Plerixadal^®

Adult patients

Plerixadal® is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in adult patients with lymphoma or multiple myeloma whose cells mobilise poorly.

Paediatric patients (1 to less than 18 years)

Plerixadal® is indicated in combination with G-CSF to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in children with lymphoma or solid malignant tumours, either:

• pre-emptively, when circulating stem cell count on the predicted day of collection after adequate mobilization with G-CSF (with or without chemotherapy) is expected to be insufficient with regards to desired hematopoietic stem cells yield, or
• who previously failed to collect sufficient haematopoietic stem cells.

• Hypersensitivity to the active substance or to any of the excipients listed in section 8.1. (smpc)

Tumour cell mobilisation in patients with lymphoma and multiple myeloma

When Plerixadal^® is used in conjunction with G-CSF for haematopoietic stem cell mobilisation in patients with lymphoma or multiple myeloma‚ tumour cells may be released from the marrow and subsequently collected in the leukapheresis product. Results showed that, in case tumour cells are mobilised, the number of tumour cells mobilised is not increased upon Plerixadal^® plus G-CSF compared to G-CSF alone.

Tumour cell mobilisation in leukaemia patients

In a compassionate use programme, Plerixadal^® and G-CSF have been administered to patients with acute myelogenous leukaemia and plasma cell leukaemia. In some instances, these patients experienced an increase in the number of circulating leukaemia cells. For the purpose of haematopoietic stem cell mobilisation, plerixafor may cause mobilisation of leukaemic cells and subsequent contamination of the apheresis product. Therefore, plerixafor is not recommended for haematopoietic stem cell mobilisation and harvest in patients with leukaemia.

Haematological effects

Hyperleukocytosis

Administration of Plerixadal^® in conjunction with G-CSF increases circulating leukocytes as well as haematopoietic stem cell populations. White blood cell counts should be monitored during Plerixadal® therapy. Clinical judgment should be exercised when administering Plerixadal® to patients with peripheral blood neutrophil counts above 50 x 10⁹/L.

Thrombocytopenia

Thrombocytopenia is a known complication of apheresis and has been observed in patients receiving Plerixadal^®. Platelet counts should be monitored in all patients receiving Plerixadal^® and undergoing apheresis.

Allergic reactions

Plerixadal^® 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.

Vasovagal reactions

Vasovagal reactions, orthostatic hypotension, and/or syncope can occur following subcutaneous injections. Appropriate precautions should be taken because of the potential for these reactions.

Effect on the spleen

In preclinical studies, higher absolute and relative spleen weights associated with extramedullary haematopoiesis were observed following prolonged (2 to 4 weeks) daily plerixafor subcutaneous administration in rats at doses approximately 4 fold higher than the recommended human dose.

The effect of plerixafor on spleen size in patients has not been specifically evaluated in clinical studies. Cases of splenic enlargement and/or rupture have been reported following the administration of Plerixadal^® in conjunction with growth factor G-CSF. Individuals receiving Plerixadal^® in conjunction with G-CSF who report left upper abdominal pain and/or scapular or shoulder pain should be evaluated for splenic integrity.

Sodium

Plerixadal^® contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’. (smpc)

Adult

The recommended daily dose of plerixafor by subcutaneous injection (SC) is:

• 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing ≤ 83 kg.
• 0.24 mg/kg of body weight for patients weighing > 83 kg.

Paediatric (1 to less than 18 years)

The recommended daily dose of plerixafor by subcutaneous injection (SC) is:

• 0.24 mg/kg of body weight.

Each vial of plerixafor is filled to deliver 1.2 ml of 20 mg/ml plerixafor aqueous solution for injection containing 24 mg of plerixafor.

Plerixafor has to be drawn up into a syringe size type which should be selected according to the weight of the patient.

For low weight patients, up to 45 kg of body weight, 1 ml syringes for use in infant patients can be used. This type of syringe has major graduations for 0.1 ml and minor graduations for 0.01 ml and therefore is suitable to administer plerixafor, at a dose of 240 µg/kg, to paediatric patients of at least9 kg body weight.

