Azithromycin adverse effects

The increase in azithromycin levels with nelfinavir is likely to be of clinical significance, and, although the outcome is presumed to be positive, this has yet to be assessed in practice. If concurrent use is necessary, monitor for azithromycin adverse effects. Single doses of azithromycin did not affect the pharmacokinetics of nelfinavir or indinavir, and the manufacturers of a combination product of lopinavir/ritonavir do not expect a clinically significant interaction with azithromycin. ... 

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. 

Long to, and higher tissue concentrations allow qd dosing however, the improved antimicrobial activity against Haemophilus influenzae and lower incidence of G1 adverse effects have not been realized with this agent azithromycin probably best choice pending further comparisons... 

AZITHROMYCIN PROTEASE INHIBITORS Risk of t adverse effects of azithromycin with nelfinavir Possibly involves altered P-gp transport Watch for signs of azithromycin toxicity... 

Two other agents show promise in treatment of ocular toxoplasmosis. Atovaquone, primarily used for mild to moderate episodes of Pneumocystis carinii pneumonia, has been effective in small series of patients with toxoplasmosis. It appears to have activity against both tachy-zoites and tissue cysts. More recent studies on atovaquone in toxoplasmosis are limited to murine models, and no further reports on this drug therapy in humans have been published. Azithromycin, a macrolide antibiotic, is efficacious against T. gondii and can also kill tissue cysts. A randomized study of 46 patients compared the combinations of azithromycin plus pyrimethamine versus pyrimethamine plus sulfadiazine in treatment of ocular toxoplasmosis efficacy was similar, but the azithromycin/ pyrimethamine regimen caused less adverse effects. 

In 3995 patients who took azithromycin 1.5 g in divided doses over 5 days or who took 1 g as a single dose for urethritis/cervicitis adverse events occurred in 12% (1). In patients over 65 years the rate was 9.3%, and in children under 14 years of age it was 5.4%. The most common adverse effects were gastrointestinal (9.6%) central nervous system and peripheral nervous system effects were reported in 1.3%. Overall, 59% of the adverse events were considered mild, 34% moderate, and only 6% severe, involving mainly the gastrointestinal tract. Adverse events resulted in withdrawal in 0.7% of patients, lower than the rate reported with other macro-lides. Treatment-related rises in liver enzymes were uncommon (under 2%), as was leukopenia (1.1-1.5%). 

Phase II/III clinical trials in the USA have yielded data on 1928 children aged 6 months to 15 years who took azithromycin for infections that included acute otitis media n — 1150) and streptococcal pharyngitis n — 754) (2). Most took a 5-day course of azithromycin (5-12 mg/kg/day). There were adverse effects in 190 patients (9.9%) diarrhea (3.1%), vomiting (2.5%), abdominal pain (1.9%), loose stools (1%), and rash (2.5%). In three comparisons with co-amoxiclav, the overall incidence of adverse effects was significantly lower with azithromycin (7.7 versus 29%), with withdrawal rates of 0.3 versus 3.6%. However, the incidence of adverse effects was significantly greater with azithromycin than with penicilhn V in comparisons in patients with streptococcal pharyngitis (13 versus 6.7%). In conclusion, it appears that the safety and tolerability of azithromycin is similar in children and adults. 

Compared with tetracycline, azithromycin had a favorable short-term effect on childhood morbidity in a mass trial for trachoma in rural Gambian villages, and adverse effects were limited (13). 

Treatment of facial comedonic and papulopustular acne with azithromycin (500 mg/day for 4 days in four cycles every 10 days) may be at least as effective as minocycline (100 mg/day for 6 weeks). Both were well tolerated and mild adverse effects were reported in 10% of patients given azithromycin and 12% of those given minocycline (14). 

Gastrointestinal symptoms were the most common adverse effects reported in a trial of azithromycin in disseminated Mycobacterium avium complex in 62 patients with AIDS (30). Erythromycin is a motilin receptor agonist (31-33). This mechanism may be at least partly responsible for the gastrointestinal adverse effects of macrolides. Azithromycin may act on gastrointestinal motility in a similar way to erythromycin, as it produces a significant increase in postprandial antral motility (34). 

In two randomized trials in pregnant women with cervical Chlamydia trachomatis infection, women were randomized to oral amoxicillin 500 mg tds for 7 days or oral azithromycin 1 g in a single dose (42,43). The two drugs had similar efficacy. Adverse effects were common in both groups 40% of those who took azithromycin reported moderate to severe gastrointestinal adverse effects compared with 17% of those who took amoxicillin. 

In a prospective, open, randomized trial clindamycin (600 mg tds) and quinine (650 mg tds) were compared with atovaquone (750 mg bd) plus azithromycin (500 mg on day 1 followed by 250 mg/day) in 58 patients with non-life-threatening babesiosis (3). Bacterial response was complete 3 months after the end of treatment. Adverse effects were reported by 72% of those who received clindamycin and quinine compared with 15% of those who received atovaquone and azithromycin. The most common adverse effects with clindamycin and quinine were tinnitus (39%), diarrhea (33%), and impaired hearing (28%) the symptoms had resolved in 73% of the patients assigned to clindamycin/quinine 3 months after the start of therapy and in 100% after 6 months. 

The gastrointestinal adverse effects are the most common untoward effects of the macrolides (Table 2). Nausea and vomiting associated with abdominal pain and occasionally diarrhea can be minor and transitory or, in a small percentage of patients, become severe enough to result in premature withdrawal. The rate of these adverse effects varies among the different antibiotics. In general, newer macrolides, such as azithromycin, clarithromycin, or roxithromycin, are better tolerated and cause fewer adverse effects than erythromycin. 

