Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis.

Background: Vaginal candidiasis (VC) is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial. Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge) and positive microscopic smear (pseudohyphae and/or yeast cells) were randomized to receive a single dose of either keto-fluco combination (n = 85) or fluconazole (n = 80), and returned for follow-up visit on day 8. Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture), while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture) and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement) in the keto-fluco arm (n = 60) was 98.3%, while that in the fluconazole group (n = 66) was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5%) and 2 patients in the fluconazole group (2/80 = 2.5%). Conclusion: The present study showed that the efficacy and safety of ketoconazole 100 mg and fluconazole 40 mg combination was not inferior compared to fluconazole 150 mg in single doses for the treatment of vaginal candidiasis.

The efficacy of Rhinos® SR on nasal resistance and nasal symptoms in patients with perennial allergic rhinitis : a randomized, double-blind, placebo-controlled study.

Rhinos® SR is a fixed combination of 5 mg loratadine and 60 mg pseudoephedrine immediate release and 60 mg pseudoephedrine sustained release. The present study was aimed to assess the efficacy of Rhinos® SR on nasal airway resistance (NAR) objectively using rhinomanometer and on nasal symptoms in patients with perennial allergic rhinitis (PAR) in a tropical country. This was a randomized, double-blind, parallel group study in 59 PAR patients who visited the ENT clinic at Dr. Soetomo General Hospital, Surabaya. Outpatients of both gender, having moderate to severe PAR for a minimal of 2 years, aged 12 years or older, with a total nasal symptom score (TNSS) > 6 and a nasal congestion score > 2, received Rhinos® SR or placebo twice daily for 7 days. The primary efficacy parameter was the decrease in the NAR values (measured by rhinomanometer on Day 1) of Rhinos® SR from those of placebo. The NAR values were calculated as the area under the curve (AUC) of NAR versus time. The secondary efficacy parameters were the percentage reduction of the clinical symptoms (nasal and nonnasal) evaluated by both the patient and the physician after 1 week use of Rhinos® SR or placebo. From 59 eligible patients, all completed this 1-week trial. For NAR values, after the baseline were considered as 100%, the AUC0-10 h were not significantly different between Rhinos® SR and placebo. However, as the pseudoephedrine reached its peak concentration, i.e. 2 hrs for the immediate release and 6 hrs for the sustained release, then AUC0-2 h and AUC0-6 h of Rhinos® SR were significantly lower compared to those of placebo. Total nasal symptom score (TNSS) evaluated by the patient (sum of the last 3 mornings) for Rhinos® SR decreased 33.0% from baseline (p < 0.001), for placebo decreased 21.9% from baseline (p = 0.002), but the decrease by Rhinos® SR was not significantly different from the decrease by placebo. TNSS evaluated by the physician, nasal congestion score (NCS) and total symptom score (TSS, total nasal and nonnasal), and even the individual symptom scores, evaluated by the patient and the physician, showed similar pattern, i.e. both Rhinos® SR and placebo decreased the symptoms significantly from baseline, and the decreases by Rhinos® SR were larger than the decreases by placebo, but the decreases by Rhinos® SR and placebo were not statistically different. No adverse event was found in this study. From the present study it was concluded that in patients with moderate to severe PAR in a tropical country, Rhinos® SR was effective in relieving nasal congestion by objective measurements of NAR. Rhinos® SR twice a day for 7 days was also effective in reducing the clinical symptoms of PAR although the reductions did not reach statistical significance compared to those by placebo, and was well tolerated.

Safety and tolerability of fluvastatin XL in the treatment of hyper-cholesterolemia : a postmarketing surveillance conducted in Indonesia.

Fluvastatin XL 80 mg tablet has been marketed in Indonesia since December 2002. This post-marketing surveillance (PMS) was conducted between May 2004 and April 2005 involving 98 general physicians to observe the safety and tolerability of fluvastatin XL 80 mg once daily at bedtime for 8 weeks in the treatment of outpatients with hypercholesterolemia. The efficacy of the drug in lowering LDL-cholesterol and other lipid parameters was also observed in daily clinical practice in this PMS. A total of 740 patients were eligible for safety analyses. There were 32 patients (4.32%) with 39 adverse events that were considered related to fluvastatin XL therapy. The most common adverse reactions were dizziness (2.03%), nausea (1.22%), and myalgia (0.68%). No serious adverse event (SAE) was found in this PMS, and no patient discontinued due to adverse event. According to physician’s global evaluation, the safety and tolerability of treatment was good in 91.9% of patients. For efficacy analyses, only 566 patients were eligible. At week 8, fluvastatin XL caused decreases in LDL-cholesterol (LDL-C), total cholesterol (TC) and triglyceride (TG) levels by 28.6%, 30.2% and 24.5%, respectively, and an increase in HDL-cholesterol (HDL-C) by 14.3%. In 74 patients with baseline TG > 300 mg/dL, the decrease in TG was 38.1% and the increase in HDL-C was 18.1%. Reduction in LDL-C of > 40% occurred in 19.6% of the patients. In conclusion, treatment with fluvastatin XL 80 mg once daily for 8 weeks in this PMS was shown to be safe and well tolerated, and also effective in reducing LDL-C, TC and TG, and raising HDL-C in daily clinical practice.

Safety and tolerability of moxifloxacin in the treatment of respiratory tract infections: a post-marketing surveillance conducted in Indonesia.

