Rates Of Gastrointestinal Side Effects Research Articles

Tirzepatide, A New Antidiabetic Drug with Change in the Treatment of Patients with Type 2 Diabetes

Mounjaro® (tirzepatide) was approved by the U.S. Food and Drug Administration for type 2 diabetes treatment in August 2022. Tirzepatide, a synthetic peptide consisting of 39 amino acids, is a dual GLP-1 (glucagon-like peptide-1)/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. Tirzepatide showed marked reductions in glycated hemoglobin and body weight in the SURPASS study among participants with type 2 diabetes that surpassed existing diabetes drugs. Other benefits included blood pressure reduction and lipid lowering effects. On meta-analysis and post-hoc analysis, tirzepatide did not increase the risk of major cardiovascular events and is expected to have cardiovascular benefits in future studies. In addition, it showed a protective effect on the kidney by slowing the rate of renal function decline and reducing new-onset macroalbuminuria. However, the fact that it is an injectable drug, the cost of the drug, and the high rate of gastrointestinal side effects are disadvantages to tirzepatide. Considering the superior degree of glucose reduction and weight reduction observed in tirzepatide clinical trials compared to clinical trials of other anti-diabetic drugs, we expect tirzepatide to bring about a paradigm shift in the treatment of obese type 2 diabetes patients.

Trial of restarting and tolerating metformin (TreatMet).

This randomized, double-blind, placebo-controlled, n-of-1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow-up or were non-adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05 ) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.

Cervical Cancer with Intermediate Risk Factors: Is there a Role for Adjuvant Radiotherapy? A Systematic Review and a Meta-Analysis

Background: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. Material and Methods: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. Results: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28–0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03–3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). Conclusions: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Comparison of efficacy and toxicity between nedaplatin and cisplatin in treating malignant pleural effusion.

ObjectiveTo evaluate the efficacy and safety of nedaplatin versus cisplatin in treating malignant pleural effusion (MPE) caused by cancers.MethodsThe clinical data of 219 MPE patients treated from January 2013 to December 2016 were retrospectively reviewed. Intrapleural infusion with nedaplatin 80 mg/m2 (n=110) or with cisplatin 40 mg/m2 (n=109) were used as the treatment.ResultsThere was no significant difference in the overall response rate between the nedaplatin group (62.73%) and the cisplatin group (54.13%) (P=0.154). The nedaplatin group had significantly lower rates of gastrointestinal side effects and significantly less incidence of increased serum creatinine levels in comparison with the cisplatin group. The overall rate of toxicity in the nedaplatin group (40.00%) was significantly lower than in the cisplatin group (78.90%) (P⩽0.001).ConclusionThe efficacy of pleural perfusion with nedaplatin is noninferior to cisplatin in treating malignancy-induced MPE. Nedaplatin is associated with less toxicity in comparison with cisplatin.

Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis

BackgroundThere are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood–brain barrier, with potential salutary effects in progressive multiple sclerosis.MethodsWe enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis.ResultsOf 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was −0.0010 per year with ibudilast and −0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.ConclusionsIn a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942.)

A Comparison of Two Dosing Regimens of ASA Following Total Hip and Knee Arthroplasties

