Erythromycin with carbamazepine

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

Carbamazepine may interact with other drugs by inducing their metabolism. Valproic acid increases concentrations ofthe 10,11-epoxide metabolite without affecting the concentration of carbamazepine. The interaction of erythromycin and clarithromycin (CYP3A4 inhibition) with carbamazepine is particularly significant. 

Erythromycin Carbamazepine Phenytoin Valproate Risk of toxicity particularly with carbamazepine Inhibition of metabolism of the affected drugs... 

Suitability for patient The item prescribed (erythromycin) is unsuitable for this patient as it will interact with his carbamazepine. You need to advise the dentist of the potentially serious interaction between erythromycin and carbamazepine and suggest an alternative. A usual alternative antibiotic would be a penicillin however, you are also aware that the patient is penicillin sensitive. Therefore, another choice would be metronidazole 200 mg tds for 3 days (see 4 above) which will not interact with the carbamazepine, is suitable for a penicillin-sensitive patient and is allowable on NHS dental prescriptions. Ask the dentist to provide a new prescription. 

Anti-infective drugs Ciprofloxacin can greatly increase the risk of seizure induction in patients taking anticonvulsants. Erythromycin produces a rapid 100-200% rise in carbamazepine levels. There is a possibility of reduced plasma levels of the protease inhibitors indinavir and saquinavir with carbamazepine. Isoniazid increases carbamazepine serum levels, and leads to the possible emergence of toxicity (disorientation and aggression). Mefloquine may antagonize the anticonvulsant effect of carbamazepine. Ritonavir, a protease inhibitor, may cause toxicity by raising carbamazepine plasma levels. 

Stuer et al. [46] evaluated the presence of the 25 most used pharmaceuticals in the primary health sector in Denmark (e.g., paracetamol, acetyl salicylic acid, diazepam, and ibuprofen). They compared PECs with experimental determinations and they conclude that measured concentrations were in general within a factor of 2-5 of PECs. Carballa et al. [45] also determined PECs for pharmaceuticals (17), musk fragrances (2) and hormones (2) in sewage sludge matrix. For that purpose they used three different approaches (1) extrapolation of the per capita use in Europe to the number of Spanish inhabitants for musk fragrances (2) annual prescription items multiplied by the average daily dose for pharmaceuticals and (3) excretion rates of different groups of population for hormones. They indicated that these PECs fitted with the measured values for half of them (carbamazepine, diazepam, ibuprofen, naproxen, diclofenac, sulfamethoxazole, roxithromycin, erythromycin, and 17a-ethiny I e strad iol). 

Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or repeated courses are prescribed. The hepatitis is characterized by fever, enlarged and tender liver, hyperbilirubinemia, dark urine, eosinophilia, elevated serum bilirubin, and elevated transaminase levels. Hepatitis has been associated with the estolate salt of erythromycin but not with other formulations. Although the hepatitis usually occurs 10 to 20 days after the initiation of therapy, it can occur within hours in a patient who has had such a reaction in the past. The hepatitis is believed to be the result of both a hepatotoxic effect and a hypersensitivity reaction this latter effect is reversible on withdrawal of the drug. Erythromycin and derivatives induce hepatic microsomal enzymes and interfere with the actions of various drugs, including theophylline and carbamazepine. 

Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug s metabolism by CYP3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John s wort, and certain anticonvulsants (e.g., phenytoin, phenobarbital, and carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone)... 

Cardiac depressant effects may occur when verapamil or diltiazem is combined with a (p-adrenoceptor antagonoist or a cardiac glycoside. Nifedipine and verapamil are metabolised by cytochrome P-450 3A4. Inhibitors of this enzyme, e.g. HIV-protease inhibitors, cimetidine, fluoxetine, ketoconazole, erythromycin, will increase plasma levels and the dose should be carefully monitored. Conversely, enzyme inducers, e.g. carbamazepine, rifampicin, phenytoin, will decrease their plasma concentrations. 

Each Member State has to evaluate its own water quahty, identify why some areas do not reach the required standard, and then implement improvement plans. If a pharmaceutical residue is perceived to be contributing to the poor water quahty it is probable that an environmental quahty standard will be set for it. Comphance with this standard will then be needed, and this can only be accomplished by improving wastewater treatment or restricting sales. Draft standards have aheady been set in Germany for carbamazepine (0.5 pgL" ), diclofenac (0.1 ig I. ), erythromycin (0.02pgL ), ibuprofen (7.1 pg I, ), and metoprolol (7.3pgL ) [31], and in the United Kingdom for 17a-ethinyl estradiol (0.0001 pgL ). 

Metabolism Erythromycin is extensively metabolized and is known to inhibit the oxidation of a number of drugs through its interaction with the cytochrome P-450 system (see p. 14). Clarithromycin is oxidized to the 14-hydroxy derivative, which retains antibiotic activity interference with the metabolism of drugs such as theophylline and carbamazepine has been reported. Azithromycin does not undergo metabolism. 

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

Among drugs considered to be absorbed more quickly with food are carbamazepine, phenytoin, diazepam, dicoumarol, erythromycin (contentious), griseofulvin, hydralazine, hydrochlorothiazide, lithium citrate, labetalol, propranolol, metoprolol, nitrofurantoin, propoxyphene and spironolactone,... 

Interactions. Erythromycin and the other macro-lides are enzyme inhibitors and interfere with the metabolic inactivation of some drugs, e.g. warfarin, carbamazepine, theophylline, disopyramide, increasing their effects. Reduced inactivation of terfena-dine may lead to serious cardiac arrhythmias, and of ergot alkaloids may cause ergotism. 