For patients of more than 45 kg, a1 ml or 2 ml syringe with graduations that allow a volume to 0.1 ml to be measured can be used.

It should be administered by subcutaneous injection 6 to 11 hours prior to initiation of each apheresis following 4-day pre-treatment with G-CSF. In clinical trials, Plerixadal^® has been commonly used for 2 to 4 (and up to 7) consecutive days.

The weight used to calculate the dose of plerixafor should be obtained within 1 week before the first dose of plerixafor. In clinical studies, the dose of plerixafor has been calculated based on body weight in patients up to 175% of ideal body weight. Plerixafor dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated. Ideal body weight can be determined using the following equations:

Based on increasing exposure with increasing body weight, the plerixafor dose should not exceed 40 mg/day.

Method of administration

Plerixadal^® is for subcutaneous injection. Each vial is intended for single use only.

Vials should be inspected visually prior to administration and not used if there is particulate matter or discolouration. Since Plerixadal^® is supplied as a sterile, preservative-free formulation, aseptic technique should be followed when transferring the contents of the vial to a suitable syringe for subcutaneous administration.

Adverse reactions reported with filgrastim combination therapy.

• >10%:

Central nervous system: Fatigue (27%), headache (22%), dizziness (11%)

Gastrointestinal: Diarrhea (37%), nausea (34%)

Local: Injection site reaction (34%, including edema, erythema, hematoma, hemorrhage, induration, inflammation, irritation, pain, paresthesia, pruritus, skin rash, urticaria)

Neuromuscular & skeletal: Arthralgia (13%)

• 1% to 10%:

Central nervous system: Insomnia (7%), malaise (<5%)

Dermatologic: Erythema (<5%), hyperhidrosis (<5%)

Gastrointestinal: Vomiting (10%), flatulence (7%), abdominal distension (<5%), abdominal distress (<5%), abdominal pain (<5%), constipation (<5%), dyspepsia (<5%), oral hypoesthesia (<5%), xerostomia (<5%)

Hematologic & oncologic: Hyperleukocytosis (7%)

Neuromuscular & skeletal: Musculoskeletal pain (<5%)

• <1%, postmarketing, and/or case reports: Abnormal dreams, anaphylaxis, diaphoresis, dyspnea, hypersensitivity reaction, hypoxia, leukocytosis, nightmares, orthostatic hypotension, periorbital swelling, syncope, thrombocytopenia

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Please report any adverse drug reactions via contacting Cedal Nano. ⁽¹⁾

OVERDOSAGE:

No case of overdose has been reported. Based on limited data at doses above the recommended dose and up to 0.48 mg/kg the frequency of gastrointestinal disorders, vasovagal reactions, orthostatic hypotension, and/or syncope may be higher.

No interaction studies have been performed. In vitro tests showed that plerixafor was not metabolised by P450 CYP enzymes, did not inhibit or induce P450 CYP enzymes. Plerixafor did not act as a substrate or inhibitor of P-glycoprotein in an in vitro study.

In clinical studies of patients with non-Hodgkin’s lymphoma, the addition of rituximab to a mobilisation regimen of plerixafor and G-CSF did not impact patient safety or CD34+ cell yield

• Pregnancy

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. Plerixadal® should not be used during pregnancy unless the clinical condition of the woman requires treatment with plerixafor.

• Breastfeeding

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 Plerixadal®.

Plerixafor is not recommended for use in the pediatric age group until further data become available. (smpc)

• Fertility

The effects of plerixafor on male and female fertility are not known. Women of childbearing potential have to use effective contraception during treatment.

List of excipients

Sodium chloride, Hydrochloric acid, concentrated (pH adjustment), Sodium hydroxide (pH adjustment), Water for injections

How Supplied

Store below 30° C. Keep vial in outer carton in order to protect from light.

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products

Shelf life

After opening

From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user

Special precautions for disposal and other handling

– This medicinal product does not require any special storage conditions.

– Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.