Biological Response Modifier Agents: Food and Drug Administration—Approved Drugs: Prescribing and Clinical Application Guidelines*
Recombinant Erythropoietin Epoetin alfa (Procrit), darbepoetin alfa (Aranesp)
HOW TO ADMINISTER
• Recombinant erythropoietin should not be shaken before it is drawn into a syringe because vigorous shaking can denature the glycoprotein, resulting in its being made biologically inactive.
• Recombinant erythropoietin should be administered as a SQ injection and not mixed with other solutions. In the case of IV administration, recombinant erythropoietin can be directly administered by an IV or venous dialysis port.
USE
PHARMACOKINETICS
USUAL DOSE AND SCHEDULE
Darbepoetin Alfa
Epoetin Alfa
• If hematocrit does not increase by week 8, increase dose by 25-50 units/kg TIW until maximum dose of 300 units/kg 3 × wk is achieved.
• 40,000 units as a single dose SQ every week
• If hematocrit does not rise by 5%-6% in 8 weeks, increase weekly dose to 60,000 units SQ every week.
• If no response, increase to a maximum 80,000 units SQ every week.
• Interrupt therapy if hematocrit levels exceed 40%, and resume at 75% of original dose when hematocrit returns to 36%.
COMPATIBILITY WITH OTHER DRUGS/INTRAVENOUS FLUIDS
Recombinant erythropoietin should not be mixed with other drugs or IV fluids for administration.
PATIENT EDUCATION
• Reinforce proper aseptic technique with self-administration.
• Reinforce adherence to dosing guidelines.
• Reinforce iron supplementation and potential bowel regimen to prevent constipation.
• Reinforce patient contact with health care professionals for side effect management and laboratory monitoring as necessary.
Filgrastim (Neupogen), Pegfilgrastim (Neulasta)
HOW TO ADMINISTER
PHARMACOKINETICS
COMPATIBILITY WITH OTHER DRUGS/INTRAVENOUS FLUIDS
• Do not mix with saline solution. Saline solution will cause the formation of a precipitate.
• Dilution with dextrose 5% solution should be accompanied by albuminization and should be administered from polyvinyl chloride, glass, or polyolefin IV bags to prevent absorption of plastic into the fluid.
• Pegfilgrastim should not be administered by the intravenous route.
PATIENT EDUCATION
• Monitor for flu-like symptoms of fever, nausea and vomiting, aching, and bone pain. Possible role for analgesics to control side effects
• Monitor for infection, fever, and injection site reactions.
• Avoid large crowds and persons with infections during therapy to prevent exposure while neutropenic.
• Ensure proper administration technique and adherence to prescribed regimen.
Sargramostim (Leukine)
PRETREATMENT GUIDELINES
• Baseline complete blood cell count (CBC) with differential, liver function panel, renal function, and weight and hydration status should be assessed before initiation of therapy with sargramostim.
• CBC should be monitored twice per week during therapy to detect excessive leukocyte production.
• Liver function tests should be monitored on a regular basis on patients with preexisting renal or hepatic dysfunction.
USE
Sargramostim has been Food and Drug Administration approved for use as follows:
• After induction chemotherapy in older patients with acute myelogenous leukemia to decrease the time to neutrophil recovery and decrease the risk of febrile neutropenia
• For mobilization of stem cells for leukapheresis collection and after transplantation of autologous cells to promote engraftment
• Myeloid reconstitution after autologous and allogeneic stem cell transplantation
• In transplant failure or engraftment delay to decrease the risk of infection from decreased neutrophil count
PHARMACOKINETICS
• IV administration: mean beta half-life in serum is measured at 60 minutes, with a peak concentration noted immediately after the completion of the infusion.
• SQ injection: mean beta half-life is 162 minutes after injection, with peak concentration measured at 1-3 hours and detectable levels out to 6 hours after injection.
USUAL DOSE AND SCHEDULE
PATIENT EDUCATION
• Instruct patient on proper injection technique: inject slowly over 1-2 minutes, do not manipulate injection site or rub after injection, ice site before and after injection, bring sargramostim to room temperature before injecting, use 5/8-inch 22-gauge needle for injection.
• Inform patient regarding first-dose reaction and advise that symptomatic support will be available. This is not a recurring event and does not constitute stopping therapy.
