McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

for possible clotting of the access line related to direct cellular effects of the drug. In 2005, post-marketing studies showed that pure red cell aplasia associated with erythropoietin-neutralising antibodies could occur with all of these products. In 2008, after analyses of several post-marketing studies, these drugs were required to add black-box warnings to their prescribing information. Clinically important drug–drug interactions These drugs should never be mixed in solution with any other drugs because of a risk of interactions in the solution. Prototype summary: Epoetin alfa Indications: Treatment of anaemia associated with chronic renal failure, related to treatment of HIV infection or to chemotherapy in people with cancer; to reduce the need for allogenic blood transfusion in people undergoing surgical procedures. Actions: Natural glycoprotein that stimulates RBC production in the bone marrow. Pharmacokinetics: Route Onset Peak Duration Subcutaneous 7–14 days 5–24 hours 24 hours T 1/2 : 4 to 13 hours; metabolised in serum and excreted in urine. Adverse effects: Headache, arthralgias, fatigue, asthenia, dizziness, hypertension, oedema, chest pain, nausea, vomiting, diarrhoea. renal failure and were being treated with subcutaneous injections. It is now recommended that people on haemodialysis receive the drug intravenously rather than subcutaneously. If the drug is started and there is no response, or if a person fails to maintain a response, the dose should not be increased, and red blood cell aplasia should be suspected. The person should be evaluated with the appropriate tests and supported. A target haemoglobin of no more than 12 g/dL is sought when using these drugs. Higher levels have been associated with cardiovascular events, including death, and increased rates of tumour progression death in people with cancer in whom the drug was being used to treat anaemia associated with toxic drug therapy. Monitoring the haemoglobin levels is critical for safe and therapeutic use of the erythropoiesis-stimulating agents. An increase in tumour growth was also found in people with cancer treated with these drugs when haemoglobin levels were not kept within the guidelines of no more than 12 g/dL. This has been added to the warnings for these drugs to alert caregivers to carefully monitor haemoglobin levels to assure safety.

Oxygen use in tissues

Arterial oxygen pressure

Erythropoietin

Stimulation for erythropoietin from kidney

Stem cell stimulation

Arterial oxygen pressure

RBCs formed

O 2 carrying capacity

FIGURE 49.3  Erythropoiesis controls the rate of blood cell production.

Adverse effects The adverse effects most commonly associated with these drugs include the CNS effects of headache, fatigue, asthenia and dizziness and the potential for serious seizures. These effects may be the result of a cellular response to the glycoprotein. Nausea, vomiting and diarrhoea are also common effects. Cardio­ vascular symptoms can include hypertension, oedema and possible chest pain, all of which may be related to the increase in RBC numbers changing the balance within the cardiovascular system. People receiving intravenous administration must also be monitored In late 2005, the makers of epoetin and darbepoetin sent out warning letters to healthcare professionals to bring attention to serious adverse effects that had been noted in post-marketing studies. Cases of pure red cell aplasia (defective or insufficient production) and severe anaemias, with or without cytopenias (decreased levels of other blood cells), had been reported. These cases were associated with the development of neutralising antibodies to erythropoietin. Use of any therapeutic protein brings with it the risk of antibody production. All of the erythropoietic proteins (Aranesp, Eprex) now carry a warning about the potential for this problem. If a person is being treated with one of these drugs and develops a sudden loss of response accompanied by severe anaemia and low reticulocyte count, they should be assessed for the possible causes. Assays for binding and neutralising antibodies should be done. If an antibody-mediated anaemia is confirmed, the drug should be permanently stopped and the person should not be switched to another erythropoietic protein because cross-reaction could occur. Most of the people in the reported cases had chronic Safe medication administration