Chemical formula: C₂₈H₅₄N₈ Molecular mass: 502.782 g/mol PubChem compound: 65015
Plerixafor interacts in the following cases:
Patients with creatinine clearance 20-50 ml/min should have their dose of plerixafor reduced by one-third to 0.16 mg/kg/day. Clinical data with this dose adjustment are limited. There is insufficient clinical experience to make alternative posology recommendations for patients with a creatinine clearance <20 ml/min, as well as to make posology recommendations for patients on haemodialysis.
Based on increasing exposure with increasing body weight the dose should not exceed 27 mg/day if the creatinine clearance is lower than 50 ml/min.
Thrombocytopenia is a known complication of apheresis and has been observed in patients receiving plerixafor. Platelet counts should be monitored in all patients receiving plerixafor and undergoing apheresis.
Plerixafor has been uncommonly associated with potential systemic reactions related to subcutaneous injection such as urticaria, periorbital swelling, dyspnoea, or hypoxia. Symptoms responded to treatments (e.g., antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously. Cases of anaphylactic reactions, including anaphylactic shock, have been reported from world-wide post-marketing experience. Appropriate precautions should be taken because of the potential for these reactions.
There are no adequate data on the use of plerixafor in pregnant women. Based on the pharmacodynamic mechanism of action, plerixafor is suggested to cause congenital malformations when administered during pregnancy. Studies in animals have shown teratogenicity. Plerixafor should not be used during pregnancy unless the clinical condition of the woman requires treatment with plerixafor.
It is unknown whether plerixafor is excreted in human milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with plerixafor.
Women of childbearing potential have to use effective contraception during treatment.
The effects of plerixafor on male and female fertility are not known.
Plerixafor may influence the ability to drive and use machines. Some patients have experienced dizziness, fatigue or vasovagal reactions; therefore caution is advised when driving or operating machines.
Safety data for plerixafor in conjunction with G-CSF in oncology patients with lymphoma and multiple myeloma were obtained from 2 placebo-controlled Phase III studies (301 patients) and 10 uncontrolled Phase II studies (242 patients). Patients were primarily treated with daily doses of 0.24 mg/kg plerixafor by subcutaneous injection. The exposure to plerixafor in these studies ranged from 1 to 7 consecutive days (median = 2 days).
In the two Phase III studies in non-Hodgkin’s lymphoma and multiple myeloma patients (AMD3100-3101 and AMD3100-3102, respectively), a total of 301 patients were treated in the plerixafor and G-CSF group and 292 patients were treated in the placebo and G-CSF group. Patients received daily morning doses of G-CSF 10 g/kg for 4 days prior to the first dose of plerixafor or placebo and on each morning prior to apheresis. Adverse reactions that occurred more frequently with plerixafor and G-CSF than placebo and G-CSF and were reported as related in ≥1% of the patients who received plerixafor, during haematopoietic stem cell mobilisation and apheresis and prior to chemotherapy/ablative treatment in preparation for transplantation are shown in list below.
From chemotherapy/ablative treatment in preparation of transplantation through 12 months post-transplantation, no significant differences in the incidence of adverse reactions were observed across treatment groups.
Adverse reactions are listed by System Organ Class and frequency. Frequencies are defined according to the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Adverse reactions occurring more frequently with plerixafor than placebo and considered related to plerixafor during mobilisation and apheresis in phase III studies:
Not known: Splenomegaly, splenic rupture**
Uncommon: Allergic reaction* Anaphylactic reactions, including anaphylactic shock**
Common: Insomnia
Uncommon: Abnormal dreams, nightmares
Common: Dizziness, headache
Very common: Diarrhoea, nausea
Common: Vomiting, abdominal pain, stomach discomfort, dyspepsia, abdominal distention, constipation, flatulence, hypoaesthesia oral, dry mouth
Common: Hyperhidrosis, erythema
Common: Arthralgia, musculoskeletal pain
Very common: Injection and infusion site reactions
Common: Fatigue, malaise
* The frequency of allergic reactions presented is based on adverse reactions that occurred in the oncology studies (679 patients). Events included one or more of the following: urticaria (n=2), periorbital swelling (n=2), dyspnoea (n=1) or hypoxia (n=1). These events were generally mild or moderate and occurred within approximately 30 min after plerixafor administration.
** From post-marketing experience
The adverse reactions reported in patients with lymphoma and multiple myeloma who received plerixafor in the controlled Phase III studies and uncontrolled studies, including a Phase II study of plerixafor as monotherapy for haematopoietic stem cell mobilisation, are similar. No significant differences in the incidence of adverse reactions were observed for oncology patients by disease, age, or gender.
In clinical studies, 7 of 679 oncology patients experienced myocardial infarctions after haematopoietic stem cell mobilisation with plerixafor and G-CSF. All events occurred at least 14 days after last plerixafor administration. Additionally, two female oncology patients in the compassionate use programme experienced myocardial infarction following haematopoietic stem cell mobilisation with plerixafor and G-CSF. One of these events occurred 4 days after last plerixafor administration. Lack of temporal relationship in 8 of 9 patients coupled with the risk profile of patients with myocardial infarction does not suggest plerixafor confers an independent risk for myocardial infarction in patients who also receive G-CSF.
White blood cell counts of 100 × 109/L or greater were observed, on the day prior to or any day of apheresis, in 7% patients receiving plerixafor and in 1% patients receiving placebo in the Phase III studies. No complications or clinical symptoms of leukostasis were observed.
In plerixafor oncology and healthy volunteer clinical studies, less than 1% of subjects experienced vasovagal reactions (orthostatic hypotension and/or syncope) following subcutaneous administration of plerixafor doses ≤0.24 mg/kg. The majority of these events occurred within 1 hour of plerixafor administration.
In plerixafor clinical studies of oncology patients, there have been rare reports of severe gastrointestinal events, including diarrhoea, nausea, vomiting, and abdominal pain.
Paraesthesia is commonly observed in oncology patients undergoing autologous transplantation following multiple disease interventions. In the placebo-controlled Phase III studies, the incidence of paraesthesia was 20.6% and 21.2% in the plerixafor and placebo groups, respectively.
In the two placebo-controlled clinical studies of plerixafor, 24% of patients were ≥65 years old. No notable differences in the incidence of adverse reactions were observed in these elderly patients when compared with younger ones.
Thirty patients were treated with 0.24 mg/kg of plerixafor in an open label, multicenter, controlled study (DFI 12860). The safety profile in this paediatric study was consistent with what has been observed in adults.
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