BackgroundThe purpose of this study was to compare short-term side effects of aspirin (ASA) 325 mg vs ASA 81 mg orally twice daily (PO BID) when used as thromboembolic prophylaxis following primary total joint arthroplasty. MethodsA 1-year prospective cohort study was performed on 643 primary unilateral total joint arthroplasty patients operated on by a single surgeon. Two hundred eighty-two patients were administered ASA 325 mg PO BID and 361 patients were administered ASA 81 mg PO BID for 1 month. A questionnaire assessing the side effects of ASA intake was administered 1 month postoperatively. ResultsThe overall rate of gastrointestinal side effects (GI upset and nausea) was 1.9%, but ASA 325 mg had a higher rate 9/282 (3.2%) than ASA 81 mg 3/361 (0.8%), P = .04. Overall GI bleeding was 0.9%, with 2/282 (0.7%) in the ASA 325 mg group, vs 4/361 (1.1%) in the ASA 81 mg group, P = .70. One patient in the ASA 81 mg group (0.3%) developed a deep vein thrombosis. No patient developed pulmonary embolism, periprosthetic joint infection, tinnitus, wheezing and/or shortness of breath, chest pain, or headaches. In the ASA 325 mg group, 9/282 (3.2%) discontinued ASA and in the ASA 81 mg group, 8/361 (2.2%) discontinued ASA, P = .47. Four patients in the ASA 325 group (1.4%) changed to ASA 81 mg. ConclusionASA 81 mg is associated with significantly less GI distress and nausea compared with ASA 325 mg. GI bleeding was equally prevalent between the 2 dosing regimens, so patients need to be informed of this risk regardless of the ASA dose.

Alzheimer's Symptomatic Drug Set to Test as Donepezil Combo

BARCELONA — RVT-101, a novel small molecule that increases acetylcholine release, is poised for what its developers say could be its pivotal trial for U.S. approval. The MINDSET study will examine the effect of the 5-HT6 receptor antagonist RVT-101, which will be given in conjunction with donepezil. As an acetylcholine booster, RVT-101 would not be a disease-modifying therapy. And like other symptomatic drugs, it would not alter the trajectory of Alzheimer's disease. Launched last month, MINDSET will be conducted in North America, South America, Europe, and Asia. The study investigators want to enroll least 1,000 patients with mild to moderate Alzheimer's disease who are on stable doses of donepezil, Lawrence Friedhoff, MD, PhD, said at the Clinical Trials on Alzheimer's Disease conference. Axovant Sciences' RVT-101, formerly developed as SB742457 by GlaxoSmithKline, has been investigated in 13 studies of both monotherapy and adjunctive therapy in more than 2,000 patients with Alzheimer's, said Dr. Friedhoff, chief development officer at Axovant Sciences. As monotherapy, it was ineffective, conferring no significant benefits on either cognition or function. The earlier study upon which MINDSET is modeled was a modestly successful phase IIb dose-ranging trial that comprised 684 patients. At 48 weeks, the combination of 35 mg SB742457 (RVT-101) and donepezil conferred about a 2-point benefit on the Alzheimer's Disease Assessment Scale–Cognitive (ADAS-cog) and the Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) over donepezil alone. Neither the 35-mg dose nor the 15-mg dose, which was also tested, conferred any benefit on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) test. “Regulators have told us that if our results are similar, then this study will be suitable for submission for approval,” Dr. Friedhoff said. “We have a reasonably high level of confidence that it will also be effective in this trial.” The 24-week MINDSET will randomize patients to their donepezil dosage plus either placebo or 35 mg RVT-101 daily. Coprimary endpoints are the ADAS-cog and the ADCS-ADL. The CDR-SB is not an endpoint in MINDSET, which Dr. Friedhoff noted was designed to maximize the chance of success. A 12-month open-label extension study focusing on long-term safety will follow the randomized trial. GSK ceased development of RVT-101 in 2010 without public explanation. However, a recent review of several of the GSK studies suggests that it simply didn't meet the studies' success criteria. Axovant was formed in 2014 to give RVT-101 a new shot as an add-on treatment. The combination makes sense, Dr. Friedhoff said. “It increases acetylcholine in the brain. We already know this is an effective way to treat Alzheimer's because our acetylcholinesterase inhibitors achieve this in a different way, by inhibiting the breakdown of acetylcholine,” Dr. Friedhoff explained. “It makes sense that they should work well together. It doesn't help much to increase the release if it's broken down quickly.” RVT-101 has an attractive safety profile, Dr. Friedhoff said. It had a low rate of gastrointestinal side effects (nausea, 2%; diarrhea, 5%) and was associated with very few falls in prior studies (about 3%). That relatively benign side effect profile is probably reflected in the study's large completer rate, Dr. Friedhoff said. The placebo and 35-mg dose had virtually identical completer rates of 88% and 89%, respectively. The dropout rates were low and similar in both groups. Axovant also aims to investigate RVT-101 in patients with Lewy body dementia, he added. The company expects to launch a phase IIb clinical study early next year. Dr. Friedhoff is an employee of Axovant Sciences. Michele G. Sullivan is with the Mid-Atlantic bureau of Frontline Medical News.

