Sodium Dichloroacetate

Sodium Dichloroacetate Chemical formula

Chemical information

CPC-211; DCA; Dicloroacetato de sodio.
Chemical formula: C2HCl2NaO2 = 150.9.


Dichloroacetic acid activates pyruvate dehydrogenase, a mitochondrial enzyme that catalyses metabolism of pyruvate and lactate, and it inhibits glycolysis. It also stimulates myocardial contractility. Sodium dichloroacetate has been used for the treatment of congenital lactic acidosis, lactic acidosis in patients with severe malaria, homozygous familial hypercholesterolaemia, and for severe brain injury. It is also under investigation for stroke.

Adverse effects.

Adverse effects reported with sodium dichloroacetate have mainly involved the central and peripheral nervous systems.1 Anxiolytic or sedative effects are common. Reversible polyneuropathy has been reported after chronic use, as has asymptomatic elevation of serum transaminases. Reduced urate clearance and elevated serum urate levels have been reported in patients with type 2 diabetes mellitus. See also under Use in Metabolic Acidosis, below for reference to early termination of a study due to development of peripheral neuropathy.
1. Stacpoole PW, et al. Pharmacokinetics, metabolism, and toxicology of dichloroacetate. Drug Metab Rev 1998; 30: 499–539.


1. Henderson GN, et al. Pharmacokinetics of dichloroacetate in adult patients with lactic acidosis. J Clin Pharmacol 1997; 37: 416–25
2. Shangraw RE, Fisher DM. Pharmacokinetics and pharmacodynamics of dichloroacetate in patients with cirrhosis. Clin Pharmacol Ther 1999 66: 380–90.

Use in metabolic acidosis.

In a study1 in 29 patients with lactic acidosis, sodium dichloroacetate 50 mg/kg given by intravenous infusion over 30 minutes, followed by a second dose 2 hours after beginning the first infusion, produced a metabolic response in 23 patients with a short-term increase in survival. However, a subsequent study2 found that, while dichloroacetate infusion did reduce blood-lactate concentrations, it did not alter haemodynamics or survival in patients with severe lactic acidosis. A review3 of these and other controlled studies in the treatment of acquired and congenital lactic acidosis concluded that the maximum lactate-lowering effect is dose-dependent but independent of time after dosing. Whether lowering lactate levels contributes to reducing morbidity and mortality in hyperlactataemia remains controversial, although data from recent studies suggest that treatment in mild cases may reduce the risk of death. A review4 of the treatment of children with dichloroacetate for congenital lactic acidosis hypothesised that it might improve quality of life by reducing the frequency of acid–base decompensations, improving neurological function, and stimulating linear growth. A randomised controlled study5 of dichloroacetate for the treatment of congenital lactic acidosis in 43 patients ranging in age from 3 months to 18 years found that dichloroacetate for 6 months was well tolerated and reduced blood-lactate response to a carbohydrate challenge but had no effect on basal-lactate concentrations nor did it improve neurologic or other measures of clinical outcome. In another randomised controlled study6 of the effects of dichloroacetate in the treatment of the multisystem syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 13 of 15 patients given the study medication developed peripheral neuropathy, displaying either clinical signs and symptoms or electrophysiological evidence. The study was therefore stopped early, and on this basis, the authors concluded that dichloroacetate could not be recommended for the treatment of MELAS. In a randomised, double-blind, placebo-controlled study7 in 124 West African children with severe Plasmodium falciparum malaria, a single intravenous infusion of sodium dichloroacetate in a dose of 50 mg/kg given at the same time as quinine increased the rate and magnitude of fall in blood-lactate levels without compromising the plasma kinetics of quinine. In the UK, the BNFC includes the following doses for neonates and children with pyruvate dehydrogenase defects: 12.5 mg/kg 4 times daily by mouth, adjusted according to response up to 200 mg/kg daily. Sodium dichloroacetate has also been studied8 in patients with traumatic brain injury for its lactate-lowering effect in cerebrospinal fluid.
1. Stacpoole PW, et al. Dichloroacetate in the treatment of lactic acidosis. Ann Intern Med 1988; 108: 58–63
2. Stacpoole PW, et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. N Engl J Med 1992; 327: 1564–9
3. Stacpoole PW, et al. Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol 2003; 43: 683–91
4. Stacpoole PW, et al. Treatment of congenital lactic acidosis with dichloroacetate. Arch Dis Child 1997; 77: 535–41
5. Stacpoole PW, et al. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics 2006; 117: 1519–31
6. Kaufmann P, et al. Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology 2006; 66: 324–30
7. Agbenyega T, et al. Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children. J Clin Pharmacol 2003; 43: 386–96
8. Williams PJ, Dichloroacetate: population pharmacokinetics with a pharmacodynamic sequential link model. J Clin Pharmacol 2001; 41: 259–67.
Published May 08, 2019.