Antileishmania drugs
Pentavalent antimonials (sodium stiboglucinate and meglumine antimoniate)
These drugs have been the first line treatment for VL since 1940s. The available preparations are Pentostam (Sodium stibogluconate 100mg SB/ml) and Glucantime (meglumine antimoniate) 85mg SB/ml). They are similar in their chemical nature and also have similar toxicity profile due to the antimony content. They can be administered intramuscularly or slow intravenous infusion (5-10min). Intralesional administration is also possible in case of CL. Once administered, the drug is almost totally excreted within 6 hours via urine.
Adverse events:
Cardiotoxicity – early flattening of T waves and QT prolongation, followed by life threatening arrhythmias. Cardiotoxicity is often associated with higher doses and a maximum dose of 850mg/day was set previously. But the dose should not be limited to maximum of 850mg/day. Those patients requiring higher doses need to be followed with ECG. The dose has to be adjusted in renal failure patients. Particular attention should be given to those with prior cardiac illnesses.
Pancreatitis – The presence of severe abdominal pain and repeated vomiting herald pancreatitis. Elevation of pancreatic enzymes (amylase, lipase) is also observed. This may be self-limiting and may need transient discontinuation of the drug. However, when combined with renal failure, it has poor prognosis and the treatment should better be changed to a safer alternative.
Other adverse events include thrombophlebitis, anorexia, myalgia, arthralgia, elevation of liver transaminases.
Amphotericin B
There are conventional and liposomal forms. The conventional formulation is nephrotoxic and causes hypokalemia. The liposomal form has enhanced tissue distribution and longer tissue half-life, less toxicity and shorter duration of treatment. Liposomal amphotericin B is now the safest and most effective treatment recommended as first line in developed countries. However, its effectiveness differs with geographic locations. Infusion related reactions are common adverse effects. Acetaminophen, diphenhydramine or low doses of corticosteroids can decrease infusion related reactions. Liposomal amphotericin B needs to be kept at a temperature between 2˚C -25˚C, otherwise, the formulation can be damaged and more adverse reaction can occur.
Paromomycin
An aminoglycoside drug with variable efficacy depending on the geographic location – effective in Indian subcontinent but less so in East Africa. It is used in combination with the other drugs (antimonials) to increase its effectiveness.
It has nephrotoxicity and ototoxicity effects. Close monitoring of renal function and hearing is important.
Miltefosine
This was an anti-cancer drug that was found to have effect against leishmania. It has long half-life (150hours) and liable for resistance development. It is recommended to be used in combination with the other antileishmania drugs. It is teratogenic and effective contraception means is required for months during and after it is given to reproductive age women. Common adverse effects are nausea, vomiting, anorexia and diarrhea. These often are self-limiting and can be reduced by administration of the drug together with fatty meal.
Pentamidine
This is effective drug against leishmania but abandoned from use due to its toxicity when used in frequent dosing like daily or every other day. Can be alternative treatment for frequently relapsing, non-curing patients with other medicines. It can also be used for secondary prophylaxis in high risk relapsing patients. Adverse events include, diabetes mellitus, severe hypoglycemia, shock, myocarditis and nephrotoxicity.