Iron Supplements and Foods Fortified With Iron Concomitant administration of cefdinir with a therapeutic iron supplement containing 60 mg of elemental iron (as FeSO4) or vitamins supplemented with 10 mg of elemental iron reduced extent of absorption by 80% and 31%, respectively.


Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;


Patients who begin taking diclofenac or who increase their diclofenac dose or any other NSAID while taking digoxin, methotrexate, or cyclosporine may develop toxicity characteristics for these drugs.


Antacids: Concomitant administration of antacids may reduce plasma levels of diflunisal.


Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as NIMBEX include certain antibiotics (e. g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistemethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine.


Because of reports of prolongation of the prothrombin time beyond the therapeutic range in patients taking concurrent levamisole and warfarin sodium, it is suggested that the prothrombin time be monitored carefully, and the dose of warfarin sodium or other coumarin-like drugs should be adjusted accordingly, in patients taking both drugs.


The half-life of ketamine in plasma and brain was longer in the presence of halothane than when ketamine was given alone.


Drugs that cause significant sustained elevation in gastric pH (histamine H2-receptor antagonists such as ranitidine or cimetidine) may reduce plasma concentrations of IRESSA and therefore potentially may reduce efficacy.


Based on these data, Vardenafil should not be used in patients on alpha-blocker therapy.


Compounds tested in man include warfarin, theophylline, phenytoin, diazepam, aminopyrine and antipyrine.


Therefore, co-administration of bupropion with drugs that are metabolized by CYP2D6 isoenzyme including certain antidepressants (e.g., nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication.


The most commonly occurring drug interactions are listed below: - Drugs that may increase plasma phenytoin concentrations include: acute alcohol intake, amiodarone, chboramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone


Benzodiazepines: Combination hormonal contraceptives may decrease the clearance of some benzodiazepines (alprazolam, chlordiazepoxide, diazepam) and increase the clearance of others (lorazepam, oxazepam, temazepam).


Additionally, anti-malarial drugs, such as chloroquine and mefloquine, may antagonize the activity of carbamazepine.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


Binding to Serum Proteins: The following agents may either inhibit levothyroxine sodium binding to serum proteins or alter the concentrations of serum binding proteins: androgens and related anabolic hormones, asparaginase, clofibrate, estrogens and estrogen-containing compounds, 5-fluorouracil, furosemide, glucocorticoids, meclofenamic acid, mefenamic acid, methadone, perphenazine, phenylbutazone, phenytoin, salicylates, tamoxifen.


The administration of guanfacine concomitantly with known microsomal enzyme inducer (phenobarbital or phenytoin) to two patients with renal impairment reportedly resulted in significant reductions in elimination half-life and plasma concentration.


Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists.


Anticonvulsants (carbamazepine, felbamate, phenobarbital, phenytoin, topiramate): Increase the metabolism of ethinyl estradiol and/or some progestins, leading to possible decrease in contraceptive effectiveness.


When other potent parental antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure.


The concomitant use of H2 blockers or proton pump inhibitors with SPRYCEL is not recommended.


These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.


Protein Binding In vitro, diclofenac interferes minimally or not at all with the protein binding of salicylic acid (20% decrease in binding), tolbutamide, prednisolone (10% decrease in binding), or warfarin.


As with most psychoactive medications, patients should be advised to avoid alcohol while taking ABILIFY


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


Magnesium- and/or aluminum-containing antacids, products containing ferrous sulfate (iron), multivitamin preparations containing zinc or other metal cations, or Videx (didanosine) chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 3 hours before or 2 hours after FACTIVE.


Intraventricular injection of naloxone at doses of 1.2 to 12 micrograms equally antagonized in a dose-dependent manner the tail-flick inhibition induced by intraventricular beta-endorphin and morphine.


Because eprosartan is not metabolized by the cytochrome P450 system, inhibitors of CYP450 enzyme would not be expected to affect its metabolism, and ketoconazole and fluconazole, potent inhibitors of CYP3A and 2C9, respectively, have been shown to have no effect on eprosartan pharmacokinetics.


Antacids: In a clinical pharmacology study, coadministration of an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril administered alone, suggesting that antacids may impair absorption of fosinopril.


A clinical study in healthy male volunteers (n=24) demonstrated that mixing NovoLog with NPH human insulin immediately before injection produced some attenuation in the peak concentration of NovoLog, but that the time to peak and the total bioavailability of NovoLog were not significantly affected.


ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors.


Particular caution should be observed with digitalis preparations since there are conflicting results for the effect of colestipol hydrochloride on the availability of digoxin and digitoxin.


The availability of potent non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens for antiretroviral therapy and concerns regarding protease inhibitor (PI)-related metabolic disturbances have led to significant shifts in treatment practices in HIV infection.


A direct causal relationship has not been established, but physicians should consider the possibility that diclofenac may alter a diabetic patient s response to insulin or oral hypoglycemic agents.


Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;


Lithium: Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


Patients who are applying Panretin gel should not concurrently use products that contain DEET (N, N-diethyl-m-toluamide), a common component of insect repellent products.


Although beta-adrenergic blockers or calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block.


The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved.


Digitalis: Immediate Release Capsules: Since there have been isolated reports of patients with elevated digoxin levels, and there is a possible interaction between digoxin and nifedipine, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing nifedipine to avoid possible over- or under-digitalization.


Administration of quinolones with antacids containing aluminum, magnesium, or calcium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as VIDEX (didanosine) chewable/buffered tablets or the pediatric powder for oral solution, may substantially interfere with the absorption of quinolones, resulting in systemic concentrations considerably lower than desired.


acetaminophen/theophylline, lidocaine/quinidine, phenobarbital/acetaminophen, phenobarbital/valproic acid, quinidine/lidocaine, theophylline/acetaminophen, and valproic acid/phenobarbital.


Fluoxetine, OCs, sertraline, diltiazem, macrolide antibiotics (exercise caution).


The benefits and risks of using TRICOR with immunosuppressants and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed


Carbamazepine: Carbamazepine causes an approximate 50% increase in the clearance of Felbatol  at steady state and, therefore, the addition of carbamazepine results in an approximate 40% decrease in the steady-state trough concentrations of Felbatol  as compared to the same dose of Felbatol  given as monotherapy.


High-dose cyclosporin A resulting in concentrations above 2000 ng/mL administered with oral etoposide has led to an 80% increase in etoposide exposure with a 38% decrease in total body clearance of etoposide compared to etoposide alone.


Barbiturates may decrease the effectiveness of oral contraceptives, certain antibiotics, quinidine, theophylline, corticosteroids, anticoagulants, and beta blockers.


The results raise the possibility that the ethanolysis reaction may occur in the stomach of people who consume alcohol and 3-hydroxy-1,4-benzodiazepine on a regular basis.


