McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 4  Antineoplastic agents

TABLE 14.3

DRUGS IN FOCUS Antineoplastic antibiotics (continued)

Drug name

Dosage/route

Usual indications

mitoxantrone (generic)

14 mg/m 2 per day IV every 2 days

Part of combination therapy in the treatment of adult leukaemias; treatment of bone pain in advanced prostatic cancer Special considerations: severe bone marrow suppression may occur and limits dose; alopecia, GI toxicity and congestive heart failure often occur; avoid direct skin contact with the drug—use gloves and goggles; monitor bone marrow activity and cardiac activity to adjust dose or discontinue drug as needed

Pharmacokinetics The antineoplastic antibiotics are not absorbed well from the GI tract. They are given intravenously (IV) or injected into specific sites. They are metabolised in the liver and excreted in the urine at various rates. Many of them have very long half-lives (e.g. 45 hours for idarubicin; more than 5 days for mitoxantrone). Dauno­ rubicin and doxorubicin do not cross the blood–brain barrier, but they are widely distributed in the body and are taken up by the heart, lungs, kidneys and spleen. This can lead to toxic effects in these organs. Contraindications and cautions All of these agents are contraindicated for use during pregnancy and breastfeeding because of the potential risk to the fetus and neonate . Use caution when giving antineoplastic antibiotics to an individual with a known allergy to the antibiotic or related antibiotics. Care is necessary when administering these agents to indi­ viduals with the following conditions: bone marrow suppression, which is often the index for re-dosing and dosing levels ; suppressed renal or hepatic function, which might interfere with the metabolism or excre- tion of these drugs and often indicates a need to change the dose ; known GI ulcerations or ulcerative diseases, which may be exacerbated by the effects of these drugs ; pulmonary problems with bleomycin or mitomycin, or cardiac problems with idarubicin or mitoxantrone, which are specifically toxic to these organ systems. Adverse effects Adverse effects frequently encountered with the use of these antibiotics include bone marrow suppression, with leucopenia, thrombocytopenia, anaemia and pancyto­ penia, secondary to the effects of the drugs on the rapidly multiplying cells of the bone marrow. Toxic GI effects include nausea, vomiting, anorexia, diarrhoea and mucous membrane deterioration, all of which are related to drug effects on the rapidly multiplying cells of the GI

tract. As with the alkylating agents and antimetabolites, effects of antineoplastic antibiotics may include renal or hepatic toxicity, depending on the exact mechanism of action. Alopecia may also occur. Specific antineoplastic antibiotics are toxic to the heart and lungs. Clinically important drug–drug interactions Antimetabolites that are known to cause hepatic or renal toxicity should be used with care with any other drugs known to have the same effect. Drugs that result in toxicity to the heart or lungs should be used with caution with any other drugs that produce that particu­ lar toxicity. Check for specific drug–drug interactions for each agent in a nursing drug guide. Prototype summary: Doxorubicin Indications: To produce regression in acute lymphoblastic lymphoma, acute myeloblastic leukaemia, Wilms tumour, neuroblastoma, soft tissue and bone sarcoma, breast carcinoma, ovarian carcinoma, thyroid carcinoma, Hodgkin’s and non-Hodgkin’s lymphomas, bronchogenic carcinoma; also to treat AIDS-related Kaposi’s sarcoma. Actions: Binds to DNA and inhibits DNA synthesis in susceptible cells, causing cell death. Pharmacokinetics: Route Onset Peak Duration IV Rapid 2 hours 24–36 hours T 1/2 : 12 minutes, then 3.3 hours, then 29.6 hours; metabolised in the liver and excreted in the bile, faeces and urine. Adverse effects: Cardiac toxicity, complete but reversible alopecia, nausea, vomiting, mucositis, red urine, myelosuppression, fever, chills, rash.