Using diurnal intraocular pressure fluctuation to assess the efficacy of fixed-combination latanoprost/timolol versus latanoprost or timolol monotherapy.

AIM: To evaluate differences in diurnal intraocular pressure (IOP) fluctuation in glaucoma/ocular hypertension patients treated with once-daily fixed-combination latanoprost/timolol, once-daily latanoprost or twice-daily timolol. METHODS: In two 6-month, double-masked, parallel-group studies, patients received run-in timolol (2-4 weeks) and randomised (1:1:1) to therapy. IOP was measured three times/day at baseline and weeks 2, 13 and 26. In posthoc analyses, diurnal IOP fluctuation = highest daily IOP-lowest daily IOP at baseline and week 26. Fluctuation also was dichotomised: high (>6 mm Hg), low (< or =6 mm Hg). RESULTS: 854 patients were randomised (fixed combination = 278; latanoprost = 287; timolol = 289). Diurnal fluctuation was significantly reduced from baseline to week 26 with the fixed combination (p = 0.002) but not with latanoprost or timolol monotherapy (p = 0.601; p = 0.097). Relative to baseline, the percentage with high diurnal IOP fluctuation at week 26 was reduced by 48% with fixed combination but increased 13% with latanoprost and 48% with timolol. Changes in IOP fluctuation and in mean IOP were significantly correlated for the monotherapies but not the fixed combination. CONCLUSIONS: Fixed-combination latanoprost/timolol results in lower diurnal IOP fluctuation and significantly fewer patients with a high fluctuation than treatment with latanoprost or timolol monotherapy. The fixed combination may have an independent effect on reducing IOP fluctuation in addition to lowering IOP.

Efficacy and safety of fixed combinations of latanoprost/timolol and dorzolamide/timolol in open-angle glaucoma or ocular hypertension.

AIMS: To compare intraocular pressure (IOP) reductions with fixed-combination (FC) latanoprost/timolol once daily in the evening vsFC dorzolamide/timolol twice daily. METHODS: This evaluator-masked, multicentre, controlled clinical trial randomized subjects with primary open-angle glaucoma or ocular hypertension with IOP insufficiently responsive to beta-blocker therapy (screening IOP>21 and <37 mm Hg) to FC latanoprost-timolol (N=135) or FC dorzolamide/timolol (N=135). At screening, baseline, and after 4 and 12 weeks of therapy, IOP was measured three times at 0800, 1200, and 1600 hours. Adverse events were recorded at each visit. The primary efficacy end point was whether either FC could be shown to be inferior to the other with respect to change in mean daytime IOP from baseline to week 12. RESULTS: Mean daytime IOP levels were similar at baseline. Mean reductions in daytime IOP from baseline to week 12 were -9.7 mm Hg for FC latanoprost-timolol and -9.5 mm Hg for FC dorzolamide/timolol. The difference between FC latanoprost/timolol-FC dorzolamide-timolol was -0.2 mm Hg (95% confidence interval (CI), -0.8 to -0.4 mm Hg). The upper bound of the 95% CI was <1.5 mm Hg, indicating that neither FC is inferior to the other. However, a significantly greater percentage of subjects treated with FC latanoprost/timolol achieved IOP levels

Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin.

OBJECTIVE: To describe two cases of rhabdomyolysis in patients taking lovastatin that were precipitated by the use of the newer macrolide antibiotics clarithromycin and azithromycin. CASE SUMMARIES: In each case, the patients were treated over 5 years with lovastatin and developed rhabdomyolysis that coincided with the completion of a prescribed regimen of a newer macrolide antibiotic. Following intravenous hydration and administration of bicarbonate, the patients' condition resolved without permanent' sequelae. DISCUSSION: Rhabdomyolysis is a clinical syndrome resulting from the destruction of skeletal muscle that may progress to renal failure Several drugs have been associated with rhabdomyolysis, including lovastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor. Erythromycin is a macrolide antibiotic that may increase the risk of lovastatin-induced rhabdomyolysis. To our knowledge, these cases are the first published reports of lovastatin-induced rhabdomyolysis associated with azithromycin and clarithromycin. CONCLUSIONS: The risk of drug-induced rhabdomyolysis due to the potential interaction between lovastatin and azithromycin or clarithromycin should be considered before the concomitant use of these agents.