Special attention is needed when new medications are prescribed to CSA-treated patients. CSA is extensively metabolized by the cytochrome P450 hver microsomal enzyme system [2, 3], and consequently drugs that interfere with this pathway can cause important changes in CSA blood levels (Table 3). Compounds inhibiting P450 enzymes, such as ketoconazole, erythromycin, verapamil, and diltiazem increase concentration of parent CSA and may cause acute nephrotoxicity. On the other hand, drugs that increase P450 enzyme activity, such as phenobarbital, carbamazepine and... 

Clinically important, potentially hazardous interactions with antihistamines, azole antifungals, benzodiazepines, carbamazepine, cimetidine, delavirdine, diazepam, erythromycin, HIV protease inhibitors, ketorolac, macrolide antibiotics, neuroleptics, phenobarbital, phenytoin, rifampin, ritonavir... 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, dexamethasone, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifampicin, ritonavir, saquinavir, St John s wort... 

Clinically important, potentially hazardous interactions with alfuzosin, amiodarone, aprepitant, carbamazepine, celiprolol, corticosteroids, cyclosporine, epirubicin, erythromycin, mistletoe, moricizine, oxprenolol, ranolazine, simvastatin, sulpiride... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

Clinically important, potentially hazardous interactions with aminophylline, aspirin, carbamazepine, clarithromycin, cyclosporine, daclizumab, erythromycin, itraconazole, ketoconazole, live vaccines, oral contraceptives, phenobarbital, rifampicin, rifampin, troleandomycin, warfarin... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Clinically important, potentially hazardous interactions with aprepitant, astemizole, carbamazepine, colchicine, cyclosporine, dihydroergotamine, ergot alkaloids, ergotamine, erythromycin, fluoxetine, fluvoxamine, methylprednisolone, methysergide, oral contraceptives, paroxetine, pimozide, prednisolone, rifampicin, sertraline, solifenacin, terfenadine, warfarin... 

Clinically important, potentially hazardous interactions with acebutolol, amiodarone, aspirin, atenolol, atorvastatin, betaxolol, carbamazepine, carteolol, celiprolol, donidine, dabigatran, dantrolene, digoxin, dofetilide, epirubicin, eplerenone, erythromycin, esmolol, eucalyptus, everolimus, lovastatin, metoprolol, mistletoe, nadolol, oxprenolol, penbutolol, pindolol, propranolol, quinidine, ranolazine, sibutramine, simvastatin, timolol, trabectedin... 

Co-admuiistration of erythromycin, phenytoin, or valproic acid increases the rate of metabolism of carbamazepine, reducing the blood concentration. Itraconazole and grapefruit juice interfere with CyP 3A4, increasing carbamazepine levels. 

Clearance of quinidine depends on CyP 3A4. Induction of this system by drugs such as carbamazepine, phenytoin, and St. John s Wort leads to enhanced clearance of quinidine. Diminished organ perfusion, CyP 3A4 inhibition by grapefruit juice or erythromycin, or co-administration with protease inhibitors results in decreased clearance. Quinidine itself has been reported to dilate peripheral blood vessels, resulting in mild to moderate hypotension and reduced clearance over the short term. Quinidine affects the rate of clearance of digoxin, Quinidine is analyzed by either HPLC or immunoassay. Fluorescence techniques should be considered obsolete. 

After single-dose administration, the mean bioavailability of quetiapine is 9% with significant interindividual variation. If a CYP 3A4 inhibitor (e.g., cimetidine, ketoconazole, nefazodone, grapefruit juice, or erythromycin) is added to quetiapine, increased side effects (e.g., sedation or orthostasis) may occur. Fluoxetine may also decrease clearance of a medication such as quetiapine metabolized through CYP 3A4. However, with fluoxetine, it is the long-acting metabolite norfluoxetine, and not fluoxetine, that is the primary inhibitor of 3 A4 metabolism. If an enzyme inducer such as carbamazepine or St. lohn s wort is added to quetiapine, then decreased antipsychotic effects may occur. ... 

Because of the risk of seizures with higher clozapine tissue concentrations, inhibition interactions with clozapine are potentially significant. In particular, fluvoxamine has been reported to increase clozapine serum concentrations by an average of two- to threefold and up to fivefold. Fluoxetine and erythromycin may increase clozapine serum concentrations in some patients, but to a lesser degree. Mean clozapine serum concentrations are reported to be 32% lower in smokers compared with nonsmokers." Carbamazepine may also induce clozapine metabolism and lead to lower serum concentrations. ... 

Carbamazepine is metabolized to an active 10,11-epoxide metabolite, thus medications that inhibit 3A4 isoenzymes may result in carbamazepine toxicity (e.g., cimetidine, dUtiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefa-zodone, propoxyphene, and verapamil). " When carbamazepine is combined with valproate, the carbamazepine dose should be reduced because valproate displaces carbamazepine from protein binding sites, thus increasing free levels." Combining clozapine and carbamazepine is not recommended because of the possibdity of bone marrow suppression with both agents. ... 

STPs are found to be the major contributor of pharmaceuticals in the Ebro River water. Compounds more frequently detected in the Ebro River basin were analgesics (diclofenac, naproxen, ibuprofen), lipid regulators (gemfibrozil, bezafibrate), antibiotics (azythromycin, trimethoprim, erythromycin, sulfamethoxazole), the antiepileptic carbamazepine, the antihistaminic ranitidine, and the 6-blockers atenolol and sotalol, which are the ones of major consumption in Spain as well as the ones excreted at higher percentages as parent drugs. Concentrations detected in both waste and surface waters are from 100 to 1000 times lower than the levels reported to cause acute toxicity. However, with respect to chronic effects, for some of the most ubiquitous compounds the margin of safety is narrow. As a wide spectrum of pharmaceuticals has been detected in natural waters, effects of mixtures should also be taken into account. 

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

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