Moxifloxacin 400 mg tablet has been marketed in Indonesia for several indications, i.e. acute exacerbation of chronic bronchitis (AECB), community-acquired pneumonia (CAP), and acute bacterial sinusitis (ABS). To assess the safety and tolerability of moxifloxacin, a post-marketing surveillance study was conducted in the year 2001 involving 589 physicians. Clinical efficacy was also evaluated, both by physicians and patients, using a 6-symptom total score, which was scaled 0-12. A total of 1715 patients with acute sinusitis, CAP, AECB, and other infections were treated with oral moxifloxacin 400 mg once daily. There were 151 (8.8%) patients with adverse events (AEs) and 5 (0.29%) patients with serious adverse events (SAEs) that were considered related to moxifloxacin treatment. The most common adverse reactions were nausea (4.96%), dizziness (1.52%), vomiting (0.64%), headache (0.47%), and weakness (0.47%). Twenty three (1.34%) patients discontinued treatment due to adverse events. Tolerance to treatment was rated very good and good by 647 (37.7%) and 919 (53.6%) of patients, respectively. Based on physicians’ clinical assessment, 57.7% of patients were cured and 39.9% were improved at the end of treatment. Mean total symptom score, as assessed by the patients, decreased from 6.43 on day-1 to 2.76 on day-3. Totally, 95.3% of patients felt better after receiving moxifloxacin and 97.6% of patients had good impression on moxifloxacin treatment. In conclusion, treatment of respiratory tract infections, mainly AECB, CAP and ABS, with moxifloxacin 400 mg once daily in this post-marketing surveillance was shown to be safe and well tolerated. Moxifloxacin was also shown to be highly effective in the treatment of these infections with rapid improvement of symptoms.

Clinical efficacy and tolerability of mometasone furoate nasal spray in perennial allergic rhinitis patients : an open multicentre study.

Mometasone furoate (MF) aqueous nasal spray has been shown to be effective and well-tolerated in the treatment of perennial allergic rhinitis (PAR). All of the sudies, however, have been conducted in Canada, UK, and Europe. Therefore, a bridging study is warranted in view of the different climatic conditions in tropical countries. To evaluate the clinical efficacy and tolerability of MF aqueous nasal spray in the treatment of PAR in a tropical country. This study was an open, non comparative, 4-week 3-centre trial in outpatients of 12 to 60 years with moderate to severe PAR of at least 2 years duration. Patients were allergic to at least one major PAR allergen, confirmed by skin prick test. They had total nasal symptom score (TNSS) of ≥ 6 and nasal congestion score (NCS) of ≥ 2 on ≥ 3 diary time points prior to baseline visit and at both screening and baseline visits. Eligible patients received MF aqueous nasal spray at baseline visit, and administered 200 µg mometasone every morning for 4 weeks. The primary clinical efficacy parameter was the mean percentage reduction of TNSS from baseline. Of 100 eligible patients, all completed this 4-week trial. The patient-evaluated TNSS (sum of the Last 3 mornings) decreased signiftcantly from baseline with a mean reduction of 60.9 % (p < 0.0001,) at week-2 and 73.6 % (p < 0.0001) at week-4. The mean reductions in physician-rated TNSS (61.7 % at week-2 and 77.8 % at week-4) were higher than those in the previous studies (43 % and 51 % at week-2, 52 % and 54 % at week-4). Similar trends were observed for nasal congestion score (NCS), other individual symptoms, total symptoms, and clinical efficacy rates. Evening symptoms were reduced similarly as morning symptoms There was no withdrawal due to adverse event. MF aqueous nasal spray, at a dose of 200 µg once daily in the morning for the treatment of moderate to severe PAR in a tropical country, was clinically effective with 24-hour control of PAR symptoms, and was well tolerated.

Comparison of the effïcacy and safety of isepamicin plus metronidazole and amikacin plus metronidazole in intra-abdominal infections.

Intra-abdominal infections due to penetrating wound through the abdominal wall or rupture of the gastrointestinal tract are acute conditions requiring prompt surgical intervention and the use of appropriate antimicrobial agents. Isepamicin is an effective aminoglycoside against various Gram-negative pathogens causing intra-abdominal infections. The objective of the present study is to compare the efficacy and safety of isepamicin (15 mg/kgBW IV o.d.) with amikacin (7.5 mg/kgBB b.i.d.), in conjunction with metronidazole for both drugs. An open, randomized, parallel design was applied in this trial. The subject allocation ratio for isepamicin: amikacin is 2:1. Out of 50 patients enrolled in this study, 27 fuffilled the criteria for safety and efficacy population, and 46 for intent-to-treat population. In the safety and efficacy population, the clinical success rare for isepamicin and amikacin group did not differ significantly (i.e., 95% and 100%, respectively). In the intent-to-treat population, the clinical success rates for isepamicin and amikacin group were also insignifficantly different (i.e., 97% and 100%, respectively). The rates of bacteriological elimination for isepamicin and amikacin, were 95% and 100%, respectively in the efficacy and safety population, and 90% and 93%, respectively in the intent-to-treat population. Streptococci and staphylococci were the most frequent (40%) pathogens isolated from pus, and Acinetobacter anitratus (55%) was the most common one isolated from blood. In the efficacy and safety population, the mean (± SD) length of hospital stay in the isepamicin and amikacin groups was 10.7 ± 3.9 and 11.1 ± 3.8 days, respectively, while in the intent-to-treat population, the mean (± SD) length of hospital stay in the isepamicin and amikacin groups was 10.1 ± 3.4 and 10.5 ± 3 days, respectively. In the present study, both aminoglycosides were well tolerated and there was no patient withdrawal associated with side effect. It is concluded that for intra-abdominal infections, intravenous isepamicin given once daily is as effective as intravenous amikacin given twice daily in combination with metronidazole.