Page 619 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 33 Agents Used in Cytopenias; Hematopoietic Growth Factors 605

are observed in 2–6 hours and the half-life is 26–35 hours. chemotherapy. Interleukin-11 is given by subcutaneous injec-
Eltrombopag is excreted primarily in the feces. tion at a dose of 50 mcg/kg daily. It is started 6–24 hours after
completion of chemotherapy and continued for 14–21 days or
Pharmacodynamics until the platelet count passes the nadir and rises to more than
50,000 cells/μL.
Interleukin-11 acts through a specific cell surface cytokine recep- In patients with chronic immune thrombocytopenia who
tor to stimulate the growth of multiple lymphoid and myeloid failed to respond adequately to previous treatment with steroids,
cells. It acts synergistically with other growth factors to stimulate immunoglobulins, or splenectomy, romiplostim and eltrombopag
the growth of primitive megakaryocytic progenitors and, most significantly increase platelet count in most patients. Both drugs
importantly, increases the number of peripheral platelets and are used at the minimal dose required to maintain platelet counts
neutrophils. of greater than 50,000 cells/μL.
Romiplostim has high affinity for the human Mpl receptor.
Eltrombopag interacts with the transmembrane domain of the Toxicity
Mpl receptor. Both drugs induce signaling through the Mpl recep-
tor pathway and cause a dose-dependent increase in platelet count. The most common adverse effects of IL-11 are fatigue, headache,
Romiplostim is administered once weekly by subcutaneous injec- dizziness, and cardiovascular effects. The cardiovascular effects
tion. Eltrombopag is an oral drug. For both drugs, peak platelet include anemia (due to hemodilution), dyspnea (due to fluid
count responses are observed in approximately 2 weeks. accumulation in the lungs), and transient atrial arrhythmias.
Hypokalemia also has been seen in some patients. All of these
adverse effects appear to be reversible.
Clinical Pharmacology Eltrombopag is potentially hepatotoxic and liver function must
Interleukin-11 is approved for the secondary prevention of be monitored, particularly when used in patients with hepatitis C.
thrombocytopenia in patients receiving cytotoxic chemotherapy Portal vein thrombosis also has been reported with eltrombopag and
for treatment of nonmyeloid cancers. Clinical trials show that it romiplostim in the setting of chronic liver disease. In patients with
reduces the number of platelet transfusions required by patients myelodysplastic syndromes, romiplostim increases the blast count
who experience severe thrombocytopenia after a previous cycle and risk of progression to acute myeloid leukemia. Marrow fibrosis
of chemotherapy. Although IL-11 has broad stimulatory effects has been observed with thrombopoietin agonists but is generally
on hematopoietic cell lineages in vitro, it does not appear to have reversible when the drug is discontinued. Rebound thrombocytope-
significant effects on the leukopenia caused by myelosuppressive nia has been observed following discontinuation of TPO agonists.

SUMMARY Agents Used in Anemias and Hematopoietic Growth Factors

Mechanism of Clinical Pharmacokinetics, Toxicities,
Subclass, Drug Action Effects Applications Interactions
IRON
• Ferrous sulfate Required for Adequate supplies Iron deficiency, which manifests as Complicated endogenous system for
biosynthesis of heme required for normal microcytic anemia • oral absorbing, storing, and transporting iron
and heme-containing heme synthesis preparation • Toxicity: Acute overdose results in
proteins, including • deficiency results in necrotizing gastroenteritis, abdominal pain,
hemoglobin and inadequate heme bloody diarrhea, shock, lethargy, and
myoglobin production dyspnea • chronic iron overload results in
hemochromatosis, with damage to the
heart, liver, pancreas, and other organs
• organ failure and death can ensue

• Ferrous gluconate and ferrous fumarate: Oral iron preparations
• Iron dextran, iron sucrose complex, sodium ferric gluconate complex, ferric carboxymaltose, and ferumoxytol: Parenteral preparations can cause pain, hypersensitivity
reactions
IRON CHELATORS
• Deferoxamine (see Chelates excess iron Reduces toxicity Acute iron poisoning; inherited or Preferred route of administration is IM or SC
also Chapters 57 associated with acute acquired hemochromatosis • Toxicity: Rapid IV administration may cause
and 58) or chronic iron overload hypotension • neurotoxicity and increased
susceptibility to certain infections have
occurred with long-term use
• Deferasirox: Orally administered iron chelator for treatment of hemochromatosis
(continued)