McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

TABLE 49.1

DRUGS IN FOCUS Erythropoiesis-stimulating agents

Drug name

Dosage/route

Usual indications

darbepoetin alfa (Aranesp)

0.45 mcg/kg IV or SC once per week; 2.25 mcg/kg per week SC (with chemotherapy)

Treatment of anaemia associated with chronic renal failure, including people on dialysis; treatment of chemotherapy- induced anaemia Treatment of anaemia associated with renal failure and people on dialysis; reduction in need for people undergoing surgical procedures; treatment of anaemia associated with AIDS therapy; treatment of anaemia associated with cancer chemotherapy Treatment of anaemia associated with chronic renal failure, individuals with non-myeloid malignancy, or to augment autologous blood transfusion Treatment of anaemia associated with chronic renal failure, individuals with non-myeloid malignancy, or to augment autologous blood transfusion Treatment of anaemia associated with chronic renal failure, including people undergoing dialysis treatment

50–100 units/kg IV or SC three times per week; 300 units/kg per day SC for 15 days (reduction of need for blood transfusions)

epoetin alfa (Eprex)

epoetin beta (NeoRecormon)

60 units/kg SC or 120 units/kg/week x 3 doses IV

epoetin lambda (Novicrit)

Elective surgery: 600 IU/kg SC weekly for 3 weeks; Autologous predonation program 300–600 IU/kg IV weekly for 3 weeks Chronic renal failure: 75–300 IU/kg IV weekly 0.6 mcg/kg SC once every 2 weeks; when desired haemoglobin level is reached, 1.2 mcg/kg SC once each month

methoxy polyethylene glycol-epoetin beta (Mircera)

Darbepoetin alfa is an erythropoietin-like protein produced in Chinese hamster ovary cells with the use of recombinant DNA technology. This drug gained negative publicity after it was used by athletes to increase their RBC count in the hope that it would give them more endurance and strength. Many athletic govern- ing bodies now screen for the presence of darbepoetin among other banned drugs. This drug has the advantage of once-weekly administration, compared with two to three times a week administration for epoetin. Methoxy polyethylene glycol-epoetin beta, the newest drug in this class, has the advantage of dosing once every 2 weeks or once a month. Both darbepoetin alfa and methoxy polyethylene glycol-epoetin beta are approved to treat anaemias associated with chronic renal failure, includ- ing people receiving dialysis. Darbepoetin alfa is also used for treatment of anaemia induced by cancer chemo- therapy. (See also Table 49.1.) Pharmacokinetics All of these drugs can be given IV or by subcutaneous injection. Epoetin alfa, which is like endogenous erythro- poietin, is metabolised in the serum through the normal process that the body uses to clear erythropoietin. It has a slow onset and peaks in 5 to 24 hours, and its duration of effect is usually 24 hours. It has a half-life of 4 to 13 hours and is excreted in the urine. Darbepoetin alfa has a half-life of 21 hours after intravenous administra- tion or 49 hours after subcutaneous administration. It

reaches peak effects in 14 hours (if given IV) or 34 hours (subcutaneously). Duration of effects is 24 to 72 hours and excretion is through the urine. Methoxy polyethyl- ene glycol-epoetin beta has a half-life of 67 hours. It has a slow onset and reaches peak effects in 48 to 72 hours. It is also cleared in the serum and excreted in the urine. It is not known whether epoetin alfa or methoxy poly­ ethylene glycol-epoetin enters breast milk; however, darbepoetin alfa does cross into breast milk. Contraindications and cautions All three of these drugs are contraindicated in the presence of uncontrolled hypertension because of the risk of even further hypertension when RBC numbers increase and the pressure within the vascular system also increases ; with known hypersensitivity to any component of the drug to avoid hypersensitivity reac- tions ; and with breastfeeding because of the potential for allergic-type reactions with the neonate. There are no adequate studies in pregnancy, and so use should be limited to those situations in which the benefit to the mother clearly outweighs the potential risk to the fetus. Use caution when administering any of these drugs to people with normal renal functioning and adequate levels of erythropoietin because of the rebound decrease in erythropoietin that will occur and when administer- ing them to a person with anaemia and normal renal function because this can cause more severe anaemia (see Figure 49.3).