See also Incidence of Adverse Effects, above. The syndrome of inappropriate antidiuretic hormone secretion was associated with azithromycin treatment in a patient. Acute interstitial nephritis leading to irreversible renal failure has been reported in a patient who received azithromycin for 9 days. A later report described a patient who developed recurrent acute interstitial nephritis after courses of azithromycin.
Repeated exposure resulted in persistent renal damage; leucocytosis and eosinophilia were still present 1 year later. A syndrome characterised by eosinophilia, arthralgia, fever, and rash was associated with azithromycin or roxifhromycin treatment in a patient on separate occasions.
The original authors believed the condition represented the Churg-Strauss syndrome, although this was disputed in correspondence and attributed to the eosinophilia-myalgia syndrome. For a discussion of drug interactions of macrolide antibacterials, see Erythromycin. Giving azithromycin with antacids containing aluminium or magnesium salts can reduce the rate, but not the extent, of its absorption; azithromycin should be given at least 1 hour before or 2 hours after the antacid. Azithromycin serum concentrations are markedly increased when it is given with nelfinavir, but the clinical significance of this is uncertain.
US licensed product information for azithromycin states that dosage adjustment is not required although the patient should be closely monitored for adverse effects. As for Erythromycin. Azithromycin is less active than erythromycin against streptococci and staphylococci, but has greater activity than erythromycin in vitro against some Gram-negative organisms such as Haemophilus influenzae and Moraxella catarrhalis Branhamella catarrhalis , as well as having activity against some of the Enterobacteriaceae such as Escherichia coli and Salmonella and Shigella spp.
Azithromycin is also more active than erythromycin against Chlamydia trachomatis and Ureaplasma urealyticum, and some opportunistic mycobacteria, including Mycobacterium avium complex. It has activity against the protozoa Toxoplasma gondii and Plasmodium falciparum. Absorption from capsules, but not tablets or suspension, is reduced by food.
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Peak plasma concentrations occur 2 to 3 hours after an oral dose and 1 to 2 hours after intravenous dosage. However, azithromycin is extensively distributed into the tissues, and tissue concentrations subsequently remain much higher than those in the blood; in contrast to most other antibacterials, plasma concentrations are therefore of little value as a guide to efficacy.
High concentrations are taken up into white blood cells.
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There is little diffusion into the CSF when the meninges are not inflamed. Data from animal studies indicate that azithromycin crosses the placenta. Small amounts of azithromycin are demethylated in the liver, and it is excreted in bile mainly as unchanged drug and a number of inactive metabolites have also been detected. The terminal elimination half-life is about 68 hours. Azithromycin is a nitrogen-containing macrolide azalide with actions and uses similar to those of erythromycin. It is given in the treatment of respiratory-tract infections including otitis media , in skin and soft-tissue infections, and in uncomplicated genital infections.
Azithromycin may also be used for the prophylaxis, and as a component of regimens in the treatment, of Mycobacterium avium complex MAC infections. It is used in some countries for the prophylaxis of endocarditis in atrisk patients unable to take penicillin. It is also used in the management of trachoma and typhoid. For details of all these infections and their treatment, see under Choice of Antibacterial. Azithromycin has been tried in protozoal infections such as babesiosis below , crytosporidiosis, and toxoplasmosis.
It is given orally or by intravenous infusion usually as the dihydrate; doses are expressed in terms of the anhydrous substance.
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Azithromycin dihydrate mg is equivalent to about mg of anhydrous azithromycin. The capsule formulation should be given at least 1 hour before, or 2 hours after, meals. The usual oral adult dose of azithromycin is mg as a single dose daily for 3 days. Alternatively, an initial dose of mg may be followed by mg daily for a further 4 days. For uncomplicated genital infections caused by Chlamydia trachomatis and for chancroid, 1 g of azithromycin is given as a single dose. A single dose of 2 g has been given for uncomplicated gonorrhoea. For the treatment of granuloma inguinale, an initial dose of 1 g followed by mg daily may be given, or 1 g may be given once a week for at least 3 weeks, until all lesions have completely healed.
In the USA, a modified-release preparation given as an oral suspension is available. The product delivers a single dose of 2 g and should also be taken on an empty stomach.
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