromycin with carbamazepine, terfenadine, and zidovudine have not reported drug interactions [131-133]. With the potential exception of antacids, no drug interactions have been reported with azithromycin, which does not appear to be metabolized by the cytochrome P-450 system [4, 134], Both azithromycin and clarithromycin have been associated with digoxin toxicity. The postulated mechanism is by eradication of Eubacterium lentum, an anaerobic gram-positive bacteria responsible for the metabolism of digoxin in some patients [43]. 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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