plerixafor


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plerixafor

(ple-rix-a-fore) ,

Mozobil

(trade name)

Classification

Therapeutic: none assigned
Pharmacologic: hematopoietic stem cell mobilizers
Pregnancy Category: D

Indications

Mobilizes hematopoietic stem cells to peripheral blood for collection and use in autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma; used in combination with granulocyte-colony stimulation factor (G-CSF).

Action

Inhibits the CXCR-4 chemokine receptor, blocking it's binding ability. Inhibition decreases adherence of stem cells to bone marrow, freeing them up to mobilize to peripheral blood.

Therapeutic effects

Mobilization of stem cells to peripheral blood allowing collection.

Pharmacokinetics

Absorption: Well absorbed following subcut administration.
Distribution: Largely confined to extravascular fluid space.
Metabolism and Excretion: Not metabolized by the liver; 70% unchanged in urine.
Half-life: 5.3 hr.

Time/action profile (mobilization of cells)

ROUTEONSETPEAKDURATION
Subcutrapid10–14 hr*unknown
*With G-CSF pretreatment.

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Leukemia; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Renal impairment (dose ↓ required if CCr ≤50 mL/min); Geriatric: Consider age-related ↓ in renal function and greater sensitivity to drug effects; Obstetric: Women with child-bearing potential; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia

Gastrointestinal

  • splenic rupture (life-threatening)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal distention/pain
  • constipation
  • dry mouth
  • dyspepsia
  • flatulence

Dermatologic

  • erythema
  • sweating

Hematologic

  • leukemia/tumor cell mobilization
  • thrombocytopenia

Local

  • injection site reactions (most frequent)

Musculoskeletal

  • musculoskeletal pain

Neurologic

  • oral hypoesthesia

Miscellaneous

  • anaphylaxis (life-threatening)

Interactions

Drug-Drug interaction

None noted.

Route/Dosage

Subcutaneous (Adults) Following pretreatment with G-CSF for 4 days—0.24 mg/kg once daily for up to 4 days (not to exceed 40 mg/day); use actual body weight to calculate dose.

Renal Impairment

Subcutaneous (Adults) Following pretreatment with G-CSF for 4 days—0.16 mg/kg once daily for up to 4 days (not to exceed 27 mg/day).

Availability

Solution for subcutaneous injection: 20 mg/mL

Nursing implications

Nursing assessment

  • Assess for splenic enlargement and potential rupture (left upper abdominal pain and/or scapular or shoulder pain) periodically during therapy.
  • Monitor for signs and symptoms of anaphylaxis (urticaria, periorbital swelling, dyspnea, hypoxia) during and for at least 30 min following administration. Discontinue therapy and treat symptomatically if symptoms occur.
  • Lab Test Considerations: Monitor WBC and platelets during therapy. May cause leukocytosis and thrombocytopenia.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Begin therapy after patient has received 4 days of G-CSF daily and approximately 11 hrs prior to initiation of apheresis.
  • Subcutaneous: Administer subcut daily for 4 days. Do not use solutions that are discolored or contain a precipitate. Vials are single use; discard any unused medication.

Patient/Family Teaching

  • Explain purpose of medication to patient.
  • Advise patient to report signs and symptoms of potential systemic reactions (urticaria, periorbital swelling, dyspnea, hypoxia) to health care professional.
  • Instruct patient to notify health care professional immediately if vasovagal reactions (orthostatic hypotension, syncope) occur during or shortly after injection.
  • Advise patient to notify health care professional if itching, rash, or reactions at injection site occur; may be treated with OTC medications.
  • May cause GI disorders including diarrhea, nausea, vomiting, flatulence, and abdominal pain. Advise patient to notify health care professional if GI disorders are severe.
  • Plerixafor is teratogenic. Caution female patients to use effective contraception during therapy and to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Increase in CD34+ cells/kg in peripheral blood prior to aphresis.
References in periodicals archive ?
The Phase 1 study will investigate the safety and tolerability of MGTA-145 alone and in combination with plerixafor in healthy volunteers and establish recommended Phase 2 doses as well as measure the number of hematopoietic stem cells in the blood after dosing with MGTA-145 alone and in combination with plerixafor.
MGTA-145 works synergistically with plerixafor, another stem cell mobilization product.
LOW-DOSE TREATMENT with plerixafor, a CXC chemokine receptor 4 antagonist, was well tolerated and markedly improved severe presentations of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome in three patients who could not receive granulocyte colony-stimulating factor (G-CSF) therapy.
The cancer drug, plerixafor, stimulates the immune system to release more of a certain stem cell (hematopoietic progenitor cells, or Hematopoietic progenitor cells (HPCs)) from the bone marrow into the bloodstream.
His myeloma subsequently relapsed and stem cells were collected with filgrastim and plerixafor mobilization.
Finally, there are data describing the superior effects of some new agents in combination with G-CSF, such as plerixafor or mozobil (antagonist of the alpha chemokine receptor CXCR4) in mobilizing the CD[34.sup.+] cells - including the immature SCs, capable for durable or late (long-term) BM repopulation with following hematopoietic reconstitution [2, 14].
Mobilization of stem cells from the bone marrow also has great therapeutic potential.[sup][37] Plerixafor (also known as age-related macular degeneration (AMD)-3100, an inhibitor of CXCR4) significantly increased vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2)-positive cells in the peripheral blood, elevated SDF-1 levels, and promoted blood vessel formation in an ischemic flap model.
Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.
Plerixafor is a small molecule antagonist that inhibits the binding interaction of stromal cell-derived factor-1 (SDF-1) to the chemokine receptor, CXCR4 [1, 68].
Jeanblanc et al., "Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model," Cytotherapy, vol.
However, when G-CSF was administrated in conjunction with plerixafor, an antagonist of the SDF-1/CXCR4 axis, the mobilization ability of stem cells was observed to be restored [48, 50].