Terfenadine Amiodarone

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

Citrus flavinoids in grapefruit (but not orange) juice decrease hepatic metaboUsm and may lead to risk of toxicity from amiodarone, terfenadine (cardiac arrhythmia), benzodiazepines (increased sedation), ciclosporin, felodipine (reduced blood pressure). 

Ruelle, J. A., Tsinman, 0., Avdeef, A. Acid-base cosolvent method for determining aqueous permeability of amiodarone, itraconazole, tamoxifen, terfenadine and other very insoluble molecules. Chem. Pharm. Bull. 2004, 52, 551-555. 

The enzyme is the principal participant in N-demethylation reactions where the substrate is a tertiary amine. The list of substrates includes erythromycin, ethylmor-phine, lidocaine, diltiazem, tamoxifen, toremifene, verapamil, cocaine, amiodarone, alfentanil and terfenadine. Carbon atoms in the allylic and benzylic positions, such as those present in quinidine, steroids and cyclosporin A, are also particularly prone to oxidation by CYP3A4, a range of substrates is illustrated in Figure 7.10. 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Amiodarone, sotalol, quinidine, disopyramide Terfenadine, astemizole... 

Contraindications Concurrent use of amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, encainide, flecainide, meperidine, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, or terfenadine (increased risk of serious or life-... 

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 ... 

The pharmacokinetics of saquinavir is modified by agents that alter isoenzyme CYP3A4 of the cytochrome P-450 system and P-glycoprotein transporter. It should not be administered with midazolam, triazolam and ergot derivatives. The plasma concentrations of saquinavir are lower when coadministered with efavirenz, nevirapine or rifampin. Ritonavir reverses the effects of nevirapine on saquinavir. The coadministration of astemizole, terfenadine, amiodarone, bepridil, quinidine, propafenone or flecainide with saquinavir is also not recommended due to its potential for serious and/or life-threatening reactions. 

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... 

VENLAFAXINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS-TCAs 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemetherwith lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS -sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

Mibefradil inhibits CYP3A4 (2). Other drugs that are metabolized by this pathway accumulate as a result. Drugs that were commonly affected included amiodarone, astemizole, ciclosporin, cisapride, erythromycin, imi-pramine, lovastatin, propafenone, quinidine, simvastatin (9), tacrohmus (10), tamoxifen, terfenadine, thioridazine, and drugs that impair sinoatrial node function (for example beta-blockers) (6). 

Benzodiazepines alprazolam, clonazepam, diazepam, midazolam, triazolam, zolpidem Calcium channel blockers diltiazem, nifedipine, nimodipine, verapamil Steroids androgens, estrogens, cortisol Others erythromycin, terfenadine, cyclosporine, dapsone, ketoconazole, lovastatin, lidocaine, alfentanil, amiodarone, astemizole, codeine, sildenafil... 

Clinically important, potentially hazardous interactions with amiodarone, bepridil, cisapride, disopyramide, droperidol, erythromycin, flecainide, levodopa, pentamidine, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine... 

Clinically important, potentially hazardous interactions with amiodarone, azithromycin, bepredil, bosentan, bretylium, cisapride, clarithromycin, disopyramide, erythromycin, erythromycin fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nefazodone, nilotinib, paroxetine, pimozide, probucol, procainamide, quinidine, quinine, ritonavir, saquinavir, sertraline, sotalol, SSRIs, terfenadine, troleandomycin, voriconazole, zileuton, ziprasidone... 

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... 

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