Drugs that reduce the number of blood platelets by causing bone marrow depression (such as antineoplastic agents) or drugs which inhibit platelet function (eg, aspirin and other non-steroidal anti-inflammatory drugs, dipyridamole, hydrochloroquine, clofibrate, dextran) may increase the bleeding tendency produced by anticoagulants without altering prothrombin time determinations.


If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


This appears to be the only clinically relevant interaction of this kind with Mefloquine, although theoretically, coadministration of other drugs known to alter cardiac conduction (eg, anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H1-blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval.


Probenecid : Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine).


Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result.


Patients on warfarin-type anticoagulant therapy may require dosage adjustment of the anticoagulant during and after griseofulvin therapy.


In patients given very high doses (3900 mg) of aspirin daily, increases in serum salicylate levels were seen when nizatidine, 150 mg b.i.d., was administered concurrently.


In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78 weeks has been reported to cause tumors, and it has been suggested that disulfiram may react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic.


- Indomethacin: Indomethacin blunts the increases in urine volume and sodium excretion seen during bumetanide treatment and inhibits the bumetanide-induced increase in plasma renin activity.


Thyroid Physiology: The following agents may alter thyroid hormone or TSH levels, generally by effects on thyroid hormone synthesis, secretion, distribution, metabolism, hormone action, or elimination, or altered TSH secretion: aminoglutethimide, p-aminosalicylic acid, amiodarone, androgens and related anabolic hormones, complex anions (thiocyanate, perchlorate, pertechnetate), antithyroid drugs, b-adrenergic blocking agents, carbamazepine, chloral hydrate, diazepam, dopamine and dopamine agonists, ethionamide, glucocorticoids, heparin, hepatic enzyme inducers, insulin, iodinated cholestographic agents, iodine-containing compounds, levodopa, lovastatin, lithium, 6-mercaptopurine, metoclopramide, mitotane, nitroprusside, phenobarbital, phenytoin, resorcinol, rifampin, somatostatin analogs, sulfonamides, sulfonylureas, thiazide diuretics.


Agents that are CYP3A4 inhibitors that have been found, or are expected, to increase plasma levels of EQUETROTM are the following: Acetazolamide, azole antifungals, cimetidine, clarithromycin(1), dalfopristin, danazol, delavirdine, diltiazem, erythromycin(1), fluoxetine, fluvoxamine, grapefruit juice, isoniazid, itraconazole, ketoconazole, loratadine, nefazodone, niacinamide, nicotinamide, protease inhibitors, propoxyphene, quinine, quinupristin, troleandomycin, valproate(1), verapamil, zileuton.


Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as NUROMAX include certain antibiotics (e. g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistimethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine.


These results suggest that both dexamethasone and retinyl acetate, and possibly other glucocorticoids and retinoids, may regulate the proliferation of prostate epithelium by a dose-dependent modification of the activity of insulin and EGF.


Other Drugs: Based on the results of drug interaction studies, no dosage adjustment is recommended when SUSTIVA (efavirenz) is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lamivudine, lorazepam, nelfinavir, paroxetine, and zidovudine.


Valdecoxib caused a statistically significant increase in plasma exposures of R-warfarin and S-warfarin (12% and 15%, respectively), and in the pharmacodynamic effects (prothrombin time, measured as INR) of warfarin.


Antiepileptic Drugs: Sporadic cases of seizures have been reported during concomitant use of TORADOL and antiepileptic drugs (phenytoin, carbamazepine).


Concurrent use with probenecid or other drugs significantly eliminated by active renal tubular secretion may result in increased plasma concentrations of penciclovir.


Digoxin: Enoxacin may raise serum digoxin levels in some individuals.


Chlorpropamide: Chlorpropamides plasma half-life may be prolonged by allopurinol, since allopurinol and chlorpropamide may compete for excretion in the renal tubule.


Oral Contraceptives: Coadministration of atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol by approximately 30% and 20%.


Drugs that have been reported to diminish oral anticoagulant response, ie, decreased prothrom-bin time response, in man significantly include: adrenocortical steroids;alcohol*;antacids;antihistamines;barbiturates;carbamazepine;chloral hydrate*;chlordiazepoxide;cholestyramine;diet high in vitamin K;diuretics*;ethchlorvynol;glutethimide;griseofulvin;haloperidol;meprobamate;oral contraceptives;paraldehyde;primidone;ranitidine*;rifampin;unreliable prothrombin time determinations;vitamin C;warfarin sodium under-dosage.


Nicotine: Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.


Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;


The AUC and Cmax of both the (R) and (S) isomers of warfarin were unaffected by concurrent dosing of 0.3 mg cerivastatin sodium.


Urinary acidifying agents These agents (ammonium chloride, sodium acid phosphate, etc.) increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion.


Drugs and other substances demonstrated to be CYP 3A inhibitors on the basis of clinical studies involving benzodiazepines metabolized similarly to alprazolam or on the basis of in vitro studies with alprazolam or other benzodiazepines (caution is recommended during coadministration with alprazolam): Available data from clinical studies of benzodiazepines other than alprazolam suggest a possible drug interaction with alprazolam for the following: diltiazem, isoniazid, macrolide antibiotics such as erythromycin and clarithromycin, and grapefruit juice.


Interactions with Other CNS Agents: Concurrent use of Levo-Dromoran with all central nervous system depressants (eg, alcohol, sedatives, hypnotics, other opioids, general anesthetics, barbiturates, tricyclic antidepressants, phenothiazines, tranquilizers, skeletal muscle relaxants and antihistamines) may result in additive central nervous system depressant effects.


Both ibogaine and 18-MC block morphine-induced and nicotine-induced dopamine release in the nucleus accumbens;


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Probenecid : Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine).


- Lofexidine may enhance the effects of anti-hypertensive drug therapy


Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.


Multivalent Cation-Containing Products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.


Seizures have been reported in patients taking another quinolone class antimicrobial and the nonsteroidal anti-inflammatory drug fenbufen concurrently.


If desipramine hydrochloride is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of desipramine and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive.


Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.


However, due to possible pharmacodynamic interactions, when co-administered with PRECEDEX, a reduction in dosage of PRECEDEX on the concomitant anesthetic, sedative, hypnotic or opioid may be required.


The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or hypertension.


Coadministration of alosetron and strong CYP3A4 inhibitors, such as clarithromycin, telithromycin, protease inhibitors, voriconazole, and itraconazole has not been evaluated but should be undertaken with caution because of similar potential drug interactions.


The intensity, uniformity and time course of anticoagulant interference by phenobarbital, secobarbital, glutethimide, chloral hydrate and methaqualone were systematically investigated in 16 patients receiving coumarin therapy.


