Hematologic toxicity with leukopenia

In one study, 68 patients with rheumatic disease on AZA (2 to 3 mg/kg/d) were genotyped for TPMT and TPMT3A alleles. All patients were assessed for side effects from AZA, such as leukopenia, liver function abnormalities, and GI intolerance. Of these patients, 6 (9%) patients were heterozygous for TPMT3A, of whom 5 discontinued AZA within 4 weeks of starting the medication because of hematologic toxicity (48). In another study, 40 RA patients on AZA (0.7 to 1.4 mg/ kg/d) were genotyped for the TPMT alleles. Of the 40 patients, 6 discontinued... 

The risk of hematologic toxicity (characterized by marked facial flushing, persistent nosebleeds, hemoptysis, purpura, ecchymosis, leukopenia, and thrombocytopenia) increases with administration of high dosages or more than 10 doses. 

Hematological toxicity was analysed in 199 patients treated with a high-dose intravenous bolus aldesleukin regimen for metastatic melanoma or renal cell carcinoma (60). Anemia requiring transfusions was noted in 14% of all treatment courses and severe thrombocytopenia occurred in 2.2%, with three patients suffering from serious hemorrhages. Severe leukopenia was infrequent and not associated with infectious episodes. Early transient lymphopenia (93% reduction) was followed by rebound lymphocytosis up to 198% above baseline values. Except for severe thrombocytopenia, treatment withdrawal was... 

Hematological toxicity is the most commonly reported severe adverse effect of azathioprine, and is marked by predominant leukopenia, thrombocytopenia, and pancytopenia (SED-13, 1120). In a 27-year survey of 739 patients treated with azathioprine 2 mg/kg for inflammatory bowel disease, dosage reduction or withdrawal of the drug because of bone marrow toxicity was necessary in 37 patients (5%) (11). There was moderate or severe leukopenia in 3.8% of patients in three patients pancytopenia resulted in severe sepsis or death. 

In a study using general practitioner-based computerized data, 442 543 patients were identified who received 674 148 prescriptions for chloramphenicol eye-drops. Among these patients, there were three with severe hematological toxicity and one with mild transient leukopenia. The causal hnk between topical chloramphenicol and hematological toxicity was not further evaluated in detail (40). 

The most frequent adverse effect of vinblastine, vinde-sine, and vinorelbine is hematological toxicity (1,2,5,7,8). Leukopenia, particularly neutropenia, occurs more often than thrombocytopenia or anemia. The nadir in the leukocyte count after vinblastine occurs 4-10 days after administration, with recovery within another 7-14 days. Blood counts should generally be measured weekly and before the administration of each dose, in order to avoid severe forms of myelosuppression, neutropenic fever, or infections (20). 

Thrombocytopenia and alterations in platelet aggregation occur in the patients receiving valproic acid, and these phenomena are related to serum concentration. Other hematologic toxicities have been reported, including leukopenia with transient neutropenia, transient erythroblastopenia, and bone marrow changes. Polycystic ovary syndrome and menstrual cycle irregularities also have been associated with valproic acid. ... 

The principal toxicities of mycophenolate are gastrointestinal and hematologic. These include leukopenia, diarrhea, and vomiting. There also is an increased incidence of some infections, especially sepsis associated with cytomegalovirus. Tacrolimus in combination with mycophenolate mofetil has been associated with devastating viral infections including polyoma nephritis. 

MTX is potentially toxic. Therefore, the nurse observes closely for development of adverse reactions, such as thrombocytopenia (see Nursing Alert in Gold Compounds section) and leukopenia (see discussion of adverse reactions associated with hydroxychloroquine). Hematology, liver, and renal function studies are monitored every 1 to 3 months with MTX therapy. The primary care provider is notified of abnormal hematology, liver function, or kidney function finding. The nurse immediately brings all adverse reactions or suspected adverse reactions to the attention of the primary health care provider. 

Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these dm have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic dm are not effective in controlling seizures. The oxazolidinediones may precipitate a tonic-clonic seizure... 

Toxicities are GI (stomatitis, diarrhea, nausea, vomiting), hematologic (thrombocytopenia, leukopenia), pulmonary (fibrosis, pneumonitis), and hepatic (elevated enzymes, rare cirrhosis). Concomitant folic acid may reduce some adverse effects without loss of efficacy. Liver injury tests (aspartate aminotransferase or alanine aminotransferase) should be monitored periodically, but a liver biopsy is recommended during therapy only in patients with persistently elevated hepatic enzymes. MTX is teratogenic, and patients should use contraception and discontinue the drug if conception is planned. 

Adverse Effects. The primary problem associated with foscarnet is impaired renal function, including acute tubular necrosis. Hematologic disorders (anemia, granulocytopenia, leukopenia), gastrointestinal disturbances (cramps, nausea, vomiting), and CNS toxicity (confusion, dizziness) may also occur during foscarnet treatment. 

Bone marrow suppression is a recognized toxic effect of flucytosine anemia, leukopenia, and thrombocytopenia occur in about 5% of cases. The hematological effects are dose-related and occur after prolonged high blood concentrations of flucytosine (over 100 pg/ml). Hematotoxicity is seen more often in the presence of renal insufficiency and hence during the use of flucytosine in combination with amphotericin. If bone marrow reserve has already been depleted by underlying disease or by medications, the risk of hematotoxicity increases. 

The therapeutic concentration range for optimal pharmacological effect of carbamazepine is 4 to 12p,g/mL. Toxicity associated with excessive carbamazepine ingestion occurs at plasma concentrations in excess of 15p.g/mL and is characterized by symptoms of blurred vision, paresthesia, nystagmus, ataxia, drowsiness, and diplopia. Side effects unrelated to plasma concentration include development of an urticarial rash, which usually disappears on discontinuation of the drug, and hematological depression (leukopenia, thrombocytopenia, and aplastic anemia). 

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