Usage
Plerixafor is prescribed in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) to the peripheral blood. This mobilization is done for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). It is classified as a hematopoietic stem cell mobilizer.
Plerixafor works by reversibly blocking the CXCR4 chemokine receptor, which is involved in the binding of HSCs to the bone marrow stroma. By inhibiting CXCR4, plerixafor allows HSCs to be released from the bone marrow into the peripheral bloodstream, where they can be collected.
Alternate Names
- International Nonproprietary Name (INN): plerixafor
- Brand name: Mozobil
How It Works
Pharmacodynamics: Plerixafor antagonizes the CXCR4 receptor, leading to the release of HSCs from the bone marrow into the circulating blood. This increases the number of CD34+ cells, which are progenitor cells for various blood cell types.
Pharmacokinetics:
- Absorption: Following subcutaneous administration, plerixafor reaches peak plasma concentrations in approximately 30 to 60 minutes.
- Metabolism: Plerixafor is primarily excreted unchanged in the urine, with minimal hepatic metabolism.
- Elimination: The major elimination pathway is renal excretion. The terminal half-life ranges from 3 to 5 hours in healthy subjects and patients.
Mode of Action: Plerixafor binds reversibly to the CXCR4 chemokine receptor, thereby blocking the binding of its natural ligand, stromal cell-derived factor-1α (SDF-1α). This disruption releases HSCs from the bone marrow into the peripheral circulation.
Elimination Pathways: Plerixafor is primarily eliminated through renal excretion as the unchanged parent drug.
Dosage
Standard Dosage
Adults:
The standard dose is 0.24 mg/kg of body weight administered subcutaneously, not to exceed 40 mg/day. It is given approximately 11 hours prior to the start of each apheresis session. The treatment can be repeated for up to 4 consecutive days.
Children (1 to less than 18 years):
The recommended dose is 0.24 mg/kg of body weight administered subcutaneously, not to exceed 40 mg/day, approximately 6-11 hours prior to the initiation of apheresis. This is following a 4-day pretreatment with G-CSF. Further clinical trials are required to establish definite safety and efficacy in this population.
Special Cases:
- Elderly Patients: No dose adjustment is necessary in elderly patients with normal renal function. Dose adjustments are needed if creatinine clearance is ≤ 50 mL/min.
- Patients with Renal Impairment: If creatinine clearance is ≤ 50 mL/min, reduce the dose by one-third to 0.16 mg/kg, not to exceed 27 mg/day.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for patients with hepatic dysfunction.
- Patients with Comorbid Conditions: Care should be taken in dose selection for patients with comorbid conditions based on specific clinical scenarios.
Clinical Use Cases
Plerixafor is specifically indicated for HSC mobilization in patients with NHL and MM undergoing autologous stem cell transplantation. It is not indicated for use in other clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are necessary for patients with moderate to severe renal impairment (creatinine clearance ≤ 50 mL/min). No specific dose adjustments are required for hepatic impairment or other comorbid conditions, but careful clinical assessment is recommended.
Side Effects
Common Side Effects:
Diarrhea, nausea, vomiting, injection site reactions (pain, redness, swelling), fatigue, headache, dizziness, abdominal discomfort (bloating, gas), musculoskeletal pain, and insomnia.
Rare but Serious Side Effects:
Anaphylactic shock, serious hypersensitivity reactions, splenic enlargement and/or rupture (especially in patients receiving concomitant G-CSF), thrombocytopenia, tumor cell mobilization in patients with leukemia (not indicated for this population), and potential embryo-fetal toxicity.
Long-Term Effects:
Limited data are available on long-term effects of plerixafor.
Adverse Drug Reactions (ADR):
Anaphylactic shock, severe hypersensitivity reactions, and splenic rupture are serious ADRs that necessitate immediate medical attention.
Contraindications
Hypersensitivity to plerixafor is an absolute contraindication. Leukemia is a relative contraindication due to the potential for tumor cell mobilization.
Drug Interactions
Plerixafor has a low potential for drug interactions involving cytochrome P450 enzymes. It is not a substrate or inhibitor of P-glycoprotein. No clinically significant drug interactions have been observed in clinical trials.
Pregnancy and Breastfeeding
Plerixafor is a Pregnancy Category D drug. It can cause fetal harm and is teratogenic in animals. It should not be used during pregnancy unless the clinical benefit outweighs the potential risk.
It is unknown if plerixafor is excreted in human milk. Breastfeeding is not recommended during treatment and for one week after the final dose.
Drug Profile Summary
- Mechanism of Action: CXCR4 receptor antagonist, mobilizes HSCs.
- Side Effects: Diarrhea, nausea, injection site reactions, hypersensitivity reactions, splenic rupture.
- Contraindications: Hypersensitivity, Leukemia.
- Drug Interactions: Low potential.
- Pregnancy & Breastfeeding: Category D; not recommended.
- Dosage: 0.24 mg/kg SC (max 40 mg/day); renal impairment: reduce by 1/3.
- Monitoring Parameters: Complete blood counts (CBCs), including white blood cell and platelet counts, during treatment and apheresis; monitor for signs and symptoms of hypersensitivity reactions; assess for splenic enlargement; monitor renal function in patients with renal impairment.
Popular Combinations
Plerixafor is commonly used in combination with G-CSF for HSC mobilization. Rituximab can also be added to the regimen in patients with NHL.
Precautions
- Monitor for hypersensitivity reactions.
- Assess splenic integrity in patients reporting left upper abdominal pain and/or scapular/shoulder pain.
- Monitor platelet counts and WBCs.
- Use with caution in patients with renal impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Plerixafor?
A: 0.24 mg/kg SC (not to exceed 40 mg/day) approximately 11 hours before apheresis. Reduce dose to 0.16 mg/kg (not to exceed 27 mg/day) for patients with creatinine clearance ≤ 50 mL/min.
Q2: How does Plerixafor work?
A: It’s a CXCR4 chemokine receptor antagonist that mobilizes HSCs from the bone marrow into the peripheral blood.
Q3: What are the major side effects?
A: Diarrhea, nausea, injection site reactions, hypersensitivity, splenic rupture.
Q4: Can Plerixafor be used in patients with leukemia?
A: No, it is contraindicated in patients with leukemia due to the risk of mobilizing leukemic cells.
Q5: What are the key drug interactions?
A: Plerixafor has minimal drug interactions. It is not metabolized by CYP450 enzymes and is not a substrate or inhibitor of P-glycoprotein.
Q6: Can Plerixafor be used during pregnancy or breastfeeding?
A: No, it is contraindicated during pregnancy (Category D) and breastfeeding is not recommended.
Q7: What is the role of G-CSF in combination with Plerixafor?
A: G-CSF is given for 4 days prior to starting Plerixafor to enhance HSC mobilization.
Q8: How should Plerixafor be administered?
A: Subcutaneous injection.
Q9: What patient monitoring is required?
A: Monitor for hypersensitivity reactions during and after administration, complete blood counts (CBCs) including platelet counts, signs of splenic enlargement, and renal function (especially in patients with renal impairment).
Q10: What is the maximum daily dose of Plerixafor?
A: 40 mg/day for adults and children. 27 mg/day for patients with creatinine clearance ≤ 50 mL/min.