In some patients the combined use of indomethacin and diflunisal has been associated with fatal gastrointestinal hemorrhage.


Terfenadine: No clinically significant changes occurred in heart rate or corrected QT intervals, or in terfenadine metabolite or lomefloxacin pharmacokinetics, during concurrent administration of lomefloxacin and terfenadine at steady-state in 28 healthy males.


Warfarin, Digoxin, Salicylate, and Heparin The in vitro binding of warfarin to plasma proteins is only slightly reduced by ketorolac tromethamine (99.5% control vs 99.3%) when ketorolac plasma concentrations reach 5 to10 m g/mL.


If any signs or symptoms occur physicians should consider discontinuation of either one or both agents (ZYVOX or concomitant serotonergic agents).


Tablets: The benzodiazepines, including lorazepam, produce CNS-depressant effects when administered with such medications as barbiturates or alcohol.


In a comparison of digitalis tolerance in dogs anesthetized with ketamine, Innovar Vet, or pentobarbital, the dosage of ouabain needed to cause ventricular tachycardia was significantly higher, as was the LD50 of ouabain, with ketamine or Innovar than with pentobarbital.


Before taking glimepiride, tell your doctor if you are taking any of the following medicines: - aspirin or another salicylate such as magnesium/choline salicylate (Trilisate), salsalate (Disalcid, others), choline salicylate (Arthropan), magnesium salicylate (Magan), or bismuth subsalicylate (Pepto-Bismol);


In Europe, Nimotop  was observed to occasionally intensify the effect of antihypertensive compounds taken concomitantly by patients suffering from hypertension;


Oral Contraceptive: Based on AUC and half-life, multiple-dose pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of tablets containing 2.5 mg of norethindrone acetate and 50 mcg of ethinyl estradiol were similar with and without coadministration of gabapentin (400 mg TID;


When concomitant treatment with agents with b-blocking properties and clonidine is to be terminated, the b-blocking agent should be discontinued first.


Additive CNS depression may occur when antihistamines are administered concomitantly with other CNS depressants including barbiturates, tranquilizers, and alcohol.


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


The most commonly occurring drug interactions are listed below: - Drugs that may increase plasma phenytoin concentrations include: acute alcohol intake, amiodarone, chboramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone


Selegiline - L-phenylalanine and the selective MAO inhibitor selegiline may have synergistic antidepressant activity if used concomitantly.


Coadministration of valdecoxib (40 mg BID (day 1) and 40 mg QD (days 2-7)) with glyburide (10 mg glyburide BID) resulted in 21% increase in glyburide AUC0-12 and a 16% increase in glyburide Cmax leading to a 16% decrease in glucose AUC0-24.


Fulminant rhabdomyolysis has been seen as early as three weeks after initiation of combined therapy with another fibrate and lovastatin but may be seen after several months.


Nonsteroidal anti-inflammatory agents (NSAIDS): Concomitant use of aspirin (or other nonsteroidal antiinflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects.


Therefore, co-administration of tricyclic antidepressants with other drugs that are metabolized by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (eg, propafenone, flecainide, and encainide), or that inhibit this enzyme (eg, quinidine), should be approached with caution.


CONCLUSIONS: Macrolide antibiotics inhibit the metabolism of HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivastatin, lovastatin, simvastatin).


Effects of Other Antiepileptic Drugs on Felbatol  Phenytoin: Phenytoin causes an approximate doubling of the clearance of Felbatol  (felbamate) at steady state and, therefore, the addition of phenytoin causes an approximate 45% decrease in the steady-state trough concentrations of Felbatol  as compared to the same dose of Felbatol  given as monotherapy.


In vivo studies: Nitrates: The blood pressure lowering effects of sublingual nitrates (0.4 mg) taken 1 and 4 hours after vardenafil and increases in heart rate when taken at 1, 4 and 8 hours were potentiated by a 20 mg dose of Vardenafil in healthy middle-aged subjects.


The hypoglycemic effect of tolbutamide has been reported to increase when Atromid-S is given concurrently.


There has been too little experience with the coadministration of TAMBOCOR with nifedipine or diltiazem to recommend concomitant use.


EDECRIN may increase the ototoxic potential of other drugs such as aminoglycoside and some cephalosporin antibiotics.


Aspirin/Acetaminophen: Pharmacokinetic or pharmacodynamic drug-drug interactions have not been demonstrated between Argatroban and concomitantly administered aspirin (162.5 mg orally given 26 and 2 hours prior to initiation of Argatroban 1  g/kg/min. over 4 hours) or acetaminophen (1000 mg orally given 12, 6 and 0 hours prior to, and 6 and 12 hours subsequent to, initiation of Argatroban 1.5  g/kg/min. over 18 hours).


Multivitamins, or other products containing iron or zinc, antacids or sucralfate should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because they may interfere with absorption resulting in lower serum and urine levels of norfloxacin.


Immediate and Extended Release Tablets The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents.


Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been rarely reported to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists.


Drugs that have been reported to diminish oral anticoagulant response, ie, decreased prothrom-bin time response, in man significantly include: adrenocortical steroids;alcohol*;antacids;antihistamines;barbiturates;carbamazepine;chloral hydrate*;chlordiazepoxide;cholestyramine;diet high in vitamin K;diuretics*;ethchlorvynol;glutethimide;griseofulvin;haloperidol;meprobamate;oral contraceptives;paraldehyde;primidone;ranitidine*;rifampin;unreliable prothrombin time determinations;vitamin C;warfarin sodium under-dosage.


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.


The following are examples of substances that may reduce the blood-glucose-lowering effect: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives).


Therefore, co-administration of clozapine with other drugs that are metabolized by this isozyme, including antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution.


The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects on prolonging atrioventricular conduction time.


The concomitant use of other CYP3A4 inhibitors such as diltiazem and erythromycin with transdermal fentanyl may also result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause serious respiratory depression.


Interactions with Mixed Agonist/Antagonist Opioid Analgesics: Agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol, dezocine and buprenorphine) should NOT be administered to a patient who has received or is receiving a course of therapy with a pure agonist opioid analgesic such as Levo-Dromoran.


The AUC of eszopiclone was increased 2.2-fold by coadministration of ketoconazole, a potent inhibitor of CYP3A4, 400 mg daily for 5 days.


Nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as furosemide.


Phenytoin: Population pharmacokinetic analyses indicate that tiagabine clearance is 60% greater in patients taking phenytoin with or without other enzyme- inducing AEDs.


Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A4 (enzyme induction).


A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients.


The plasma maximum concentration and area under the plasma concentration-time curve of diltiazem, desacetyldiltiazem, and desmethyldiltiazem were unchanged after coadministration of sirolimus, and no potentiation of the effects of diltiazem on diastolic or systolic blood pressure or on the electrocardiographic parameters was seen.


Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to SUSTIVA.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine.


During administration of multiple oral doses of TAMBOCOR to healthy subjects stabilized on a maintenance dose of digoxin, a 13%-19% increase in plasma digoxin levels occurred at six hours postdose.


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


Monoamine oxidase (MAO) inhibitors such as isocarboxazid (e.g., Marplan), phenelzine (e.g., Nardil), procarbazine (e.g., Matulane), selegiline (e.g., Eldepryl), and tranylcypromine (e.g., Parnate): Using these medicines with L-tryptophan may increase the chance of side effects.


Tagamet, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Azithromycin had no significant impact on the Cmax and AUC of zidovudine, although it significantly decreased the zidovudine tmax by 44% and increased the intracellular exposure to phosphorylated zidovudine by 110%.


In patients receiving mercaptopurine (Purinethol) or azathioprine (Imuran), the concomitant administration of 300-600 mg of allopurinol per day will require a reduction in dose to approximately one-third to one-fourth of the usual dose of mercaptopurine or azathioprine.


Other Cardiovascular Agents: Enalapril and enalapril IV have been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions.


Before taking glimepiride, tell your doctor if you are taking any of the following medicines: - aspirin or another salicylate such as magnesium/choline salicylate (Trilisate), salsalate (Disalcid, others), choline salicylate (Arthropan), magnesium salicylate (Magan), or bismuth subsalicylate (Pepto-Bismol);


Saquinavir: Coadministration of saquinavir (using an experimental soft-gelatin capsule formulation of saquinavir 1200mg) with VIRACEPT resulted in an 18% increase in nelfinavir plasma AUC and a 4-fold increase in saquinavir plasma A.C.


- a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil, Nuprin, others), ketoprofen (Orudis, Orudis KT, Oruvail), diclofenac (Voltaren, Cataflam), etodolac (Lodine), indomethacin (Indocin), nabumetone (Relafen), oxaprozin (Daypro), and naproxen (Anaprox, Naprosyn, Aleve);


No interaction with the tricyclic antidepressant imipramine was shown in a single-dose study with entacapone without coadministered levodopa/dopa-decarboxylase inhibitor.


Drugs that have been reported to diminish oral anticoagulant response, ie, decreased prothrom-bin time response, in man significantly include: adrenocortical steroids;alcohol*;antacids;antihistamines;barbiturates;carbamazepine;chloral hydrate*;chlordiazepoxide;cholestyramine;diet high in vitamin K;diuretics*;ethchlorvynol;glutethimide;griseofulvin;haloperidol;meprobamate;oral contraceptives;paraldehyde;primidone;ranitidine*;rifampin;unreliable prothrombin time determinations;vitamin C;warfarin sodium under-dosage.


Patients who begin taking diclofenac or who increase their diclofenac dose or any other NSAID while taking digoxin, methotrexate, or cyclosporine may develop toxicity characteristics for these drugs.


Furosemide: When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced by about 30% and 50%, respectively.


Imidazoles (e. g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.): in vitro and animal studies with the combination of amphotericin B and imidazoles suggest that imidazoles may induce fungal resistance to amphotericin B.


Binding to Serum Proteins: The following agents may either inhibit levothyroxine sodium binding to serum proteins or alter the concentrations of serum binding proteins: androgens and related anabolic hormones, asparaginase, clofibrate, estrogens and estrogen-containing compounds, 5-fluorouracil, furosemide, glucocorticoids, meclofenamic acid, mefenamic acid, methadone, perphenazine, phenylbutazone, phenytoin, salicylates, tamoxifen.


Nevertheless, caution is indicated in the co-administration of T.A. with any of the SSRIs and also in switching from one class to the other.


Multivalent Cation-Containing Products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.


Chlorotrianisene may interact with antidepressants, aspirin, barbiturates, bromocriptine, calcium supplements, corticosteroids, corticotropin, cyclosporine, dantrolene, nicotine, somatropin, tamoxifen, and warfarin.


In vitro data suggest that itraconazole, when compared to ketoconazole, has a less pronounced effect on the biotransformation system responsible for the metabolism of astemizole.


Therefore, concurrent use of Trileptal with hormonal contraceptives may render these contraceptives less effective.


plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well.


Co-medications that induce CYP 3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John s wort) may significantly decrease exposure to exemestane.


Quinolones, including norfloxacin, may enhance the effects of oral anticoagulants, including warfarin or its derivatives or similar agents.


Chloral hydrate and methaqualone interact pharmacologically with orally administered anticoagulant agents, but the effect is not clinically significant.


Warfarin-Vitamin K can antagonize the effect of warfarin


Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Nevirapine may decrease plasma levels of combination hormonal contraceptives;


If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.


Drugs which induce CYP3A4 activity (eg, phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of efavirenz resulting in lowered plasma concentrations.


Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin or minocycline.


Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;


Vitamin A: Because of the relationship of Accutane to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects


FLEXERIL may enhance the effects of alcohol, barbiturates, and other CNS depressants.


Alpha-blockers: When Vardenafil 10 or 20 mg was given to healthy volunteers either simultaneously or 6 hours after a 10 mg dose of terazosin, significant hypotension developed in a substantial number of subjects.


Fluvoxamine increased mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold.


Felbamate treatment resulted in a 42% decrease in the gestodene AUC 0-24, but no clinically relevant effect was observed on the pharmacokinetic parameters of ethinyl estradiol.


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents.


Administration of quinolones with antacids containing aluminum, magnesium, or calcium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as VIDEX (didanosine) chewable/buffered tablets or the pediatric powder for oral solution, may substantially interfere with the absorption of quinolones, resulting in systemic concentrations considerably lower than desired.


Coumarin Anticoagulants Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.


Beta-adrenergic blocking agents: Coadministration of beta-adrenergic blocking agents did not have any effect on either the safety or efficacy of ibutilide in the clinical trials.


On administration of oral amiodarone, the need for digitalis therapy should be reviewed and the dose reduced by approximately 50% or discontinued.


Because of foscarnets tendency to cause renal impairment, the use of FOSCAVIR should be avoided in combination with potentially nephrotoxic drugs such as aminoglycosides, amphotericin B and intravenous pentamidine unless the potential benefits outweigh the risks to the patient.


Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin andtolbutamide did not alter ketorolac tromethamine protein binding.


Potassium-depleting diuretics are a major contributing factor to digitalis toxicity.


Cholestyramine, an anionic-binding resin, has a considerable effect in lowering the rate and extent of fluvastatin bioavailability.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


Although concomitant use of Clozapine and carbamazepine is not recommended, it should be noted that discontinuation of concomitant carbamazepine administration may result in an increase in Clozapine plasma levels.