Erythromycin can cause two different types of liver damage (36,37), benign increases in serum transaminases, which may or may not recur on rechallenge, and cholestatic hepatitis. Reports of intrahepatic cholestasis with azithromycin (38), clarithromycin (39,40), and josamycin (41) suggest that the newer macrolides are not free of this adverse effect, although the relative risks compared with erythromycin are unclear. Similar involvement of the liver has been seen with the ester of triacetyloleandomycin, but not with the unesterified antibiotic. 

In a prospective, randomized, open, multicenter trial of pyrimethamine -I- azithromycin versus pyrimethamine + snlfadiazine for the treatment of ocular toxoplasmosis in 46 patients with sight-threatening ocular toxoplasmosis, the two regimens had similar efficacy however, the adverse effects were significantly less common and severe with pyrimethamine + azithromycin (2). 

In a multicenter study from the National Institute of Allergy and Infectious Diseases in the USA, azithromycin (600 mg/day) plus rifabutin (300 mg/day) was poorly tolerated by 31 patients with or without HIV infection (14). Gastrointestinal symptoms and neutropenia were the major adverse effects. There was no significant pharmacokinetic interaction between the two drugs. 

The macrolides (e.g., erythromycin, clarithromycin, and azithromycin) are translocation inhibitors. Their spectrums of activity, clinical uses, biodisposition, and adverse effects are considered. Clindamycin is not a macrolide but shares many of their properties. 

Not fully established. An in vitro study using human liver microsomes indicated that erythromycin inhibits the metabolism (mono-A-dealkylation) of disopyramide which, in vivo, would be expected to reduce its loss from the body and increase its serum levels. Clarithromycin and azithromycin probably do the same. The increased serum levels of disopyramide can result in adverse effects such as QT prolongation and torsade de pointes, and may result in enhanced insulin secretion and hypoglycaemia. - Both intravenous erythromycin and clarithromycin" alone have been associated with prolongation of the QT interval and torsade de pointes. Therefore, disopyramide and macrolides may have additive effects on the QT interval in addition to the pharmacokinetic interaction. 

In an analysis of the safety data from clinical studies of azithromycin, there was no evidenee that the plasma levels of theophylline were affeeted in patients given both drugs. Similarly, no adverse effects were reported in another elinieal study of patients taking azithromyein and theophylline. Azithromyein 250 mg twiee daily did not affeet the elearanee or serum levels of theophylline in patients with asthma. However, a 68-year-old man had a marked but transient fall in his serum theophylline level when azithromyein was withdrawn, and this was eonfirmed on reehal-lenge. The same authors eondueted a study in 4 healthy subjeets given azithromyein 500 mg on day 1 then 250 mg daily for 4 days and sustained-release theophylline 200 mg twiee daily. Theophylline levels were slightly elevated during the use of azithromyein, and a transient drop oeeurred 5 days after azithromyein was stopped. ... 

Li H, Liu DH, Chen LL, Zhao Q, Yu YZ, Ding JJ, et al. Meta-analysis of the adverse effects of long-term azithromycin use in patients with... 

In a multicenter, parallel-group, double-bhnd trial in 420 evaluable patients aged 6 months to 16 years with community-acquired pneumonia, the therapeutic effect of azithromycin (once-daily for 5 days) was similar to that of co-amoxiclav in children under 5 years and to that of erythromycin tds for 10 days. Treatment-related adverse events occurred in 11% of those given azithromycin and 31% in the comparator group (8). 

In general, erythromycin causes adverse G1 effects in the highest number of patients (21 percent). Clarithromycin causes significantly less (10 percent of patients experience adverse G1 effects), followed by azithromycin (5 percent of patients). 

Macrolides antibiotics have some side effects that adversely affect the patient. The most common side effects are nausea, vomiting, stomach pain, and cramps. These occur with azithromycin, clarithromycin, erythromycin, and dirithromycin. Troleandomycin causes stomach cramps and discomfort. 

There is a case of torsade de pointes possibly due to spiramycin with the sedating antihistamine mequitazine. The situation with erythromycin and loratadine is unclear as one study found that the combination caused a very slight increase in QT interval. Both azithromycin and erythromycin raise fexofenadine levels, but this had no effect on the QT interval, or on adverse events. Azelastine, cetirizine, desloratadine, and intranasal levocabastine seem to be free of clinically relevant interactions with macrolides. 

Fexofenadine levels are raised by both azithromycin and erythromycin but because this does not result in adverse cardiac effects concurrent use is considered safe. Azelastine, cetirizine (and therefore probably its isomer levocetirizine) desloratadine and levocabastine seem to be free from clinically significant pharmacokinetic interactions, and have no cardiac effects, and so may therefore provide suitable alternatives if a non-sedating antihistamine is needed in a patient taking macrolides. 

McLeod M, Barber N, Franklin BD (2015) Facilitators and barriers to safe medication administration to hospital inpatients a mixed methods study of nurses Medication Administration Processes and Systems (the MAPS Study). PLoS One 10 e0128958 McMuUan BJ, Mostaghim M (2015) Prescribing azithromycin. Aust Prescr 38 87-89 Mehrzad R, Barza M (2015) Weighing the adverse cardiac effects of fluoroquinolones a risk perspective. J Clin Pharmacol 55 1198-1206... 

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