Potassium hexahydroxoantimonate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: human data

Adequacy of study:

weight of evidence

Study period:

December 1986 to September 1987

Reliability:

other: high

Rationale for reliability incl. deficiencies:

other: The publication has a high reliability. Comment: Adequate number of patients, considerably extended duration over conventional treatment regime.

Data source

Reference

Reference Type:

publication

Title:

Efficacy of prolonged therapy with stibogluconate in post kala-azar dermal leishmaniasis

Author:

Thakur, C.P. & Kumar, K.

Year:

1990

Bibliographic source:

Indian J. Med. Res. [A], 91: 144 - 148.

Materials and methods

Study type:

clinical case study

Endpoint addressed:

not applicable

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Fifty three (30 male and 23 female), previously untreated, patients with post kala-azar dermal lesihmaniasis (PKDL) were treated with sodium stibogluconate, at the dose of 20 mg/kg/bw/d/im/ (with a maximum of 8.5 ml) for 120 days (or more, if necessary) All patients were followed up for 12 months. The patients were assessed after 40 days and thereafter at an interval of 20 days. Clinical observation, urine analysis, heamtological and biochemical examinations, and electrocardiography were done.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

sodium stibogluconate (SSG)

IUPAC Name:

sodium stibogluconate (SSG)

Details on test material:

- Name of test material (as cited in study report): sodium stibogluconate
No further information on the test material was stated.

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 53 patients
- Sex: 30 males / 23 females
- Age: Six (11%) patients were in the age groups of 0 - 10 yr, 24 (45 %) patients in the 11 - 20 yr, 12 (23%) in 21 - 30 yr, 8 (5%) in 31 - 40 yr, no patient in 41 - 50 yr and 3 patients in the age group of 51 - 60 yr. The mean age was 23.8 yr (SD 11.1).
- Race: The race was not stated.
Only those patients of post kala-azar dermal leishmaniasis (PKDL), who did not receive any drug treatment for PKDL during last six months, were included in this study. Patients with morphological features of PKDL were admitted to the trial.In all patients, attempts were made to isolate the parasites. Those patients who were not sure of returning for follow up for one year were excluded.
The lesions were distributed all over the body. Thus they were found on the face in52 (98%), on the upper limb 38 (72 %), on lower limbs 18 (40%), on the genitelias in 3 (&%), on the tongue in 2 (4%) and on the trunk in 44 (83%) patients.
The morphology of the lesions showed hypopigmented macules in 24 (45%), erythematous macules in 4 (7%), papules in 16 and nodules in 10 patients. In most cases, the lesions were mixed in type. The nodular and papular lesions were erythematous.

Ethical approval:

not specified

Route of exposure:

other: intramuscular

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

See "Medical treatment" below

Examinations:

The clinical state of each patient was thoroughly assessed before starting the treatment. Along with the previous history of kala-azar, duration of treatment and actual drug used, interval between the attacks of kala-azar and PKDL, progress of the disease, and the duration of illness were noted. A careful study of morphology of the lesions and their distribution was made. The patient was subjected to a thorough clinical examination.
- Urine analysis was conducted
- Haematology: Total and differential WBC counts and heamoglobin protein concentration were estimated.
- Biochemical examination: Serum protein concentration,serum alanine transaminase and aspartate transaminase activities were estimated.
- Other: Chest X-ray examination and electrocardiography were done.
Skin smears were taken for demonstration of parasites and stained with Ziemsa and cultured in NNN media. Skin biopsy was also done in selected patients. Skin and nasal smear examinations for lepra bacili and malassezia furfur were done to exclude leprosy and pitriasis versicolor.
After medical treatment started:
All the patients were examined for disappearance of the lesions. Patients were instructed to report toxic effects such as anorexia, rashes, muscle pain, hypersensitivity reaction, palpitation and yellowness of the eye and arthralgia.
Leucocyte count, electrocardiogram, serum glutamic oxaloacetic transaminase, and urine examination were repeated every 20th day.
Complete cure was defined as disappearance of lesions and no relapse during 12 month of follow up. The patients were followed up every month for 12 months.
No further information on examinations was stated.

Medical treatment:

Patients were treated with sodium stibogluconate given at the dosage of 20 mg/kg/bw/d/im with a maximum of 8.5 ml for 120 days or more, if necessary. The drug was given in full dosage from the first day of treatment.

No further information on the medical treatment was stated.

Results and discussion

Clinical signs:

Six patients developed arthralgia which responded to indomethacin and withdrawal of sodium antimony gluconate for 10 days. Pain and swelling occurred due to the large quanity of the drug used at the site of injection in 8 patients. Neuritic features developed in two patients, improved after discontinuing the drug for 10 days. Three patients complained of change in taste, which did not require any treatment. All the patients thus tolerated well the longer course of treatment.

Results of examinations:

- Urine analysis: Not stated
- Haematology: Not stated
- Other: Four patients showed ECG changes (ST and T changes) and the drug was discontinued for 20 days in these cases. The ECG changes reverted to normal and the drug was started again.

Effectivity of medical treatment:

In this case the test substance is the medical treatment. For effectiveness see "Outcome of incidence" below.

Outcome of incidence:

The response of treatment started within 20 days in 72 per cent patients and within 40 days in all cases. Within 60 days, the nodules and papules started disappearing, while the macules started fading. Nodules disappeared in 8 patients, papules in 12, while macules also started disappearing after 100 injections. Within 120 days, the nodules and papules disappeared in all patients. macules however, persisted in 6 patients. While 47 patients (88%) were cured, two required further treatment for 60 days (i.e., a total of 180 days), two others required treatment for 80 days more on the same dosage (i.e., a total of 200 days). Patients with more extensive lesions needed longer duration of treatment.

Applicant's summary and conclusion

Conclusions:

Curing rate:
88 % (47 patients) within 120 days; 4 patients required further treatment (2 patients for a total of 180 days and 2 other for a total of 200 days). 2 patients needed treatment for >200 days.
Adverse effects:
Treatment has to be interrupted for 20 days in four patients due to ECG changes. Main side effects of the treatment were changes in ST and T in electrocardiogram (7%), arthralgia (11 %), allergic rash (7%), swelling at the injection side (5 %), neuralgia (4%) and metallic taste (6%)

tentative LOAEL:
not assignable