Macrolide side effects

Macrolides are regarded as among the safest of antibiotics (496). The principal side effects, which ia some cases are sufftciendy severe to require cessation of the drug, are gastroiatestinal. 

For the topical treatment of some chronic inflammatory skin diseases (like atopic dermatitis) immunosuppressive macrolides (like TRL and pimecrolimus) that permeate the inflamed epidermis are of benefit for patients. Severe side effects comparable to those after systemic application of TRL in transplanted patients (see above) have not been observed so far. For the treatment of psoriasis vulgaris these drugs are less effective. The CD2 antagonist alefacept may be a suitable alternative to allergic reactions. 

Telithromycin 800 mg once daily x 5 days Not available Improved pneumococcal coverage over macrolides can cause blurred or double vision and difficulty focusing cost and other side effects similar to clarithromycin-azithromycin... 

Clarithromycin is a derivative of erythromycin (macrolide). Advantages over erythromycin include lower frequency of gastrointestinal side-effects and lower dosage frequency. Clarithromycin is administered every 12 hours. As with all macrolides it should be used with caution in patients who are at risk of developing QT interval prolongation caused either by electrolyte imbalances or the concomitant use of other drugs. 

Roxithromycin, clarithromycin, azithromycin and dirithromycin are more recently developed macrolides with similar antimicrobial activity to erythromycin. However they are better absorbed, have longer elimination half-lives and lower incidence of gastrointestinal side-effects. Azithromycin and... 

Pimecrolimus (SDZ ASM 981, Elidel) is another recently approved macrolide immunosuppressant that acts by inhibiting calcineurin and blocking the release of proinflammatory cytokines from T lymphocytes. The parent compound, ascomycin, was originally isolated from Streptomyces hygroscopicus var ascomyceticus. Like tacrolimus, pimecrolimus is approved for the topical treatment of moderate to severe atopic dermatitis that is refractory to other therapies. Transient local irritation is a common side effect. 

Amphotericin B (AmB) is a polyenic macrolide used in fungal infections and leishmaniasis, despite severe side effects (Figure 4.60). Fluorination of the macrolide skeleton has been performed using Selectfluor for F NMR studies on the mechanism of ion-channel formation in membranes by amphotericin B. ... 

Tacrolimus (previously known as FK506) is a macrolide antibiotic with immunosuppressive properties very similar to cyclosporin. It is more potent than cyclosporin but the side effects are similar. Tacrolimus is a very active immunosuppressive drug both in the prevention and treatment of liver and renal allograft rejection. It is especially valuable for small bowel transplantation. 

Rapamycin, also known as sirolimus, is a new macrolide antibiotic that interacts with cellcycle regulating proteins and inhibits cell division. The main side effects are thrombocytopenia and hyperlipidaemia. There is also evidence that it causes interstitial pneumonitis, which may resolve on withdrawing the drug or dose reduction. The drug is currently being assessed for combination therapy with tacrolimus or cyclosporin. 

Pharmacokinetics attd Pharmacology. Older macrolides such as erythromycin exhibit relatively low serum concentrations, short in vivo half-hves, highly variable oral absorption, and low oral bioavailability. Improvements in these pharmacokinetic parameters have been accomplished for newer derivatives. The principal side effects of macrolides aie gastrointestinal problems, such as pain, indigestion, diarrhea, nausea, and vomiting. 

Epigastric distress This side effect is common and can lead to poor patient compliance for erythromycin. The new macrolides seem to be better tolerated by the patient gastrointestinal problems are their most common side effects. 

All macrolides are regarded as relatively safe antibiotics whose principal side-effects are gastrointestinal disturbances ranging from mild upset to severe pain [281], Gastrointestinal motility in conscious dogs is not affected by 16-membered macrolides, in contrast to the substantial effects provoked by 14-membered macrolides [282-284]. These different effects on motility have recently been confirmed in clinical studies of miokamycin compared with several 14-membered macrolides [285, 286]. Less frequent side-effects such as hypersensitivity and cutaneous reactions have been mentioned [35, 287, 288]. 

A review of 16-membered macrolide antibiotics (Chapter 5) complements a survey of semi-synthetic erythromycins which appeared in Volume 30. Further work in this direction is expected to yield new antibiotics of greater efficiency and a lower level of side-effects. The antibacterial effects of silver have been known for a long time and are assessed in Chapter 7. 

Drug interactions Drugs utilizing the CYP2D6 (i.e., f luoxetine, cimetidine) or the CYP3A4 (i.e, macrolides, antiretrovirals) pathways may inhibit opioid metabolism and potentiate side effects. Drugs such as benzodiazepines and barbiturates should be used cautiously in combination with opioids, as they may potentiate respiratory depression or sedative effects. 

Polyene macrolides consist of a macrocyclic lactone, a polyene chromophore, and a polyhy-droxylated chain which often bears glycosidic residues. These antibiotics, e. g., amphotericin B (49) and nystatin Ai (50) (O Scheme 20), are used as potent antifungal antibiotics although they cause side effects such as nephrotoxicity, hemolytic anemia and electrolyte abnormalities [70]. 

The patient must be instructed to Provide their healthcare provider with a complete history of over-the-counter medications, prescribed medications, and herbal therapies to identify contraindications for macrolides. Explain that there might be a chance of hearing loss as an adverse side effect of macrolides. Monitor for adverse effects (see 13.21 Macrolide Antibiotics), and call the healthcare provider immediately if one is present. Macrolide Antibiotics Pregnancy Category B ... 

Freiberg, L. A., Klein, L., Hannick, S., Nellans, H. N., Fernandes, P. B., and Pemet, A. G. (1987). A-63075, a potent 14-membered macrolide with minimal gastrointestinal side-effects. Presented at 27th Intersci. Conf. Antimicrob. Agents Chemother (Oct. 4-7, New York). Abstr. No. 224. 

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