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ZIDOVUDINE
鈥? 0.0 OVERVIEW
鈥? 0.1 LIFE SUPPORT
鈥? A. This overview assumes that basic life support measures have been instituted.
鈥? 0.2 CLINICAL EFFECTS
鈥? 0.2.1 SUMMARY OF EXPOSURE
鈥? A. Several cases of acute overdose with zidovudine have been reported in the
literature with minimal effects.
鈥? 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.
鈥? C. Chronic effects of zidovudine therapy may include a syndrome of fatal lactic
acidosis and hepatic failure.
鈥? 0.2.7 NEUROLOGIC
鈥? A. Seizures have been rarely reported following therapeutic use, and have
occurred after overdose.
鈥? 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.
鈥? 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.
鈥? 0.2.8 GASTROINTESTINAL
鈥? A. Spontaneous nausea and vomiting may occur following overdose.
鈥? 0.2.9 HEPATIC
鈥? 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.
鈥? 0.2.11 ACID-BASE
鈥? A. Severe lactic acidosis, refractory to bicarbonate infusions, has been reported
as an adverse effect of zidovudine, after several months of therapy.
鈥? 0.2.13 HEMATOLOGIC
鈥? A. The most common dose-related adverse effect is bone marrow suppression,
resulting in granulocytopenia and macrocytic anemia.
鈥? B. Acute overdoses up to 50 grams have resulted in transient, non-severe
hematologic changes.
鈥? 0.2.14 DERMATOLOGIC
鈥? A. Transverse nail pigmentation has been reported.
鈥? 0.2.15 MUSCULOSKELETAL
鈥? 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.
鈥? 0.2.18 PSYCHIATRIC
鈥? A. Manic syndrome has been reported during therapeutic use.
鈥? 0.2.21 CARCINOGENICITY
鈥? A. Extremely large doses have been associated with vaginal neoplasms in mice
and rats; the significance in humans is not known.
鈥? 0.3 LABORATORY/MONITORING
鈥? 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.
鈥? B. Plasma zidovudine levels do not correlate with clinical efficacy or toxicity.
鈥? 0.4 TREATMENT OVERVIEW
鈥? 0.4.2 ORAL/PARENTERAL EXPOSURE
鈥? A. In the presence of bone marrow suppression, transfusions and protective
measures for granulocytopenia may be needed.
鈥? 1. Several experimental agents have been suggested as possibilities for
ameliorating hematopoietic toxicity (thymidine, vitamin B12), but none
have been evaluated clinically.
鈥? B. Correct severe acidosis (arterial pH less than 7.1) with IV sodium bicarbonate
(1 to 2 milliequivalents/kilogram).
鈥? 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.
鈥? 0.5 RANGE OF TOXICITY
鈥? 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.
鈥? B. Ingestion of 10 to 20 g has resulted in mild toxicity; without bone marrow
suppression.
鈥? C. Acute overdoses of up to 50 grams have been survived by both adults and pediatrics.

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