Antacids: In a clinical pharmacology study, coadministration of an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril administered alone, suggesting that antacids may impair absorption of fosinopril.


acetaminophen/theophylline, lidocaine/quinidine, phenobarbital/acetaminophen, phenobarbital/valproic acid, quinidine/lidocaine, theophylline/acetaminophen, and valproic acid/phenobarbital.


Cyclosporine - L-arginine may counteract the antinaturetic effect of cyclosporin.


If desipramine hydrochloride is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of desipramine and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive.


Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.


Increasing the felbamate dose to 1800 mg/day in six of these subjects increased the steady-state phenytoin Cmin to 25 7 micrograms/mL.


Antacids: In a single dose study (n=6), ingestion of an antacid containing 1.7-gram of magnesium hydroxide with 500-mg of mefenamic acid increased the Cmax and AUC of mefenamic acid by 125% and 36%, respectively.  A number of compounds are inhibitors of CYP2C9 including fluconazole, lovastatin and trimethoprim.


In addition, several AED s that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD.


A dose increase of lopinavir/ritonavir to 533/133 mg twice daily with food isrecommended in combination with nevirapine.


In clinical trials, FLOLAN was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom therapy with FLOLAN was initiated, apparent oral clearance values for furosemide (n = 23) and digoxin (n = 30) were decreased by 13% and 15%, respectively, on the second day of therapy and had returned to baseline values by day 87.


Since Zarontin (ethosuximide) may interact with concurrently administered antiepileptic drugs, periodic serum level determinations of these drugs may be necessary (eg, ethosuximide may elevate phenytoin serum levels and valproic acid has been reported to both increase and decrease ethosuximide levels).


Although acid-base and electrolyte disturbances were not reported in the clinical trials with dorzolamide, these disturbances have been reported with oral carbonic anhydrase inhibitors and have, in some instances, resulted in drug interactions (e.g., toxicity associated with high-dose salicylate therapy).


In a single subject given one dose of ciprofloxacin 2 hours after a dose of didanosine-placebo tablets, a greater than 50% reduction in the AUC of ciprofloxacin was observed.


As with other antihypertensive agents, the antihypertensive effect of losartan may be blunted by the non-steroidal anti-inflammatory drug indomethacin


Concomitant administration of alosetron and fluvoxamine is contraindicated.


Fluconazole: Concomitant administration of fluconazole at 200 mg QD resulted in a two-fold increase in celecoxib plasma concentration.


Antacid: The effect of an aluminum hydroxide- and magnesium hydroxide-containing antacid (Maalox)* on the pharmacokinetics of capecitabine was investigated in 12 cancer patients.


Therefore, co-administration of bupropion with drugs that are metabolized by CYP2D6 isoenzyme including certain antidepressants (e.g., nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication.


Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.


Studies in humans show that the absorption of chlorothiazide as reflected in urinary excretion is markedly decreased even when administered one hour before colestipol hydrochloride.


Co-administration of lovastatin, atenolol, warfarin, furosemide, digoxin, celecoxib, hydrochlorothiazide, ramipril, valsartan, metformin and amlodipine did not result in clinically significant increases in aliskiren exposure.


Nitrofurantoin interferes with the therapeutic action of nalidixic acid.


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Rifampin: Rifampin increases the metabolism of ethinyl estradiol and some progestins (norethindrone) resulting in decreased contraceptive effectiveness and increased menstrual irregularities.


Before taking glimepiride, tell your doctor if you are taking any of the following medicines: - aspirin or another salicylate such as magnesium/choline salicylate (Trilisate), salsalate (Disalcid, others), choline salicylate (Arthropan), magnesium salicylate (Magan), or bismuth subsalicylate (Pepto-Bismol);


It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


Loperamide and morphine (0.1 and 1.0 mg/kg, s.c.) inhibited the dmPGE2 (0.3 mg/kg, p.o.)-induced diarrhea in cecectomized rats.


Agents Causing Renin Release: The antihypertensive effect of enalapril and enalapril IV is augmented by antihypertensive agents that cause renin release (e.g., diuretics).


Iron salts may reduce the bioavailability of carbidopa and levodopa.


Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists.


The fraction of STADOL NS absorbed is unaffected by the concomitant administration of a nasal vasoconstrictor (oxymetazoline), but the rate of absorption is decreased.


Phenothiazine-related compounds and beta-adrenergic blocking agents may have additive hypotensite effects due to the inhibition of each other s metabolism.


The AUC of ciprofloxacin was decreased an average of 15-fold in 12 healthy subjects given ciprofloxacin and didanosine-placebo tablets concurrently.


Cyclosporine: Because cyclosporine can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including TRICOR, there is a risk that an interaction will lead to deterioration.


In the first study, concomitant administration of 0.2 mg cerivastatin sodium and 12 g cholestyramine resulted in decreases of more than 22% for AUC and 40% for Cmax when compared to dosing cerivastatin sodium alone.


Since Zarontin (ethosuximide) may interact with concurrently administered antiepileptic drugs, periodic serum level determinations of these drugs may be necessary (eg, ethosuximide may elevate phenytoin serum levels and valproic acid has been reported to both increase and decrease ethosuximide levels).


The anxiogenic effects of theophylline were reduced by pretreatment with CGS 21680, an A2-selective agonist, but not by N6-cyclopentyladenosine (CPA), an A1-selective agonist.


These results would seem to dictate against the clinical use of methotrexate with ELSPAR, or during the period following ELSPAR therapy when plasma asparagine levels are below normal.


Therefore, esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts and digoxin).


- Drugs whose efficacy is impaired by phenytoin include: anticoagulants, corticosteroids, coumarin, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, rifampin, quinidine, theophylline, vitamin D.


Likewise, gabapentin pharmacokinetics were unaltered by carbamazepine administration.


d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain;


Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;


Although specific drug interaction studies have not been conducted with ALPHAGAN P, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.


Certain drugs, including nonsteroidal anti-inflammatory agents (NSAIDs), salicylates, monoamine oxidase inhibitors, and non-selective beta-adrenergic-blocking agents may potentiate the hypoglycemic action of Starlix and other oral antidiabetic drugs.


Central Nervous System Depressants: The concomitant use of DURAGESIC  (fentanyl transdermal system) with other central nervous system depressants, including but not limited to other opioids, sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol, may cause respiratory depression, hypotension, and profound sedation, or potentially result in coma or death.


Phenytoin/Phenobarbital: The coadministration of phenytoin or phenobarbital will not affect plasma concentrations of vitamin D, but may reduce endogenous plasma levels of calcitriol/ergocalcitriol by accelerating metabolism.


In patients receiving another serotonin reuptake inhibitor drug in combination with monoamine oxidase inhibitors (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.


Glibenclamide: In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects.


