Lithostat Side Effects Information for Patients

What are the side effects with Lithostat^® ?

The complete spectrum of side effects induced by Lithostat^® (acetohydroxamic acid) is unknown. However, some side effects which have been reported to date have been headaches, abdominal discomfort, nausea, loss of hair, shakiness, and anemia. Life-threatening problems (blood clot in the legs) occurred in several patients with advanced disease in early investigation. In more extensive later investigations, this problem has not occurred. No patient has died as a consequence of taking Lithostat^®. The most serious side effects seem to occur in patients with poor kidney function and/or in patients with a previous history of these conditions.

Problems related to Lithostat^® have disappeared following cessation of the drug and initiation of appropriate medical treatment. Most patients have resumed treatment without ill effect.

A flushing skin reaction (i.e., redness, warmth, and tingling) has occurred in several patients who consumed alcohol during treatment with Lithostat^®. The reaction persisted approximately 30 minutes and disappeared without treatment. The cause and significance of this reaction are unknown. Consequently, patients are encouraged to abstain from consumption of alcoholic beverages while being treated with Lithostat^®.

In animal studies doses of Lithostat^® about 20 times the maximum human dose have caused fetal abnormalities (birth defects) indicating a potential for such an adverse effect in an exposed human fetus. Therefore, Lithostat^® should not be given to pregnant women or to any sexually active woman of child-baring age, not using a highly effective method of contraception (oral contraceptive or IUD).

An acceptable long-term study of the cancer causing potential of Lithostat^® has not been conducted, but a known metabolite of Lithostat^®, acetamide, is carcinogenic (cancer-causing) to the liver in rats at doses about 80 times the maximum human dose of Lithostat^®. Lithostat^® thus must be considered a potential human carcinogen. Lithostat^® kills tissue cells grown in tissue culture and alters genetic material in cells grown in culture.

Lithostat^® may induce other adverse reactions which have not yet been recognized.

Unusual symptoms should be reported to your physician. Mild symptoms usually do not warrant discontinuation of treatment. Severe symptoms may necessitate temporary cessation of treatment and/or alteration of dosage.

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.

Please see full Prescribing Information