Plerixafor Drug Information

Plerixafor injection is indicated in combination with filgrastim to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) or multiple myeloma (MM).

Recommended Dosage and Administration

Begin treatment with plerixafor injection after the patient has received filgrastim once daily for 4 days. Administer plerixafor injection approximately 11 hours prior to initiation of each apheresis for up to 4 consecutive days. The recommended dose of plerixafor injection by subcutaneous injection is based on body weight: 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing less than or equal to 83 kg. 0.24 mg/kg of body weight for patients weighing greater than 83 kg Use the patient’s actual body weight to calculate the volume of plerixafor injection to be administered.

Each vial delivers 1.2 mL of 20 mg/mL solution, and the volume to be administered to patients should be calculated from the following equation: 0.012 × patient’s actual body weight (in kg) = volume to be administered (in mL) In clinical studies, plerixafor injection dose has been calculated based on actual body weight in patients up to 175% of ideal body weight. Plerixafor injection dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated. Based on increasing exposure with increasing body weight, the plerixafor injection dose should not exceed 40 mg/day.

Vials should be inspected visually for particulate matter and discoloration prior to administration and should not be used if there is particulate matter or if the solution is discolored. Discard unused portion.

Recommended Concomitant Medications

Administer daily morning doses of filgrastim 10 mcg/kg for 4 days prior to the first evening dose of plerixafor injection and on each day prior to apheresis.

Dose Modifications in Renal Impairment

In patients with moderate and severe renal impairment (estimated creatinine clearance (CL CR ) less than or equal to 50 mL/min), reduce the dose of plerixafor injection by one-third based on body weight category as shown in Table 1. If CL CR is less than or equal to 50 mL/min the dose should not exceed 27 mg/day, as the mg/kg-based dosage results in increased plerixafor exposure with increasing body weight. Similar systemic exposure is predicted if the dose is reduced by one-third in patients with moderate and severe renal impairment compared with subjects with normal renal function.

Table 1: Recommended Dosage of Plerixafor Injection in Patients with Renal Impairment The following (Cockcroft-Gault) formula may be used to estimate CL CR: Males: Creatinine clearance (mL/min) = weight (kg) × (140 – age in years) 72 × serum creatinine (mg/dL) Females: Creatinine clearance (mL/min) = 0.85 × value calculated for males There is insufficient information to make dosage recommendations in patients on hemodialysis.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥10%) reported in patients who received plerixafor in conjunction with filgrastim regardless of causality and more frequent with plerixafor than placebo during HSC mobilization and apheresis were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting. Safety data for plerixafor in combination with filgrastim were obtained from two randomized placebo-controlled studies (301 patients) and 10 uncontrolled studies (242 patients).

Patients were primarily treated with plerixafor at daily doses of 0.24 mg/kg subcutaneous. Median exposure to plerixafor in these studies was 2 days (range 1 to 7 days). In the two randomized studies in patients with NHL and MM, a total of 301 patients were treated in the plerixafor and filgrastim group and 292 patients were treated in the placebo and filgrastim group.

Patients received daily morning doses of filgrastim 10 mcg/kg for 4 days prior to the first dose of plerixafor 0.24 mg/kg subcutaneous or placebo and on each morning prior to apheresis. The adverse reactions that occurred in ≥5% of the patients who received plerixafor regardless of causality and were more frequent with plerixafor than placebo during HSC mobilization and apheresis are shown in Table 2. Table 2: Adverse Reactions in ≥5% of Non-Hodgkin’s Lymphoma and Multiple Myeloma Patients Receiving Plerixafor and More Frequent than Placebo during HSC Mobilization and Apheresis % of patients with NHL or MM had mild to moderate injection site reactions at the site of subcutaneous administration of plerixafor.

These included erythema, hematoma, hemorrhage, induration, inflammation, irritation, pain, paresthesia, pruritus, rash, swelling, and urticaria. Mild to moderate allergic reactions were observed in less than 1% of patients within approximately 30 min after plerixafor administration, including one or more of the following: urticaria (n=2), periorbital swelling (n=2), dyspnea (n=1) or hypoxia (n=1). Symptoms generally responded to treatments (e.g., antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously.

Vasovagal reactions, orthostatic hypotension, and/or syncope can occur following subcutaneous injections. In plerixafor oncology and healthy volunteer clinical studies, less than 1% of subjects experienced vasovagal reactions following subcutaneous administration of plerixafor doses ≤0.24 mg/kg. The majority of these events occurred within 1 hour of plerixafor administration.

Because of the potential for these reactions, appropriate precautions should be taken. Other adverse reactions in the randomized studies that occurred in <5% of patients but were reported as related to plerixafor during HSC mobilization and apheresis included abdominal pain, hyperhidrosis, abdominal distention, dry mouth, erythema, stomach discomfort, malaise, hypoesthesia oral, constipation, dyspepsia, and musculoskeletal pain. Hyperleukocytosis: In clinical trials, white blood cell counts of 100,000/mcL or greater were observed, on the day prior to or any day of apheresis, in 7% of patients receiving plerixafor and in 1% of patients receiving placebo.

No complications or clinical symptoms of leukostasis were observed.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been reported from postmarketing experience with plerixafor. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System: Splenomegaly and splenic rupture Immune System Disorders: Anaphylactic reactions, including anaphylactic shock Psychiatric Disorders: Abnormal dreams and nightmares

Pregnancy Risk Summary Limited available data with plerixafor use in pregnant women are insufficient to inform a drug- associated risk of adverse developmental outcomes. In animal reproduction studies, subcutaneous administration of plerixafor to pregnant rats during organogenesis at doses 10­-times the maximum recommended human doses resulted in embryo-fetal mortality, structural abnormalities, and alterations to growth. Advise pregnant women of the potential risk to the fetus.

Advise women of reproductive potential to avoid becoming pregnant while receiving treatment with plerixafor. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The background risk of major birth defects and miscarriages for the indicated population is unknown. Data Animal data Plerixafor administered to pregnant rats induced embryo-fetal toxicity, including fetal death, increased resorptions and postimplantation loss, decreased fetal weights, anophthalmia, shortened digits, cardiac interventricular septal defect, ringed aorta, globular heart, hydrocephaly, dilatation of olfactory ventricles, and retarded skeletal development.

Pediatric Use The safety and effectiveness of plerixafor have not been established in pediatric patients. Effectiveness was not demonstrated in a single phase 1/2 randomized, open-label, comparative study of plerixafor plus standard regimens for mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Forty-five pediatric patients ages 1 to <17 years with solid tumors or lymphoma were randomized 2:1 to plerixafor in addition to standard mobilization regimens (N=30) or standard mobilization regimens alone (N=15) (comparator arm).

No new safety signals were observed in pediatric patients in this trial.

Plerixafor injection is contraindicated in patients with a history of hypersensitivity to plerixafor. Anaphylactic shock has occurred with use of plerixafor. History of hypersensitivity to plerixafor.

Based on limited data at doses above the recommended dose of 0.24 mg/kg subcutaneous, the frequency of gastrointestinal disorders, vasovagal reactions, orthostatic hypotension, and/or syncope may be higher.