Antimetabolites
Antimetabolites
Antimetabolites are antineoplastic drugs that inhibit DNA polymerase. They are cell-cyclephase–specific to S phase (stage of DNA synthesis), causing cell death for cells in the S phase; they also block progression of cells from G1to S in the cell cycle.
Indications
Induction and maintenance of remission in acute myelocytic leukemia (higher response rate in children than in adults), chronic lymphocytic leukemia Treatment of acute lymphocytic leukemia, chronic myelocytic leukemia and erythroleukemia, meningeal leukemia, psoriasis and rheumatoid arthritis (methotrexate) Palliative treatment of GI adenocarcinoma, carcinomas of the colon, rectum, breast, stomach, pancreas Part of combination therapy for treatment of non-Hodgkin’s lymphoma in children Contraindications and cautions
Contraindicated with allergy to the drug, pregnancy, lactation, premature infants. Use cautiously with hematopoietic depression secondary to radiation or chemotherapy; impaired liver function. Adverse effects
CNS: Neuritis, neural toxicity Dermatologic: Fever, rash, urticaria, freckling, skin ulceration, pruritus, conjunctivitis, alopecia GI: Anorexia, nausea, vomiting, diarrhea, oral and anal inflammation or ulceration; esophageal ulcerations, esophagitis, abdominal pain, hepatic impairment(jaundice), acute pancreatitis GU: Renal impairment, urine retention Hematologic: Bone marrow depression, hyperuricemia Local: Thrombophlebitis, cellulitis at injection site Other: Fever, rash Interactions
Drug-drug Decreased therapeutic action of digoxin with cytarabine Enhanced toxicity of 5-FU with leucovorin Potentially fatal reactions if methotrexate is taken with various NSAIDs Nursing considerations
Assessment
History: Allergy to drug, hematopoietic depression, impaired hepatic function, lactation Physical: Weight; T; skin lesions, color; hair; orientation, reflexes; R, adventitious sounds; mucous membranes, liver evaluation, abdominal examination; CBC, differential; LFTs; renal function tests; urinalysis Interventions
Black box
warning Arrange for tests to evaluate hematopoietic status prior to and during therapy; serious to fatal bone marrow suppression can occur. Arrange for discontinuation of drug therapy if platelet count is lower than 50,000/mm3 or polymorphonuclear granulocyte count is lower than 1,000/mm3; consult physician for dosage adjustment. Monitor injection site for signs of thrombophlebitis, inflammation. Provide mouth care for mouth sores. Provide frequent small meals and dietary consultation to maintain nutrition when GI effects are severe. Establish safety measures if dizziness, CNS effects occur. Antimetabolites 28 ? Antimetabolites Adverse effects
in italics are most common; those in bold are life-threatening. U Do not crush. Arrange for patient to obtain a wig or some other suitable head covering if alopecia occurs; ensure that head is covered in extremes of temperature. Protect patient from exposure to infections. Provide skin care. Arrange for comfort measures if anal inflammation, headache, or other pain associated with cytarabine syndrome occurs. Arrange for treatment of fever if it occurs. Teaching points
Keep the prepared calendar of treatment days available for your reference. Use birth control; these drugs may cause birth defects or miscarriages. Arrange to have frequent, regular medical follow-up, including frequent blood tests. You may experience these side effects: Nausea, vomiting, loss of appetite (medication may be ordered; frequent small meals may help; it is important to maintain nutrition); malaise, weakness, lethargy (these are all effects of the drug; consult your health care provider and avoid driving or operating dangerous machinery); mouth sores (frequent mouth care will be needed); diarrhea; loss of hair (you may wish to obtain a wig or other suitable head covering; keep the head covered in extremes of temperature); anal inflammation (consult with your health care provider; comfort measures can be ordered). Report black, tarry stools; fever, chills; sore throat; unusual bleeding or bruising; shortness of breath; chest pain; difficulty swallowing. Representative drugs
capecitabine cladribine clofarabine cytarabine floxuridine fludarabine 5-FU (fluorouracil) gemcitabine mercaptopurine methotrexate pemetrexed pentostatin rasburicase thioguanine