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


However, caution should be exercised because there have been a few spontaneous reports of prolonged prothrombin times, with or without bleeding, in etodolac-treated patients receiving concomitant warfarin therapy.


Sympathomimetic amines may reduce the antihypertensive effects of reserpine, veratrum alkaloids, methyldopa and mecamylamine.


In clinical trials, FLOLAN was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom therapy with FLOLAN was initiated, apparent oral clearance values for furosemide (n = 23) and digoxin (n = 30) were decreased by 13% and 15%, respectively, on the second day of therapy and had returned to baseline values by day 87.


Indinavir steady-state Cmax, A.C. and Cmin were decreased by 22%, 38%, and 27%, respectively, by concomitant amprenavir.


Anticonvulsants (carbamazepine, felbamate, phenobarbital, phenytoin, topiramate): Increase the metabolism of ethinyl estradiol and/or some progestins, leading to possible decrease in contraceptive effectiveness.


Although it has not been established that there is an interaction between Clozapine and benzodiazepines or other psychotropics, caution is advised when clozapine is initiated in patients taking a benzodiazepine or any other psychotropic drug.


Dolasetron mesylate did not inhibit the antitumor activity of four chemotherapeutic agents (cisplatin, 5-fluorouracil, doxorubicin, cyclophosphamide) in four murine models.


Drug Interactions: The central anticholinergic syndrome can occur when anticholinergic agents such as AKINETON are administered concomitantly with drugs that have secondary anticholinergic actions, e.g., certain narcotic analgesics such as meperidine, the phenothiazines and other antipsychotics, tricyclic antidepressants, certain antiarrhythmics such as the quinidine salts, and antihistamines.


The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension.


Imidazoles (e. g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.): in vitro and animal studies with the combination of amphotericin B and imidazoles suggest that imidazoles may induce fungal resistance to amphotericin B.


A direct causal relationship has not been established, but physicians should consider the possibility that diclofenac may alter a diabetic patient s response to insulin or oral hypoglycemic agents.


Therefore, when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained.


Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving SPRYCEL.


Barbiturates, phenytoin, or rifampin increased metabolic clearance of fludrocortisone acetate because of the induction of hepatic enzymes.


However, in a well-controlled study of patients with lymphoma on combination therapy, allopurinol did not increase the marrow toxicity of patients treated with cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechlorethamine.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


Death due to fulminant pancreatitis possibly related to intravenous pentamidine and HIVID has been reported.


The purpose of this study was to evaluate the effect of sodium carboxymethylcellulose (NaCMC) and carboxymethylcellulose-cysteine (CMC-Cys) conjugates on the intestinal permeation of sodium fluorescein (NaFlu) and model peptide drugs, bacitracin and insulin.


In addition, Fondaparinux neither influenced the pharmacodynamics of warfarin, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state.


Cyclosporine: Combination hormonal contraceptives may inhibit the metabolism of cyclosporine, leading to increased plasma concentrations;


Magnesium: Magnesium-containing preparations (eg, antacids) may cause hypermagnesemia and should therefore not be taken during therapy with vitamin D by patients on chronic renal dialysis.


When duloxetine was administered (at a dose of 60 mg BID) in conjunction with a single 50-mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold.


Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*;allopurinol;aminosalicylic acid;amiodarone;anabolic steroids;antibiotics;bromelains;chloral hydrate*;chlorpropamide;chymotrypsin;cimetidine;cinchophen;clofibrate;dextran;dextrothyroxine;diazoxide;dietary deficiencies;diflunisal;disulfiram;drugs affecting blood elements;ethacrynic acid;fenoprofen;glucagon;hepatotoxic drugs;ibuprofen;indomethacin;influenza virus vaccine;inhalation anesthetics;mefenamic acid;methyldopa;methylphenidate;metronidazole;miconazole;monoamine oxidase inhibitors;nalidixic acid;naproxen;oxolinic acid;oxyphenbutazone;pentoxifylline;phenylbutazone;phenyramidol;phenytoin;prolonged hot weather;prolonged narcotics;pyrazolones;quinidine;quinine;ranitidine*;salicylates;sulfinpyrazone;sulfonamides, long acting;sulindac;thyroid drugs;tolbutamide;triclofos sodium;trimethoprim/sulfamethoxazole;unreliable prothrombin time determinations;warfarin sodium overdosage.


Adrenergic blockers: Adrenergic blockers are inhibited by amphetamines.


Protease inhibitors: Amprenavir, lopinavir, nelfinavir, and ritonavir have been shown to decrease plasma levels of combination hormonal contraceptives;


Agents that are CYP3A4 inhibitors that have been found, or are expected, to increase plasma levels of EQUETROTM are the following: Acetazolamide, azole antifungals, cimetidine, clarithromycin(1), dalfopristin, danazol, delavirdine, diltiazem, erythromycin(1), fluoxetine, fluvoxamine, grapefruit juice, isoniazid, itraconazole, ketoconazole, loratadine, nefazodone, niacinamide, nicotinamide, protease inhibitors, propoxyphene, quinine, quinupristin, troleandomycin, valproate(1), verapamil, zileuton.


In addition, drugs that are actively secreted via this route (e.g., triamterene, metformin and amiloride) should be co-administered with care as they might increase dofetilide levels.


Anticholinesterases: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis.


Fentanyl Anesthesia: Severe hypotension has been reported during fentanyl anesthesia with concomitant use of a beta blocker and a calcium channel blocker.


A dose increase of lopinavir/ritonavir to 533/133 mg (4 capsules or 6.5 mL) twice daily taken with food is recommended when used in combination with SUSTIVA.


Lithium: Valdecoxib 40 mg BID for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone.


Quinidine: Immediate Release Capsules: There have been rare reports of an interaction between quinidine and nifedipine (with a decreased plasma level of quinidine).


As the primary effect of adenosine is to decrease conduction through the A-V node, higher degrees of heart block may be produced in the presence of carbamazepine.


Because the nitrosourea CCNU is given exclusively by the oral route in man, we have carried out studies in mice on the antitumour activity, acute toxicity and pharmacokinetics of oral CCNU, either alone or in combination with the chemosensitizer misonidazole.


In patients receiving nonselective monoamine oxidase inhibitors (MAOIs) (e.g., selegiline hydrochloride) in combination with serotoninergic agents (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine), there have been reports of serious, sometimes fatal, reactions.


Digitalis: Vitamin D dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcemia in such patients may precipitate cardiac arrhythmias.


Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as NUROMAX include certain antibiotics (e. g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistimethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine.


MAO inhibitors: MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism.


Use with Angiotensln Converting Enzyme Inhibitors: The use of angiotensin converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to induce severe leukopenia.


Amphotericin B or potassium-depleting diuretics (benzothiadiazines and related drugs, ethacrynic acid and furosemide) enhanced hypokalemia.


