The administration of leucovorin and levoleucovorin as well as other active, reduced folates are useful as an antidote to drugs which act as folic acid antagonists and in combination chemotherapy with 5-FU.The most often used calcium salts of the folates have a low solubility in water. Therefore aqueous solutions are unstable and precipitates are resulting. Precipitates in injectable products present an unacceptable risk to patients.Stable high strength pharmaceutical aqueous compositions containing calcium salts, magnesium or zinc salts of the reduced folates leucovorin, levoleucovorin, (6R,S)-tetrahydrofolic acid, (6S)-tetrahydrofolic acid, 5,10-methylene-(6R,S)-tetrahydrofolate, 5,10-methylene-(6R)-tetrahydrofolate, 5-methyl-(6R,S)-tetrahydrofolate or 5-methyl-(6S)-tetrahydrofolate and one or more of the compounds sodium gluconate, potassium gluconate, magnesium gluconate, calcium gluconate, sodium lactate, potassium lactate, magnesium lactate, calcium lactate, glycerophosphate disodium salt, glycerophosphate dipotassium salt glycerophosphate calcium salt or glycerophosphate magnesium salt are disclosed.
