POISINDEX MANAGEMENTS





                                       ZIDOVUDINE

�   0.0 OVERVIEW

        � 0.1 LIFE SUPPORT

              � A. This overview assumes that basic life support measures have been instituted.

        � 0.2 CLINICAL EFFECTS

              � 0.2.1 SUMMARY OF EXPOSURE

                     � A. Several cases of acute overdose with zidovudine have been reported in the

                         literature with minimal effects.

                     � B. Lethargy, fatigue, and mild bone marrow suppression occurred after ingestion

                         of 20 grams. An isolated seizure occurred after 36 grams. Based on the adverse

                         drug reaction profile, bone marrow suppression might be expected to occur after

                         overdosage.

                     � C. Chronic effects of zidovudine therapy may include a syndrome of fatal lactic

                         acidosis and hepatic failure.

              � 0.2.7 NEUROLOGIC

                     � A. Seizures have been rarely reported following therapeutic use, and have

                         occurred after overdose.

                     � B. Headache was experienced in a patient who took an overdose of zidovudine,

                         in combination with ketoconazole. The amount of zidovudine and ketoconazole

                         ingested were not specified.

                     � C. Fatigue was experienced in a patient who took an overdose of zidovudine, in

                         combination with ketoconazole. The amount of zidovudine and ketoconazole

                         ingested were not specified.

              � 0.2.8 GASTROINTESTINAL

                     � A. Spontaneous nausea and vomiting may occur following overdose.

              � 0.2.9 HEPATIC

                     � A. Hepatotoxicity has been reported during therapeutic use; it tends to appear

                         after several weeks of therapy. A syndrome of fatal lactic acidosis and hepatic

                         failure has been reported after several months of therapy.

              � 0.2.11 ACID-BASE

                     � A. Severe lactic acidosis, refractory to bicarbonate infusions, has been reported

                         as an adverse effect of zidovudine, after several months of therapy.

              � 0.2.13 HEMATOLOGIC

                     � A. The most common dose-related adverse effect is bone marrow suppression,

                         resulting in granulocytopenia and macrocytic anemia.

                     � B. Acute overdoses up to 50 grams have resulted in transient, non-severe

                         hematologic changes.

              � 0.2.14 DERMATOLOGIC

                     � A. Transverse nail pigmentation has been reported.

              � 0.2.15 MUSCULOSKELETAL

                     � A. Myalgia has been reported following therapeutic use in about 8% of patients;

                         however, myopathy has been reported in AIDS patients not receiving

                         zidovudine, making the connection to zidovudine questionable.

              � 0.2.18 PSYCHIATRIC

                     � A. Manic syndrome has been reported during therapeutic use.

              � 0.2.21 CARCINOGENICITY

                     � A. Extremely large doses have been associated with vaginal neoplasms in mice

                         and rats; the significance in humans is not known.

        � 0.3 LABORATORY/MONITORING

                      � A. Complete blood counts (CBC's) should be monitored intensively in patients who

                        overdose on zidovudine. Arterial blood gases and hepatic function should be monitored

                        in symptomatic patients.

                     � B. Plasma zidovudine levels do not correlate with clinical efficacy or toxicity.

             �   0.4 TREATMENT OVERVIEW

                     � 0.4.2 ORAL/PARENTERAL EXPOSURE

                             � A. In the presence of bone marrow suppression, transfusions and protective

                                 measures for granulocytopenia may be needed.

                                      � 1. Several experimental agents have been suggested as possibilities for

                                          ameliorating hematopoietic toxicity (thymidine, vitamin B12), but none

                                          have been evaluated clinically.

                             � B. Correct severe acidosis (arterial pH less than 7.1) with IV sodium bicarbonate

                                 (1 to 2 milliequivalents/kilogram).

                             � C. ACTIVATED CHARCOAL: Administer charcoal as slurry (240 mL

                                 water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in

                                 children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

             �   0.5 RANGE OF TOXICITY

                     � A. The adult therapeutic dose is 200 to 250 mg every 4 hours. This is equivalent to 2.9

                        mg/kg every 4 hours for a 70 kg man.

                     � B. Ingestion of 10 to 20 g has resulted in mild toxicity; without bone marrow

                        suppression.

                     � C. Acute overdoses of up to 50 grams have been survived by both adults and pediatrics.



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