The most commonly occurring drug interactions are listed below: - Drugs that may increase plasma phenytoin concentrations include: acute alcohol intake, amiodarone, chboramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone


When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine.


Furthermore, rifampin, phenytoin, phenobarbital, and other inducers of cytochrome P450 3A4 may cause a reduction in plasma bexarotene concentrations.


Butalbital, acetaminophen and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.


Antacids: In a clinical pharmacology study, coadministration of an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril administered alone, suggesting that antacids may impair absorption of fosinopril.


Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline): Metabolism may be inhibited by combination hormonal contraceptives, increasing plasma levels of antidepressant;


Sodium cephalothin may enhance the nephrotoxicity of Coly-Mycin M Parenteral.


Additional iron significantly inhibited the absorption of cobalt in both dietary cobalt treatments.


Inhibitors or substrates of CYP2D6 (i.e., quinidine, selective serotonin reuptake inhibitors [SSRIs]) may increase the plasma concentration of doxepin when administered concomitantly.


Drugs that have been reported to diminish oral anticoagulant response, ie, decreased prothrom-bin time response, in man significantly include: adrenocortical steroids;alcohol*;antacids;antihistamines;barbiturates;carbamazepine;chloral hydrate*;chlordiazepoxide;cholestyramine;diet high in vitamin K;diuretics*;ethchlorvynol;glutethimide;griseofulvin;haloperidol;meprobamate;oral contraceptives;paraldehyde;primidone;ranitidine*;rifampin;unreliable prothrombin time determinations;vitamin C;warfarin sodium under-dosage.


Drugs Demonstrated to be CYP 3A Inhibitors of Possible Clinical Significance on the Basis of Clinical Studies Involving Alprazolam (caution is recommended during coadministration with alprazolam): Coadministration of fluoxetine with alprazolam increased the maximum plasma concentration of alprazolam by 46%, decreased clearance by 21%, increased half-life by 17%, and decreased measured psychomotor performance.


In a study in which the 2 mg clonazepam orally disintegrating tablet was administered with and without propantheline (an anticholinergic agent with multiple effects on the GI tract) to healthy volunteers, the AUC of clonazepam was 10% lower and the Cmax of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to when it was given alone.


Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)-A drug interaction study of eplerenone with an NSAID has not been conducted.


Caution is advised when TRISENOX is coadministered with other medications that can prolong the QT interval (e.g. certain antiarrhythmics or thioridazine) or lead to electrolyte abnormalities (such as diuretics or amphotericin B).


- Phenothiazines (acetophenazine [e.g., Tindal], chlorpromazine [e.g., Thorazine], fluphenazine [e.g., Prolixin], mesoridazine [e.g., Serentil], perphenazine [e.g., Trilafon], prochlorperazine [e.g., Compazine], promazine [e.g., Sparine], promethazine [e.g., Phenergan], thioridazine [e.g., Mellaril], trifluoperazine [e.g., Stelazine], triflupromazine [e.g., Vesprin], trimeprazine [e.g., Temaril]) or


Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive.


Because of the potential for ARAVA levels to continue to increase with multiple dosing, caution should be used if patients are to be receiving both ARAVA and rifampin.


In vitro displacement studies with highly protein-bound drugs such as furosemide, propranolol, captopril, nicardipine, pravastatin, glyburide, warfarin, phenytoin, acetylsalicylic acid, tolbutamide, and metformin showed no influence on the extent of nateglinide protein binding.


Data suggest that coadministration of oral ketoconazole and cisapride can result in prolongation of the QT interval on the ECG.


THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS SUCH AS NARCOTICS, NON-NARCOTIC ANALGESICS AND BARBITURATES.


Concomitant treatment with methylxanthines (aminophylline, theophylline), steroids, or diuretics may potentiate any hypokalemic effect of adrenergic agonists.


Therefore, co-administration of clozapine with other drugs that are metabolized by this isozyme, including antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution.


Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide.


Multivalent Cation-Containing Products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.


Coadministration of alosetron and strong CYP3A4 inhibitors, such as clarithromycin, telithromycin, protease inhibitors, voriconazole, and itraconazole has not been evaluated but should be undertaken with caution because of similar potential drug interactions.


There have been greater than two-fold increases of previously stable plasma levels of tricyclic antidepressants when fluoxetine has been administered in combination with these agents.


Coumarin Anticoagulants Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.


Acidifying agents: Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines.


Nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as furosemide.


There have been reports of theophylline-related side effects in patients on concomitant therapy with quinolones and theophylline.


Tagamet, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.


Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.


The effect of TORADOL on plasma lithium has not been studied, but cases of increased lithium plasma levels during TORADOL therapy have been reported.


In one controlled clinical study, the ureidopenicillins, including piperacillin, were reported to prolong the action of vecuronium.


Interactions with Other CNS Agents: Concurrent use of Levo-Dromoran with all central nervous system depressants (eg, alcohol, sedatives, hypnotics, other opioids, general anesthetics, barbiturates, tricyclic antidepressants, phenothiazines, tranquilizers, skeletal muscle relaxants and antihistamines) may result in additive central nervous system depressant effects.


Co-administration of CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several- fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism.


In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200 m m M i.e., 350 mg/L) was 17-28%.


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Certain drugs including thiazides, corticosteroids, thyroid products, and sympathomimetics may reduce the hypoglycemic action of Starlix and other oral antidiabetic drugs.


If treatment with inhibitors of CYP3A4 activity (such as ketoconazole, intraconazole, ritonavir, indinavir, saquinavir, erythromycin, etc.) is indicated, reduction of the budesonide dose should be considered.


Clinical studies in healthy volunteers show that the pharmacokinetics of CANCIDAS are not altered by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus.


Binding to Serum Proteins: The following agents may either inhibit levothyroxine sodium binding to serum proteins or alter the concentrations of serum binding proteins: androgens and related anabolic hormones, asparaginase, clofibrate, estrogens and estrogen-containing compounds, 5-fluorouracil, furosemide, glucocorticoids, meclofenamic acid, mefenamic acid, methadone, perphenazine, phenylbutazone, phenytoin, salicylates, tamoxifen.


When lansoprazole was administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen.


Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;


Patients receiving other narcotic analgesics, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with hydrocodone and acetaminophen tablets may exhibit an additive CNS depression.


When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine.


No drug interaction studies have been conducted for COLAZAL, however the use of orally administered antibiotics could, theoretically, interfere with the release of mesalamine in the colon.


Avoid the use of preparations such as decongestants and local anesthetics which contain any sympathomimetic amine (e.g., epinephrine, norepinephrine), since it has been reported that tricyclic antidepressants can potentiate the effects of catecholamines.


ACE-inhibitors:Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors.


