Antimony and antimonials

Salts of antimony

Uses

Antimony salts have in the past found many uses in medicine, and antimony compounds, especially pentavalent ones, are still used to treat Schistosoma japonicum infestation and leishmaniasis [ ]. The standard treatment of most South American cutaneous leishmaniasis is systemic, because of the propensity of the parasites to spread to mucous membranes. The drugs in common use remain parenteral, and are fairly toxic. Sodium stibogluconate, in a dose of 20 mg/kg for 30 days, remains the gold standard, with liposomal amphotericin a possible alternative. Both drugs are also the preferred choice for all strains of visceral leishmaniasis. Stibogluconate achieves a cure in certain cases [ , ] and is reasonably safe, although transient pancreatitis, musculoskeletal pains, and loss of appetite have been reported. Primary unresponsiveness (cure not obtained by the first course of treatment) is being increasingly reported [ ] and is a particular problem in the Bihar region of North-East India, where a report documented primary unresponsiveness in 33% of cases [ ]. The new treatment options for visceral leishmaniasis have been reviewed [ ].

Antimony is also used as an emetic. Attention has also been paid to the anticancer potential of antimony compounds [ , ]. As with many other metals, occupational and environmental exposure is possible and can act additively with medical exposure.

Pharmacokinetics

Antimony is excreted in the urine. Peak concentrations are seen at about 1–2 hours after an intramuscular injection of meglumine antimonate. Serum concentrations fall to about 10% of peak concentrations after about 8 hours. There is some accumulation of antimony during continued treatment. On a weight for weight basis children require a higher dose and tolerate antimony better. Toxicity is more likely in patients with impaired renal function, as would be expected for a drug that is mainly excreted in the urine.

General adverse effects and adverse reactions

Common adverse reactions to antimony treatment include anorexia, nausea, vomiting, muscle ache, headache, lethargy, and bone and joint pain.

Common adverse reactions to meglumine antimonate are anorexia, nausea, vomiting, malaise, myalgia, headache, and lethargy. Muscle, bone, and joint pains have been described [ , ]. Cardiac toxicity and electrocardiographic changes are dose-related. The general condition of the patient with visceral leishmaniasis probably plays a crucial role in these and other adverse effects. Malnutrition is common, the immune status often severely impaired, and patients are susceptible to intercurrent infections [ ].

In 96 patients with visceral, mucosal, or viscerotropic leishmaniasis, who were given sodium stibogluconate 20 mg/kg/day for 20–28 days, adverse effects were common and necessitated withdrawal of treatment in 28% of cases. They included arthralgias and myalgias (58%), pancreatitis (97%), increased transaminases (67%), headache (22%), bone marrow suppression (44%), and rash (9%) [ ]. Arthralgias are more likely to represent reactions to the tissue of the dead or dying parasite than true allergies to the drug.

In 53 patients with dermal leishmaniasis after kala-azar, who were given sodium stibogluconate 20 mg/kg/day intramuscularly, adverse effects were changes in electrocardiographic ST segments and T waves (7%), arthralgias (11%), allergic rashes (7%), swelling at the site of injection (5%), neuralgia (4%), and a metallic taste (6%) [ ].

Observational studies

The characteristics of 111 consecutive patients with visceral leishmaniasis in Sicily have been described [ ]. They were given intramuscular meglumine antimoniate (560 mg/m ² of pentavalent antimony), generally for 21 days. There were adverse effects in 16 patients, including rash (n = 3) and dry cough (n = 13). All the adverse effects bar one (a severe urticarial rash) were transient and self-limiting and did not require drug withdrawal.

The safety and efficacy of generic sodium stibogluconate (from Albert David Ltd) has been studied in patients with cutaneous leishmaniasis and mucous leishmaniasis in Bolivia, who were treated with 20 mg/kg/day for 20 and 30 days respectively. A questionnaire recording adverse effects was completed by a physician in each treatment center. Efficacy of treatment was assessed at the end of treatment and at follow-up 1, 3, 6, and 12 months later. Overall, 146 patients, previously treated with intramuscular meglumine antimoniate (Glucantime), completed intravenous treatment with generic sodium stibogluconate in 2003–4 (20 mg/kg/day, for 20 days or 30 days for cutaneous leismaniasis and mucous leishmaniasis respectively). There were no fatalities or severe adverse effects, but there were mild to moderate adverse effects in 41 patients (28%). They included arthralgias and/or myalgias (8%), headache (7%), phlebitis (4%), pain at the injection site (3%), malaise (3%), insomnia (3%), bradycardia (2%), fever (2%), vertigo (1%), vomiting (1%), weight loss (1%), pruritus (1%), and anorexia (1%). Ten (6.8%) of the patients given generic sodium stibogluconate were considered to have had moderate adverse effects, but there were no fatalities or other severe adverse effects. The incidence of adverse effects was significantly higher among the patients with mucous leishmaniasis than those with cutaneous leishmaniasis. Of the 86 patients with cutaneous leishmaniasis who completed 6 months of follow-up, 81 were considered to have been clinically cured; a comparable group of 69 patients with cutaneous leishmaniasis who had been treated with Glucantime in 2001–2 had a similar frequency of clinical cure (90%).

The authors concluded that sodium stibogluconate, being several times cheaper than Glucantime, could contribute to improving access to treatment by patients with cutaneous or mucous leishmaniasis, not only in Bolivia but also in other countries of Latin America.