antimony-sodium-gluconate and Arrhythmias--Cardiac

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Arrhythmias, Cardiac; Electrocardiography; Female; Humans; Leishmaniasis, Visceral; Male

Kala-azar or visceral leishmaniasis is a disseminated protozoal infection caused by parasites of the genus Leishmania (Leishmania donovani in India). Conventional therapy for visceral leishmaniasis continues to be pentavalent antimony (sodium antimony gluconate [SAG]). Amphotericin B is widely used for SAG-unresponsive cases and sometimes even as a first-line drug, especially in endemic areas. With the conventional regimen of SAG, cardiac toxicity has been reported in 8% to 17% of cases with 5% to 7% of them having fatal toxicity. Cardiac toxicity is uncommon with amphotericin B with only few isolated reports. We report some patients with kala-azar in whom coadministration of SAG and amphotericin B led to arrhythmia and sudden death.

Topics: Amphotericin B; Antimony Sodium Gluconate; Antiprotozoal Agents; Arrhythmias, Cardiac; Child; Child, Preschool; Drug Therapy, Combination; Fatal Outcome; Humans; India; Leishmania donovani; Leishmaniasis, Visceral; Male

Use of parenteral pentavalent antimonials to treat leishmaniasis is associated with a range of cardiological, biochemical and haematological adverse effects. The most serious of these is the development of ventricular tachyarrhythmias associated with prolongation of the electrocardiographic rate-corrected QT interval (QTc). Whereas some studies have reported that serious cardiological and biochemical adverse effects are common and often require treatment interruption or discontinuation, others have reported the drugs to be well tolerated. We conducted a detailed retrospective analysis of adverse events among British returned travellers (n=65) with New World cutaneous or mucosal leishmaniasis who received i.v. sodium stibogluconate (SbV) for >or=21 days. The mean+/-SEM QTc progressively increased from 389+/-3.1 msec to 404+/-2.9 msec during 3 weeks of treatment and the QTc reached the threshold for potential cardiac toxicity among 6 (10%) patients during the third week of treatment. Marked QTc prolongation and ventricular tachyarrhythmias occurred in one elderly patient with hypokalaemia and pre-existing cardiovascular morbidity. Although increased serum concentrations of amylase and hepatic transaminases were observed among 67% and 85% of patients respectively, none developed clinical pancreatitis or hepatitis and treatment modification was not required. SbV can be used safely in this population with adequate monitoring and the need for treatment interruption is uncommon. Identification of factors before and during treatment that may increase the risk of QTc prolongation and arrhythmias is important.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimony Sodium Gluconate; Antiprotozoal Agents; Arrhythmias, Cardiac; Electrocardiography; Female; Humans; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Retrospective Studies; Travel

Eighty parasitologically confirmed cases of visceral leishmaniasis (kala-azar) in Bihar, India, were treated daily with 20 mg sodium stibogluconate/kg for 30 days, to assess the current efficacy and toxicity of this 30-day regimen. Clinical and parasitological cure was obtained in 48 (60%) of the patients. However, 26 (33%) patients did not respond to the first course of treatment (primary unresponsiveness), two relapsed after initial clinical and parasitological cure, and two were withdrawn from the study (one on day 6 of treatment because of cardiotoxicity in the form of supraventricular tachycardia and the other on day 24 because of severe loss of appetite). All 30 patients who were not entirely cured with sodium stibogluconate were successfully treated with amphotericin B. Electrocardiographic changes occurred in many of the patients as the result of treatment with sodium stibogluconate. Diminution in the height of the T wave was seen in 32 (40%), inversion of the T wave (Minnesota code 5-1, 5-2) in seven (9%), elevation of the ST segment (Minnesota code 4-1) in three (4%), prolonged QT interval (compared with baseline findings) in six (8%), and diminution in the height of the P, R and T waves in two (3%). Cardiac arrhythmia occurred in five patients (6%), supraventricular arrhythmia (coarse atrial fibrillation) occurred in one patient and ventricular tachycardia, ventricular fibrillation, torsade de pointes and multifocal ventricular ectopics occurred in the four patients (5%) who died of cardiotoxicity. Minor side-effects, such as pain at the site of injection (two cases), mild diminution in appetite (12 cases), metallic taste in mouth (six cases), and joint pain (two cases), were also observed. It was concluded that the efficacy of sodium stibogluconate in the study area has declined over the years and that its toxicity has increased. A more efficacious, safer and cheaper, alternative drug is required as the first line of treatment of kala-azar.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Arrhythmias, Cardiac; Child; Drug Resistance; Electrocardiography; Female; Heart Arrest; Humans; India; Leishmaniasis, Visceral; Male; Middle Aged; Treatment Outcome

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Arrhythmias, Cardiac; Child; Electrocardiography; Gluconates; Humans; Leishmaniasis, Visceral

Serial electrocardiograms (ECGs) were obtained during 65 courses of sodium stibogluconate treatment in 59 Kenyan patients with leishmaniasis (56 visceral and 3 cutaneous). ECG abnormalities developed during 54% of the treatment courses. The frequency with which abnormalities occurred was related to the total daily dose of antimony (Sb), increasing from 2/9 patients treated with 10 mg Sb/kg/d to 25/48 treated with 20-30 mg Sb/kg/d and 8/8 treated with 40-60 mg Sb/kg/d. The frequency with which ECG abnormalities developed was also related to the duration of treatment, increasing from 11/65 patients after 7 days to 18/44 after 15 days, 26/39 after 30 days and 11/12 after 60 days. ECG abnormalities were similar to those previously described during treatment with trivalent antimonial drugs, the most common being flattening and/or inversion of T waves. Prolongation of the corrected QT interval occurred in 13 patients, all of whom were treated for more than 30 days or with more than 20 mg Sb/kg/d. One patient died suddenly during the fourth week of treatment with 60 mg Sb/kg/d, and 2 patients died of measles after 9 or 10 days of treatment with 30 mg Sb/kg/d. QT prolongation and a concave ST segment developed in all 3 patients who died. We conclude that minor ECG abnormalities are common when sodium stibogluconate is used at doses above 20 mg Sb/kg/d for more than 15 days, and that life-threatening arrhythmias may occur if very high doses are used.

Topics: Adolescent; Adult; Antimony Sodium Gluconate; Arrhythmias, Cardiac; Child; Dose-Response Relationship, Drug; Electrocardiography; Gluconates; Heart Rate; Humans; Leishmaniasis; Leishmaniasis, Visceral; Male; Middle Aged