Drug Interactions: Flupenthixol may interact with some drugs, like Monoamine oxidase inhibitors (MAOI): MAOI could theoretically affect flupenthixol pharmacodynamics - Arecoline - Eproxindine - Ethanol: Flupenthixol and Ethanol cause additive CNS depression - Tricyclic antidepressants: Flupenthixol increases the effect of Tricyclic antidepressants


The following agents may increase certain actions or side effects of anticholinergic drugs. amantadine antiarrhythmic agents of class (e.g. quinidine), antihistamines antipsychotic agents (e.g. phenothiazines), benzodiazepines.


Multivalent Cation-Containing Products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.


In a study in diabetics with microalbuminuria INSPRA 200 mg combined with the ACE inhibitor enalapril 10 mg increased the frequency of hyperkalemia (serum potassium  5.5 mEq/L) from 17% on enalapril alone to 38%.


The effects of supplementary oral cobalt and iron, as well as the interaction between both at the absorption site, fecal and urinary excretion as well as the retention of these trace elements were determined by using four diets containing either 9 or 63 micrograms/kg of Co and 48 or 446 mg/kg of Fe over a period of 19 days in a total of 24 rats.


Population pharmacokinetic analyses revealed that MTX, NSAIDs, corticosteroids, and TNF blocking agents did not influence abatacept clearance.


Lithium: Nonsteroidal anti-inflammatory agents have been reported to increase steadystate plasma lithium levels.


Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C.


Therefore, interactions could occur following concomitant administration of psychotropic drugs (e.g., narcotics, analgesics, antiemetics, sedatives, tranquilizers).


Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.


Drugs Whose Absorption Can Be Affected by the Level of Acidity in the Stomach: Drugs such as ketoconazole and itraconazole should be administered at least 2 hours prior to dosing with VIDEX.


Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving SPRYCEL.


Consequently, concomitant administration of Aprepitant with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) should be approached with caution.


Both the magnitude and duration of central nervous system and cardiovascular effects may be enhanced when ALFENTA is administered in combination with other CNS depressants such as barbiturates, tranquilizers, opioids, or inhalation general anesthetics.


Coadministration of CRIXIVAN and other drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir.


Cytochrome P-450 inducers, such as phenytoin, carbamazepine and phenobarbital, induce clonazepam metabolism, causing an approximately 30% decrease in plasma clonazepam levels.


However, because some quinolones have been reported to enhance the anticoagulant effects of warfarin or its derivatives in patients, the prothrombin time or other suitable coagulation test should be closely monitored if a quinolone antimicrobial is administered concomitantly with warfarin or its derivatives.


Griseofulvin: Griseofulvin may induce the metabolism of combination hormonal contraceptives causing menstrual changes;


Another oral azole antifungal, ketoconazole, inhibits the metabolism of astemizole, resulting in elevated plasma concentrations of astemizole and its active metabolite desmethylastermizole which may prolong QT intervals.


Using calcium acetate with digitalis glycosides (heart medicine) may cause hypercalcemia (too much calcium in the blood), which could increase the chance of developing an irregular heartbeat.


Bentiromide may interact with acetaminophen (e.g., Tylenol), chloramphenicol (e.g., Chloromycetin), local anesthetics (e.g., benzocaine and lidocaine), para-aminobenzoic acid (PABA)-containing preparations (e.g., sunscreens and some multivitamins), procainamide (e.g., Pronestyl), sulfonamides (sulfa medicines), thiazide diuretics (use of these medicines during the test period will affect the test results), and pancreatic supplements (use of pancreatic supplements may give false test results).


Based on adult data, lower doses of caffeine may be needed following coadministration of drugs which are reported to decrease caffeine elimination (e.g., cimetidine and ketoconazole) and higher caffeine doses may be needed following coadministration of drugs that increase caffeine elimination (e.g., phenobarbital and phenytoin).


however, 150 mg of ranitidine q12h for 3 days increased the ceftibuten C max by 23% and ceftibuten AUC by 16%.


In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective.


Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3-4 fold and the Cmax by 2-fold, compared to placebo.


conversely, diethylpropion may interfere with antihypertensive drugs (i.e., guanethidine, a-methyldopa).


Interactions with Other CNS Agents: Concurrent use of Levo-Dromoran with all central nervous system depressants (eg, alcohol, sedatives, hypnotics, other opioids, general anesthetics, barbiturates, tricyclic antidepressants, phenothiazines, tranquilizers, skeletal muscle relaxants and antihistamines) may result in additive central nervous system depressant effects.


Coadministration with compounds that are potent inducers of CYP3A4 (eg, phenobarbital, phenytoin, dexamethasone, carbamazepine) may result in decreased plasma levels of saquinavir.


The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension.


Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion.


Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.


butyrophenone classes of antipsychotic agents


Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these benzodiazepines.


In patients who have been reported to be well controlled on tricyclic antidepressants receiving concurrent cimetidine therapy, discontinuation of cimetidine has been reported to decrease established steady-state serum tricyclic antidepressant levels and compromise their therapeutic effects.


Sodium thiosulfate is a neutralizing agent for cisplatin that protects against renal damage.


Furosemide: Clinical studies, as well as random observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients.


Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.


Probenecid: The oral combination of probenecid before intramuscular injection of PIPRACIL produces an increase in piperacillin peak serum level of about 30%.


In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism.


Cisapride should not be used concomitantly with other drugs known to prolong the QT interval: certain antiarrhythmics, including those of Class IA (such as quinidine and procainamide) and Class III (such as sotalol);


There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, tacrolimus, hexobarbital, phenytoin, alfentanil, cisapride, disopyramide, lovastatin, bromocriptine, valproate, terfenadine, and astemizole.


Catecholamine-depleting Agents: Patients taking both agents with b-blocking properties and a drug that can deplete catecholamines (e.g., reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia.


Intravenous ranitidine was shown to double the bioavailability of oral alendronate.


- Drugs whose efficacy is impaired by phenytoin include: anticoagulants, corticosteroids, coumarin, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, rifampin, quinidine, theophylline, vitamin D.


Cimetidine: Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level.


However, high doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate.


Beta-blockers not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in COPD patients.


Paroxetine (20 mg QD) increased the concentration of duloxetine (40 mg QD) by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine.


The serum estrogen concentrations of estradiol + endotoxin-treated rats decreased by 50%, while those of the endotoxin-treated rats increased (2- to 5-fold).


Therefore, co-administration of tricyclic antidepressants with other drugs that are metabolized by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (eg, propafenone, flecainide, and encainide), or that inhibit this enzyme (eg, quinidine), should be approached with caution.


Lithium generally should not be given with diuretics because they reduce lithiums renal clearance and add a high risk of lithium toxicity.


However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving systemic cyclosporine concomitantly.