Plerixafor (Mozobil)

Plerixafor (Mozobil) Uses:

• Peripheral stem cell mobilization:
  • It is indicated in combination with filgrastim to mobilize hematopoietic stem cells (HSCs) for collection and subsequent autologous transplantation in patients with multiple myeloma and non-Hodgkin lymphoma.

Plerixafor (Mozobil) Dose in Adults

Note:

• The actual body weight is used for calculating the dose. The treatment is initiated after the patient has received filgrastim (see "how to administer Tab below")
• The treatment is continued until sufficient cells are collected or up to a maximum of four days.

Plerixafor (Mozobil) Dose in the treatment of hematopoietic stem cell mobilization in non-Hodgkin lymphoma and multiple myeloma):

• Administer the drug subcutaneously about 11 hours before apheresis. (See below "How to administer Tab")
  • Patients ≤83 kg:
    • 20 mg fixed-dose or 0.24 mg/kg once a day for up to four consecutive days
  • Patients >83 kg:
    • 24 mg/kg once a day for up to four consecutive days.
    • The maximum dose is 40 mg daily.

Use in children:

The safety and efficacy of the drug in children have not been established.   

Pregnancy Risk Category: D

• It is important to avoid pregnancy during treatment, as animal reproduction studies have shown fetal harm.
• Before treatment begins, pregnant women with reproductive potential should have their pregnancy tested. The treatment should be continued for at least one week.

Use Plerixa during breastfeeding

• It is unknown if the breastmilk contains any of this substance.
• The manufacturer suggests that breastfeeding mothers avoid the drug for at least one week because of the risk of serious adverse reactions.

Mozobil Dose in Kidney Disease:

Note: Creatinine clearance estimate based on Cockcroft-Gault formula:

• CrCl greater than 50 mL/minute:
  • Adjustment in the dose is not necessary.
• CrCl of 50 mL/minute or less:
  • Patients ≤83 kg:
    • 13 mg fixed-dose or 0.16 mg/kg once a day
  • Patients >83 kg and <160 kg:
    • 0.16 mg/kg once a day
    • The maximum daily dose is 27 mg.
• Hemodialysis:
  • The manufacturer has not recommended any adjustments in the dose.
  • It has not been studied in patients on hemodialysis.

Dose in Liver disease:

The manufacturer has not recommended any adjustment in the dose in patients with liver disease.   

Common Side Effects of Plerixafor (Mozobil):

• Central Nervous System:
  • Fatigue
  • Headache
  • Dizziness
• Gastrointestinal:
  • Diarrhea
  • Nausea
• Local:
  • Injection Site Reaction Including
    • Edema
    • Erythema
    • Hematoma
    • Hemorrhage
    • Induration
    • Inflammation
    • Irritation
    • Pain
    • Paresthesia
    • Pruritus
    • Skin Rash
    • Urticaria)
• Neuromuscular & Skeletal:
  • Arthralgia

Less Common Side Effects Of Plerixafor (Mozobil):

• Central Nervous System:
  • Insomnia
  • Malaise
• Dermatologic:
  • Erythema
  • Hyperhidrosis
• Gastrointestinal:
  • Vomiting
  • Flatulence
  • Abdominal Distension
  • Abdominal Distress
  • Abdominal Pain
  • Constipation
  • Dyspepsia
  • Oral Hypoesthesia
  • Xerostomia
• Hematologic & Oncologic:
  • Hyperleukocytosis
• Neuromuscular & Skeletal:
  • Musculoskeletal Pain

Contraindication to Plerixafor (Mozobil):

History of allergic reactions to plerixafor or any component of the formulation.

Warnings and Precautions

• Hypersensitivity and anaphylactic shock:
  • Anaphylactic-type reactions and severe allergic reactions can occur. Hypotension and shock may occur in patients, which can be potentially life-threatening.
  • Patients must be monitored for any hypersensitivity reactions 30 minutes after drug administration and until they are clinically stable.
  • Hypersensitivity reactions can be treated at the spot.
  • Some patients may experience mild or moderate allergic reactions within 30 min after the drug is administered.
• Hematologic effects
  • When filgrastim is combined with it, patients may develop leukocytosis. It is important to monitor the leukocyte count.
  • Thrombocytopenia may occur. Keep an eye on platelet counts.
• Splenic enlargement, and rupture
  • Use of filgrastim in combination with it can lead to splenomegaly or splenic rupture.
  • Patients should be instructed to immediately report any pain in their left upper abdomen, scapula or tip of the shoulders. 
  • Patients with symptoms of left upper abdominal pain should be seen immediately.
• Leukemia:
  • Patients with leukemia should not use it as contamination by leukemic cells could occur.
• Renal impairment
  • Patients with moderate-to severe renal impairment (CrCl =50mL/minute) should reduce their dose of the drug.

Monitoring parameters:

• CBC with differential and platelets;
• Observe for the clinical features of hypersensitivity reactions during the administration of the drug, for 30 minutes after its administration, and until the patient is clinically stable.
• Monitor the patient for splenomegaly
• Females of reproductive potential should have a pregnancy test done prior to treatment initiation.

How to administer Plerixafor (Mozobil)?

• It is intended for subcutaneous administration only.
• The drug is administered about 11 hours before the initiation of apheresis.
• Some experts suggest initiating filgrastim on day 1 and continuing it.
• On the evening of day 4, plerixafor treatment is initiated.
• Apheresis is done in the morning on day 5.
• The treatment and apheresis are continued until sufficient cells for autologous transplant are collected.   

Mechanism of action of Plerixafor (Mozobil):

• It reverses the binding of stromal-cell-derived factor-1a (SDF-1a), to the CXC Chemokine Receptor 4 (CXCR4), which is expressed on bone-marrow stromal and stromal cells.
• This allows for the mobilization progenitor stem cells and hematopoietic cells from bone marrow to the peripheral blood.
• It is also used in combination with filgrastim. 
• Combining the two can result in an increase in CD34+ cell mobilisation. 
• Mobilized CD34+ cells can engraft with extended repopulating capabilities.

The onset of action:

• Peak CD34+ mobilization in healthy volunteers) with Plerixafor monotherapy:
  • 6 to 9 hours after administration.
• Plerixafor + filgrastim:
  • 10 to 14 hours

Duration of action:

• Sustained elevation in CD34+ cells in healthy volunteers:
  • 4 to 18 hours after administration

Absorption following the subQ administration is rapid. The exposure of the drug increases with the bodyweight when using the mg/kg dosing. The fixed dosing of 20 mg results in a higher exposure of the drug than the mg/kg dose, but the median time to reach the target cell count is the same for both dosing regimens.

Protein binding:

• Less than 58%

Metabolism:

• It is not metabolized

The terminal half-life elimination of the drug:

• 3 to 5 hours

Time to peak plasma concentration after subcutaneous administration:

• 30 to 60 minutes

Excretion:

• About 70% of the drug is excreted in the urine as parent drug.

International Brands of Plerixafor:

• Mozobil
• Plerifor

Plerixafor Brand Names in Pakistan"

No Brands Available in Pakistan.