Utilisation des dérivés injectables du fer au cours de la maladie rénale chronique : intérêts, limites et conseils pour un bon usage

Iron deficiency is an important clinical concern in chronic kidney disease (CKD), giving rise to iron-deficiency anaemia, and various impaired cellular functions. Oral supplementation, in particular with ferrous salts, is associated with a high rate of gastro-intestinal side effects and is poorly absorbed, a problem that is avoided with intravenous (IV) irons. Recently, with the approval of the European Medicines Agency's Committee for Medicinal Products for Human Use, the French Agence nationale de sécurité du médicament et des produits de santé (ANSM) took adequate measures to minimize the risk of allergic reactions, by correction on the summary of intravenous iron products characteristics. All IV iron products should be prescribed, administered and injected, inside public or private hospitals exclusively, and a clinical follow-up after the infusion for at least 30 minutes is mandatory. The most stable intravenous iron complexes (low molecular weight iron dextran, ferric carboxymaltose, and iron isomaltoside 1000 [under agreement]) can be given in higher single doses and more rapidly than less recent preparations such as iron sucrose (originator or similars). Test doses are advisable for conventional low molecular weight iron dextrans, but are no more mandatory. Iron supplementation is recommended for all CKD patients with iron-deficiency anaemia and those who receive erythropoiesis-stimulating agents, whether or not they require dialysis. Intravenous iron is the preferred route of administration in haemodialysis patients, with randomized trials showing a significantly greater increase in haemoglobin levels for intravenous versus oral iron and a low rate of treatment-related adverse events during these trials. According ANSM, physicians should apply the product's label recommendations especially the posology. In the non-dialysis CKD population, the erythropoietic response is also significantly higher using intravenous versus oral iron, and tolerability is at least as good. Moreover in some non-dialysis patients, intravenous iron supplementation might avoid or at least delay the need for erythropoiesis-stimulating agents. Following the new ANSM's recommendations, we now have the ability to achieve iron stores replenishment correctly and conveniently in dialysis dependent and non-dialysis dependent CKD patients without compromising safety using the various pharmaceutical forms of iron products especially intravenous compounds.

Benefit-risk assessment of orlistat in the treatment of obesity.

Orlistat, an inhibitor of intestinal lipase, has been available for the treatment of obesity for nearly two decades. In conjunction with a hypocaloric diet, orlistat treatment results in a placebo-subtracted reduction in body weight of around 3 kg at 1 year, and increases the likelihood of achieving clinically significant (≥5%) weight loss by around 20%. Orlistat-induced weight loss also confers modest improvements in systolic and diastolic blood pressure, low-density lipoprotein (LDL) cholesterol, glycemic parameters, and progression to diabetes in people with impaired glucose tolerance. Overall, it has a good safety profile, and serious adverse events (including reports of severe kidney and liver injury) are rare. However, a high rate of gastrointestinal side effects limits adherence to treatment.

Donepezil 23 mg

Donepezil 10 mg/day has been a modestly successful therapeutic agent for the palliative treatment of Alzheimer disease dementia. In 2011, seeking greater efficacy and an extension of the Aricept brand, a 23-mg formulation of donepezil was introduced. A large-scale trial, organized by Eisai, the sponsor, failed to show superiority in their primary analyses of donepezil 23 mg/day in patients with moderate to severe Alzheimer disease dementia vs 10 mg, but the published report used post hoc analyses to claim "statistically significant benefits." There was greater than a 3 times higher rate of gastrointestinal side effects with 23 mg of donepezil compared to 10 mg. Thus, not only does donepezil 23 mg/day increase the likelihood of unacceptable gastrointestinal side effects, it provides no clinical benefits. Aricept 23 mg is about 10 times more costly per pill than donepezil 10 mg.

