Clarithromycin adverse effects

Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. 

In patients allergic to penicillin, a macrolide such as erythromycin or a first-generation cephalosporin such as cephalexin (if the reaction is nonimmunoglobulin E-mediated hypersensitivity) can be used. Newer mac-rolides such as azithromycin and clarithromycin are as effective as erythromycin and cause fewer GI adverse effects. 

There are a number of factors that limit the effectiveness of regimens designed to eradicate H. pylori. The first, antibiotic resistance, is seen with metronidazole and clarithromycin but has not been reported with bismuth, amoxicillin, or tetracycline. Second, mild adverse effects (eg, diarrhea, metallic taste, black stools) do occur in approximately 30% to 50% of patients. Therefore, shorter treatment periods in this group of patients may be better tolerated. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

The adverse effects that most frequently result in discontinuation of rifabutin include GI intolerance, rash, and neutropenia. Rifabutin levels will be increased with concurrent administration of fluconazole and clarithromycin, resulting in anterior uveitis, polymyalgia syndrome, and a yellowish-tan discoloration of the skin (pseudojaundice). Other adverse reactions are similar to those of rifampin, such as hepatitis, red-orange discoloration of body fluids, and drug interactions due to effects on the hepatic P450 cytochrome enzyme system. 

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

CALCIUM CHANNEL BLOCKERS MACROLIDES t plasma concentrations of felodipine when co-administered with erythromycin cases of adverse effects of verapamil (bradycardia and 1 BP) with both erythromycin and clarithromycin Erythromycin inhibits CYP3A4-mediated metabolism of felodipine and verapamil. Clarithromycin and erythromycin inhibit intestinal P-gp, which may t the bioavailability of verapamil Monitor PR and BP closely watch for bradycardia and 1 BP. Consider reducing the dose of calcium channel blocker during macrolide therapy... 

MODAFINIL 1. ANTIBIOTICS-clarithromycin, telithromycin 2. ANTIFUNGALS-itraconazole, ketoconazole 3. ANTIVIRALS-indinavir, nelfinavir, ritonavir, saquinavir t plasma concentrations of modafinil, with risk of adverse effects Due to inhibition of CYP3A4, which has a partial role in the metabolism of modafinil Be aware. Warn patients to report dose-related adverse effects, e.g. headache, anxiety... 

CLARITHROMYCIN, ERYTHROMYCIN VINCA ALKALOIDS -VINBLASTINE, VINCRISTINE, VINORELBINE t adverse effects of vinblastine and vincristine Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Monitor FBCs. Watch for early features of toxicity (pain, numbness, tingling in the fingers and toes, jaw pain, abdominal pain, constipation, ileus). Consider selecting an alternative drug... 

CLARITHROMYCIN NNRTIs 1. i efficacy of clarithromycin but t efficacy and adverse effects of the active metabolite 2. A rash occurs in 46% of patients when efavirenz is given with clarithromycin 1. Uncertain possibly due to altered CYP3A4-mediated metabolism 2. Uncertain 1. Clinical significance unknown no dose adjustment is recommended when clarithromycin is co-adminis-tered with nevirapine, but monitor LFTs and activity against Mycobacterium avium intracellulare complex closely 2. Consider alternatives to clarithromycin for patients on efavirenz... 

CLARITHROMYCIN, ERYTHROMYCIN PROTEASE INHIBITORS Possibly t adverse effects of macrolide with atazanavir, ritonavir (with or without lopinavir) and saquinavir Inhibition of CYP3A4- and possibly CYP1 A2-mediated metabolism. Altered transport via P-gp may be involved. Amprenavir and indinavir are also possibly t by erythromycin Consider alternatives unless there is Mycobacterium avium intracellulare infection if combined, 1 dose by 50% (75% in the presence of renal failure with a creatinine clearance of <30mL/min)... 

ERYTHROMYCIN H2 RECEPTOR BLOCKERS -CIMETIDINE t efficacy and adverse effects of erythromycin, including hearing loss t bioavailability Consider an alternative antibiotic, e.g. clarithromycin. Deafness was reversible with cessation of erythromycin... 

CLARITHROMYCIN PROTON PUMP INHIBITORS -OMEPRAZOLE t efficacy and adverse effects of both drugs t plasma concentration of both drugs No dose adjustment recommended. Interaction considered useful for Helicobacter pylori eradication... 

Macrolide antibiotics are contraindicated in patients with known hypersensitivity or intolerance to any macrolide. Because clarithromycin can have adverse effects on embryo-fetal development in animals, this drug should be avoided in pregnant women unless no other therapy is appropriate. Concurrent administration of the macrolides and astemizole or terfenadine can cause elected antihistamine levels, resulting in life-threatening cardiac arrhythmias, and should be avoided. 

In a multicenter, double-blind, randomized comparison of trovafloxacin 200 mg and clarithromycin 500 mg bd in 176 subjects with acute exacerbations of chronic bronchitis, the most common adverse effects of trovafloxacin were nausea (5%), dizziness (5%), vomiting (3%), and constipation (3%) (1). Because trovafloxacin is hepato-toxic, the list of appropriate indications has been limited to patients who have at least one of several specified infections, such as nosocomial pneumonia or complicated intra-abdominal infections that are serious and life- or limb-threatening in the physician s judgement. 

Mild gastrointestinal disturbances are common in patients taking chloramphenicol. In 51 children with Mediterranean spotted fever randomized for 7 days to either clarithromycin, 15 mg/kg/day orally in two divided doses, or chloramphenicol, 50 mg/kg/day orally in four divided doses, the two drugs were equally well tolerated and there were no major adverse effects there was vomiting in two patients treated with clarithromycin and in one treated with chloramphenicol (44). None of the patients required drug withdrawal. 

