antimony-sodium-gluconate and Drug-Related-Side-Effects-and-Adverse-Reactions

Several attempts have been made to combine drugs for treating visceral leishmaniasis, but only recently have effective drugs become available and combinations been tested systematically.. Sequential treatments with liposomal amphotericin B followed by miltefosine or paromomycin (as short as 7 days), as well as the concomitant administration of miltefosine and paromomycin (for 10 days) are very effective in India (>95%). Sodium stibogluconate plus paromomycin for 17 days is more than 90% effective in East Africa. The shortened combination regimens are cost-effective in India. No combination has been tested so far in Brazil, Nepal and Bangladesh, although studies may be expected in the near future. No cost-effectiveness analysis has been done as yet outside India.. There is evidence of high efficacy and benefits with sequential and co-administration treatments in India. More studies are needed in other endemic areas. Introducing combinations and scaling up their use will be challenging. Experience acquired with malaria may be useful. Proper monitoring of use and effects (efficacy and safety) will be required. Currently there are no options for fixed-dose combination treatments for leishmaniasis.

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Cost-Benefit Analysis; Drug Resistance; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Leishmaniasis, Visceral; Paromomycin; Phosphorylcholine

Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.. A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data.. The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens.. The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa.. www.clinicaltrials.govNCT00255567.

Topics: Adolescent; Adult; Africa, Eastern; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Leishmaniasis, Visceral; Male; Middle Aged; Paromomycin; Treatment Outcome; Young Adult

Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan. Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive.. Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50 degrees C for 30 seconds) in one session. Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months. Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM. In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053). Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm.. Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG.. ClinicalTrials.gov NCT 00884377.

Topics: Adolescent; Adult; Animals; Antimony Sodium Gluconate; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hyperthermia, Induced; Injections, Intravenous; Leishmania major; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome; Young Adult

Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach.. We reviewed records of 67 consecutive NWCL patients, aged 17-61 years, treated as day-cases with 20 mg/kg/day SbV for up to 28 days at our UK centre. Data had been collected in a standardised format at the time of treatment using a care-record tool. Patients reported adverse-effects daily using a structured questionnaire. Blood tests and electrocardiograms were performed twice weekly to monitor for toxicity.. Parenteral SbV treatment was associated with an early, significant suppression of mean lymphocyte and platelet counts. By day four of treatment, lymphocytes reduced by 0.53×10(9)/L (CI 0.29×10(9)/L to 0.76×10(9)/L, p<0.001), and platelets by 31,000/µL (CI 16,000/µL to 46,000/µL, p<0.001). SbV was further associated with significant elevation of serum alanine transaminase concentrations, with a mean peak rise of 107 iu/L by day 13 (CI 52 iu/L to 161 iu/L, p<0.001). These disturbances were temporary and did not result in adverse clinical events. Patient-described symptoms were cumulative and at three weeks of treatment, 59.6% of patients experienced myalgia and 29.8% malaise. Treatment adherence and clinical outcomes were comparable to inpatient treatment studies. A total of 1407 individual doses of SbV resulted in only 26 nights' hospital admission, a saving of 1381 bed-days compared to inpatient treatment.. In specialist centres, NWCL patients aged below 65 years and without co-morbidities can be safely and effectively treated without hospital admission. This reduces the cost of treatment, and is much preferred by patients. Twice weekly blood and electrocardiographic monitoring may be surplus to requirement in clinically well, low-risk patients.

Topics: Adolescent; Adult; Ambulatory Care Facilities; Antimony Sodium Gluconate; Antiprotozoal Agents; Case Management; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infusions, Intravenous; Leishmania; Leishmaniasis, Cutaneous; Lymphocyte Count; Male; Medication Adherence; Middle Aged; Platelet Count; Time Factors; Travel; Treatment Outcome; United Kingdom; Young Adult

Topics: Antimony Sodium Gluconate; Antiprotozoal Agents; Drug-Related Side Effects and Adverse Reactions; Heart; Humans; Leishmaniasis, Visceral