Plerixafor is a class of drugs called hematopoietic stem cell mobilizer. When combined with filgrastim, a colony stimulating factor, it mobilizes CD-34 positive cells that have repopulating capabilities.
Indications of Plerixafor:
It is a used to mobilize hematopoietic cells (HSCs) which are then used for collection and subsequent autologous transfer (in combination with filgrastim), in patients with non-Hodgkin lymphoma and multiple myeloma
Mechanism of Action (MOA) of Plerixafor:
Plerixafor inhibits the binding of stromal-cell-derived factor-1a (SDF-1a), which is expressed on bone-marrow stromal cells to the CXC chemical receptor 4 (CXCR4). This results in mobilization and transfer of hematopoietic stem cells and progenitor cells into peripheral blood. Combining Plerixafor with filgrastim results is a synergistic rise in CD34+ cell mobilization. Mobilized CD34+ cells can engraft with extended repopulating capabilities.
Onset and duration of action of Plerixafor:
Peak CD34+ mobilisation in healthy volunteers occurs in 6 to 9 hours after administration when plerixafor is used as monotherapy. When plerixafor is used in combination with filgrastim, it takes 10-14 hours for the peak effect to be seen.
The duration of action, manifested by a sustained elevation of CD34 positive cells is about 4 to 18 hours in healthy volunteers.
Absorption is rapid when the drug is administered subcutaneously. Fixed dosing (20mg) results in a higher dose than the mg/kg dose but the median time it takes to reach the target cells count is the same for both regimens
58% or less of the drug is protein-bound. It is not metabolized and has a terminal half-life elimination of about 3 to 5 hours. The time to reach peak plasma concentration is 30 to 60 minutes when administered subcutaneously.
70% of the drug is excreted via urine. Clearance is decreased in patients with impaired renal function. Patients with mild renal impairment had an increase of 7% (CrCl 51-80 mL/minute), 32% with moderate renal impairment (CrCl 31-50 mL/minute) and 39% with severe kidney impairment (CrCl >31 mL/minute).
How much does Plerixafor cost?
In US Mozobil injection 24 mg/1.2 mL costs $8,855.47 per ml.
How is Plerixafor administered?
It is administered into the skin (SubQ). Apply subcutaneously at least 11 hours before initiation of apheresis. Some clinical trials showed that plerixafor administration was initiated on the night before apheresis.
Filgrastim was started on day 1 and apheresis began on day 5. On day 5, filgrastim and plerixafor were both administered in the evening. Apheresis was then initiated in the morning on the day 5. With filgrastim and plerixafor, daily apheresis was continued until adequate cell collection is achieved.
How should Plerixafor be handled?
Take all precautions when handling, handling, administering, and disposing of your items. Single gloves should be worn when receiving, unpacking and storing.
NIOSH recommends double gloving and a protective garment. Administration requires double gloving and protection. To determine the best containment strategy, assess risk.
Plerixafor dosing in Adults:
Note that Dosing will be based on body weight. After 4 days of filgrastim treatment, begin plerixafor. Plerixafor, filgrastim and apheresis must be continued daily until adequate cell collection is achieved, with a maximum of 4 days.
Plerixafor dose in hematopoietic stem cells mobilization (in nonHodgkin lymphoma or multiple myeloma).
Administer SubQ 11hrs prior to apheresis
Patients under 83 kg:
- 20mg fixed dose or 0.24mg/kg daily for up to four consecutive days
Patients over 83kg:
- 0.24 mg/kg daily, for maximum 40 mg per day
Plerixafor Dose in adults with Renal Impairment:
Note: Creatinine clearance estimates based on Cockcroft–Gault formula
- CrCl >50 mL/minute:
- No dosage adjustment necessary.
- CrCl < 50 mL/minute
- Patients <=83 kg:
- 13 mg fixed dose or 0.16 mg/kg once daily
- Patients over 83 kg or 160kg:
- 0.16 mg/kg daily; maximum dosage: 27 mg daily
- Patients <=83 kg:
- Hemodialysis:
- The manufacturer’s label does not contain any dosage adjustments (has not yet been tested).
Plerixafor Dose in adults with Hepatic Impairment:
- The manufacturer’s labeling does not include any dosage adjustments.
Plerixafor dose in Obese individuals:
Manufacturer recommends that patients who weigh up to 175% of their ideal body weight should calculate the dose using actual weight (maximum daily dose 40 mg). Patients with a body mass greater than 175% have not been tested.
Contraindications to Plerixafor Use:
Anaphylactic shock (hypersensitivity to plerixafor and any component of the formulation) has been reported in the past.
Warnings and Precautions
Anaphylactic shock and hypersensitivity:
- Serious hypersensitivity reactions, including anaphylactic-type reactions (may be life-threatening with serious hypotension and shock) have been reported. Monitor patients for signs of hypersensitivity for at least 30 minutes following administration. Continue monitoring them until they are clinically stable. You should immediately have medication, staff, and equipment to manage hypersensitivity. Sometimes mild-to-moderate allergic reactions can also occur within 30 minutes.
Hematologic effects:
- Use filgrastim in combination with it to increase the number of circulating leukocytes. Monitor WBC counts. Thrombocytopenia was observed. Monitor platelet counts.
Splenic enlargement/rupture:
- When plerixafor is used with filgrastim, cases of splenomegaly or splenic rupture have been reported. Instruct patients to report pain in the left upper quadrant or shoulder/scapular area; immediately evaluate any patient who reports these symptoms.
Leukemia:
- Not for patients with leukemia. May contaminate the apheresis product if leukemic cells are mobilized.
Concurrent drug treatment issues:
- Nephrotoxic drugs: Medicines that reduce renal function or compete with active tubular secretion can increase serum levels of plerixafor.
Other warnings/precautions:
- Tumor cell mobilization: If used with filgrastim, tumor cells from the marrow can be extracted in leukapheresis products. The potential effects of tumor cell reinfusion are unknown.
Side effects of Plerixafor (Mozobil):
Common adverse drug reactions (>10%)
Less common side effects (1% to 10%):
Reproductive considerations while using Mozobil:
Before using females with reproductive potential, it is important to determine if you are pregnant. Therapy should not be used if you are pregnant. Treatment should be continued for at least one week by females with reproductive potential.
According to animal reproduction studies, in-utero exposure of plerixafor could cause harm to fetal health. It is unknown if plerixafor can be found in breast milk. The manufacturer doesn’t recommend breastfeeding during therapy, or for more than one week after the last dose.
Monitoring Parameters while using mozobil:
Monitor CBC with differential, platelets, and monitor for signs/symptoms associated with hypersensitivity for up to 30 minutes following administration and until clinically stable.
Before using females with reproductive potential, it is important to determine if you are pregnant.