Lithostat (acetohydroxamic acid) Contraindications

About Lithostat^®

Acetohydroxamic acid should not be used in:

patients whose physical state and disease are amenable to definitive surgery and appropriate antimicrobial agents
patients whose urine is infected by non-urease producing organisms
patients whose urinary infections can be controlled by culture-specific oral antimicrobial agents
patients whose renal function is poor (i.e., serum creatinine more than 2.5 mg/dl and/or creatinine clearance less than 20 ml/min)
female patients who do not evidence a satisfactory method of contraception
patients who are pregnant

Acetohydroxamic acid may cause fetal harm when administered to a pregnant woman. AHA was teratogenic (retarded and/or clubbed rear leg at 750 mg/kg and above and exencephaly and encephalocele at 1,500 mg/kg) when given intraperitoneally to rats. AHA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the fetus.

Important Safety Information

Warnings

A Coombs negative hemolytic anemia has occurred in patients receiving AHA. Gastrointestinal upset characterized by nausea, vomiting, anorexia and generalized malaise have accompanied the most severe forms of hemolytic anemia. Approximately 15% of patients receiving AHA have had only laboratory findings of an anemia. However, most patients developed a mild reticulocytosis. The untoward reactions have reverted to normal following cessation of treatment. A complete blood count, including a reticulocyte count, is recommended after two weeks of treatment. If the reticulocyte count exceeds 6%, a reduced dosage should be entertained. A CBC and reticulocyte count are recommended at 3-month intervals for the duration of treatment .

Precautions

Bone marrow depression (leukopenia, anemia, and thrombocytopenia) has occurred in experimental animals receiving large doses of AHA, but has not been seen in man to date. AHA is a known inhibitor of DNA synthesis and also chelates metals - notably iron. Its bone marrow suppressant effect is probably related to its ability to inhibit DNA synthesis, but anemia could also be related to depletion of iron stores. To date, the only clinical effect noted has been hemolysis, with a decrease in the circulating red blood cells, hemoglobin and hematocrit. Abnormalities in platelet or white blood cell count have not been noted. However, clinical monitoring of the platelet and white cell count is recommended.

Abnormalities of liver function have not been reported to date. However, a chloro-benzene derivative of acetohydroxamic acid caused significant liver dysfunction in an unrelated study. Therefore, close monitoring of liver function is recommended.

Since AHA is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored, and a reduction of daily dose may be needed to avoid excessive drug accumulation.

This material is intended to provide basic information. Patients should discuss all medical advice, diagnosis, and treatment with their healthcare provider.

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