In a multicenter, double-blind, randomized comparison of trovafloxacin 200 mg and clarithromycin 500 mg bd in 176 subjects with acute exacerbations of chronic bronchitis, the most common adverse effects of clarithromycin were nausea (3%), diarrhea (4%), and taste disturbances (4%) (9). 

Clarithromycin (0.75-2 g/day), minocycline (200 mg/ day), and clofazimine (100 mg/day) for 15 months were investigated as treatment of MAC lung disease in 30 HIVnegative patients. Eight patients did not complete the study owing to deviations from protocol or adverse effects. Persistently negative cultures were found in 14 of the other patients. There were three cases of hepatic disturbances and three of ototoxicity, which required a reduction in clarithromycin dosage after a short interruption of treatment (10). 

Erjdhromycin acts as a motilin receptor agonist (27-29). This mechanism may be at least partly responsible for the gastrointestinal adverse effects of macrolides. Clarithromycin may act on gastrointestinal motility in a similar way. In dogs, clarithromycin caused contractions and discomfort, as did erythromycin (30). In healthy volunteers, oral clarithromycin 250 mg bd caused a statistically significant increase in the number of postprandial antral contractions and antral motility (31). A single oral dose of clarithromycin 3000 mg resulted in severe abdominal pain within 1 hour of administration in two patients (32). 

The effects of fluconazole and clarithromycin on the pharmacokinetics of rifabutin and 25-O-desacetylrifabu-tin have been studied in ten HIV-infected patients who were given rifabutin 300 mg qds in addition to fluconazole 200 mg qds and clarithromycin 500 mg qds (73). There was a 76% increase in the plasma AUC of rifabutin when either fluconazole or clarithromycin was given alone and a 152% increase when both drugs were given together. The authors concluded that patients should be monitored for adverse effects of rifabutin when it is co-administered with fluconazole or clarithromycin. 

The MACH-2 study has assessed the role of omeprazole in triple therapy in 539 patients with duodenal ulcers associated with H. pylori (3). The addition of omeprazole resulted in significantly higher eradication rates (over 90%) than antibiotics alone (amoxicillin plus clarithromycin about 25% clarithromycin plus metronidazole 70%), and reduced the impact of primary resistance to metronidazole. About one-third of the patients who took amoxicillin reported diarrhea/loose stools. The frequency of taste disturbance was dose-dependent with clarithromycin. Increased liver enzymes were more commonly reported in those taking metronidazole. The addition of omeprazole did not increase the frequency of reported adverse effects. 

The DU-MACH study assessed the efficacy of two omeprazole-based triple therapies (omeprazole, amoxicillin, clarithromycin versus omeprazole, metronidazole, clarithromycin) given for 1 week to 149 patients for eradicating H. pylori, healing duodenal ulcers, and preventing ulcer relapse over 6 months after treatment (4). Both regimens achieved high eradication rates (about 90%) and were well tolerated. Adverse effects were similar in the two groups, and included diarrhea, taste disturbance, headache, nausea, and dyspepsia. 

Ranitidine 300 mg bd and omeprazole 20 mg bd have been compared as components of triple therapies (combining them with either amoxicillin plus clarithromycin or amoxicillin plus metronidazole) in 320 patients with H. pylori (5). Omeprazole and ranitidine combined with two antibiotics for 1 week were equally effective in eradicating H. pylori. This result questions the role of profound acid suppression in eradication. There was no difference in the reported adverse effects, which included nausea, vomiting, diarrhea, metallic taste, skin rashes, and headache. 

In a similar study in 221 patients with peptic ulcer disease associated with H. pylori, rabeprazole has been compared with omeprazole and lansoprazole (combining them with amoxicillin plus clarithromycin for 1 week) (6). Rabeprazole was as effective as omeprazole and lansoprazole in eradicating H. pylori (84-88% each). There were no differences in reported adverse events. Common adverse effects were soft stools, glossitis, taste disturbances, and skin rashes. 

Dual therapy (omeprazole plus clarithromycin) for 2 weeks has been compared with triple therapy (omeprazole plus amoxicillin and clarithromycin) for 1 week in the eradication of H. pylori in 145 patients with duodenal nlcers (7). Triple therapy was significantly more effective in eradicating H. pylori (71 versus 48%). There were no significant differences in comphance or adverse effects. The most freqnent adverse effects were metallic taste and nansea in the dnal-therapy gronp and metalhc taste, mild abdominal pain, and diarrhea in the triple-therapy group. 

Sucralfate 1 g tds in combination with amoxicillin 500 mg tds and clarithromycin 400 mg bd for 2 weeks was as effective as a combination of lansoprazole 30 mg bd plus amoxicillin 500 mg tds and clarithromycin 400 mg bd for 2 weeks for H. pylori eradication in a randomized, multicenter trial in 150 patients (9). There was no significant difference in adverse effects between the two groups. Diarrhea, abdominal pain, glossitis, and taste disturbance were the adverse effects commonly reported. 

In an open trial, 7-day triple therapy with omeprazole 30 mg bd, amoxicillin 500 mg tds, and clarithromycin 400 mg bd was safe and effective in eradicating H. pylori in 12 of 13 patients undergoing hemodialysis (10). There were adverse effects in two patients (compared with three of 27 patients not undergoing hemodialysis) and treatment had to be discontinued in one, owing to severe nausea and vomiting. 

In a randomized, controlled trial in 120 patients supplementation with inactivated Lactobacillus acidophilus tds significantly improved the efficacy of a standard 7-day regimen with rabeprazole 20 mg bd, clarithromycin 250 mg tds, and amoxicillin 500 mg tds (12). There was no significant difference in adverse effects between the two groups. Those reported were abdominal pain, nausea, and diarrhea. 

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