S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial.

S-Adenosyl-L-methionine (SAMe) is a dietary supplement commonly used to treat depression. SAMe facilitates dopamine and norepinephrine synthesis in the central nervous system. This study investigated the efficacy of SAMe for increasing tobacco abstinence among cigarette smokers. A randomized, blinded, placebo-controlled, three-arm, dose-ranging clinical trial was conducted. Subjects were randomly allocated to receive SAMe 1600 mg or 800 mg by mouth every day or a matching placebo for 8 weeks. All subjects received a behavioral smoking cessation intervention. Self-reported smoking abstinence was biochemically confirmed with exhaled-air carbon monoxide. Subjects in the study comprised 120 adults. One hundred and twenty (120) subjects with a mean age of 40.0±14.0 (SD) years were enrolled. Participants smoked an average of 19.6±8.6 cigarettes per day for 21±13.2 years. The study dropout rate was high (42.5%). By intention-to-treat analysis, no significant differences were observed in abstinence rates at 8 and 24 weeks between SAMe dose groups and placebo. SAMe did not attenuate withdrawal symptoms among abstinent subjects. Rates of gastrointestinal side-effects were higher with SAMe 1600 mg/d compared to placebo. SAMe did not increase smoking abstinence rates. Abstinence and tobacco withdrawal data from this clinical trial suggest that SAMe holds little promise for the treatment of tobacco dependence.

Journal of Diabetes NEWS

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Effects of metformin in adolescents with polycystic ovary syndrome undertaking lifestyle therapy: a pilot randomized double-blind study

Our small study does not support the addition of metformin to the lifestyle of adolescents. Although there are favorable trends toward hyperandrogenism with metformin, these must be balanced against the increased rate of gastrointestinal side effects. However, other treatments were associated with an improved quality of life.

Comparison of the therapeutic effects of pleural perfusion of NDP and cDDP in NSCLC patients with malignant pleural effusion

To compare the therapeutic effects of pleural perfusion of NDP and cDDP in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion, their quality of life and toxic side effects. Sixty-eight NSCLC patients with malignant pleural effusion after chest drainage were randomly divided into two groups according to the pathological types: 34 cases in the NDP (Group A) and cDDP groups (Group B), 34 cases each. They were treated with NDP (40 mg/m(2)) and dexamethasone (10 mg) dissolved in 40 ml normal saline, or cDDP (40 mg/m(2)) and dexamethasone (10 mg) dissolved in 40 ml of normal saline, respectively, through pleural perfusion weekly for 2-4 weeks. Routine and symptomatic treatment was used in all the patients. The therapeutic effects, life quality and toxic side effects were evaluated. The response rates of groups A and B were 88.23% and 61.7%, respectively, (P < 0.01). The rates of toxic side effects in groups A and B were 39.6% and 41.9%, respectively, (P > 0.05). However, the rates of gastrointestinal side effects of the two groups were 5% and 12.9%, respectively, (P < 0.05). The Karnofsky scores of group A were higher than that in group B (P < 0.05). The survival time of group A was significantly longer than that of group B. Pleural perfusion with NDP is a good treatment method with milder toxicity for patients with malignant pleural effusion caused by NSCLC.

Side Effects of Phytoestrogens: A Meta-analysis of Randomized Trials

Background Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown. Methods Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials. Results We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively ( P = .2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users ( P = .003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups. Conclusions Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.

Long term pharmacotherapy for obesity and overweight: updated meta-analysis

Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.Design Updated meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane controlled trials register,...

Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

Cardiovascular events (CVEs) are the leading cause of death in chronic hemodialysis patients. Results of trials in non-end-stage renal disease (ESRD) patients cannot be extrapolated to patients with ESRD. It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials. The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD. Eligible patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo (n=201) plus conventional therapy for 24 months. The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death, nonfatal stroke, heart failure, myocardial infarction, or revascularization). No significant benefit for fosinopril was observed in the intent to treat analysis (n=397) after adjusting for independent predictors of CVEs (RR=0.93, 95% confidence interval (CI) 0.68-1.26, P=0.35). The per protocol secondary supportive analysis (n=380) found a trend towards benefit for fosinopril (adjusted RR=0.79 (95% CI 0.59-1.1, P=0.099)). In the patients who were hypertensive at baseline, systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group. After adjustment for risk factors, trends were observed suggesting fosinopril may be associated with a lower risk of CVEs. These trends may have become statistically significant had the sample size been larger, and these findings warrant further study.

Preference and acceptability of oral versus vaginal administration of misoprostol in medical abortion with mifepristone

Objectives To compare the experience of pain, need of analgesic interventions, preference and acceptability in medical abortion up to 49 days of amenorrhea with mifepristone and orally versus vaginally administered misoprostol. Study Design Ninety-seven women were randomised to oral misoprostol, n = 48, or vaginal misoprostol, n = 49. On day 1 of the study, both the groups received 600 mg of mifepristone. On day 3 of the study, one group received 0.4 mg of misoprostol orally and the other group received 0.8 mg of misoprostol vaginally. Results Even though oral administration of misoprostol seemed to be associated with a higher rate of gastrointestinal side effects, women in both the groups showed a clear preference towards the oral route of administration. The willingness to administer the misoprostol at home was also higher among the women in the oral group, which may in part depend on a more positive/less negative experience of the abortion. Conclusion A majority of women prefer oral administration of misoprostol in early medical abortion.

Macrolides in the management of streptococcal pharyngitis/tonsillitis.

The most frequent bacterial cause of pharyngitis/tonsillitis, a common infection in children, is group A beta-hemolytic streptococci. Prevention of acute rheumatic fever is the principal goal of treatment, although antibiotic therapy may also relieve the signs and symptoms of infection, shorten the infective period and prevent suppurative complications. Penicillin is the drug of choice. Alternatives are required, however, for patients allergic to penicillin and may be needed if the rate of bacteriologic failure with penicillin observed during the past decade continues. Erythromycin is generally effective in this infection, but its use, especially in children, is complicated by the need for multiple daily doses, a lengthy treatment period and a high rate of gastrointestinal side effects. The newer macrolides clarithromycin and azithromycin offer lower rates of gastrointestinal complaints and more convenient dosing. Clarithromycin is recommended for twice daily and azithromycin for once daily administration. Because of its prolonged tissue half-life, the recommended duration of azithromycin therapy is 5 days, compared with 10 days for penicillin, erythromycin and clarithromycin. Newer macrolides are rational alternatives to erythromycin for streptococcal pharyngitis/tonsillitis in penicillin-allergic patients.

The role of azithromycin and clarithromycin in clinical practice.

Azithromycin and clarithromycin are the newest approved macrolide antibiotics. To review the pharmacology, microbiology, and clinical utility of these agents. These agents have distinct advantages over erythromycin, including an improved pharmacokinetic profile, less toxicity, and a wider spectrum of activity. They are approved for the treatment of respiratory tract infections and uncomplicated skin and skin-structure infections associated with specific organisms. Azithromycin is also indicated for the treatment of nongonococcal urethritis. In addition, these agents may be useful in the treatment of toxoplasmosis, mycobacterial disease, Lyme disease, and legionellosis. Clarithromycin and azithromycin have lower rates of gastrointestinal side effects than erythromycin. Although clarithromycin and azithromycin show promise in the treatment of some less common infections, they should be considered alternatives to conventional agents in the treatment of respiratory tract, skin, and skin-structure infections caused by the usual pathogens. The expense of these agents may be prohibitive for routine use.