Poexo^® (Solution) Instructions for Use

Marketing Authorization Holder

PSK Pharma, LLC (Russia)

ATC Code

L03AA13 (Pegfilgrastim)

Active Substance

Pegfilgrastim (Rec.INN registered by WHO)

Dosage Form

Poexo®

Solution for subcutaneous injection 10 mg/1 ml: syringes 0.6 ml 1 pc.

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection transparent, colorless.

Excipients: glacial acetic acid – 0.35 mg, sorbitol – 30 mg, polysorbate 20 – 0.02 mg, sodium hydroxide (for pH adjustment) – to pH 4.0, water for injections – to 0.6 ml.

0.6 ml – glass syringes with a capacity of 1 ml (1) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

Leukopoiesis stimulant

Pharmacotherapeutic Group

Immunostimulants; colony-stimulating factors

Pharmacological Action

Leukopoiesis stimulator. It is a covalent conjugate of filgrastim, recombinant human G-CSF, with one molecule of 20 kDa polyethylene glycol (PEG), with a prolonged action due to reduced renal clearance.

Similar to filgrastim, Pegfilgrastim regulates the formation and release of neutrophils from the bone marrow, significantly increases the number of neutrophils with normal or increased functional activity (chemotaxis and phagocytosis) in the peripheral blood within 24 hours and causes a slight increase in the number of monocytes and/or lymphocytes.

G-CSF stimulates endothelial cells and may accelerate the growth of myeloid cells, including malignant cells, and some non-myeloid cells in vitro.

A single administration of pegfilgrastim after each cycle of myelosuppressive cytotoxic therapy reduces the duration of neutropenia and the incidence of febrile neutropenia similarly to daily administration of filgrastim (on average, 11 daily administrations).

Pharmacokinetics

After a single subcutaneous administration, the time to reach C_max of pegfilgrastim is 16-120 hours.

The concentration of pegfilgrastim in the blood serum is maintained during the period of neutropenia following myelosuppressive chemotherapy.

The elimination of pegfilgrastim is nonlinear, dose-dependent, and saturable.

Clearance is primarily carried out by neutrophils and decreases with increasing dose of pegfilgrastim.

In accordance with the self-regulating clearance mechanism, the serum concentration of pegfilgrastim rapidly decreases with the onset of neutrophil count recovery.

Indications

Neutropenia, febrile neutropenia to reduce the duration of neutropenia and the frequency of febrile neutropenia during intensive myelosuppressive cytotoxic chemotherapy for malignant diseases.

ICD codes

Dosage Regimen

Administer subcutaneously at a single dose of 6 mg.

Inject approximately 24 hours after completion of each cycle of cytotoxic chemotherapy.

Do not administer in the period from 14 days before to 24 hours after administration of cytotoxic chemotherapy.

Use a single-dose pre-filled syringe; do not re-use or save for later administration.

Visually inspect the solution for particulate matter and discoloration prior to administration.

Discard the syringe if the solution is cloudy, discolored, or contains visible particles.

Ensure the full 0.6 ml volume from the syringe is administered to deliver the 6 mg dose.

Rotate injection sites; recommended sites include the abdomen (except the 5 cm area around the navel), front of the thighs, upper outer area of the buttocks, or upper back of the arms.

Do not inject into areas that are tender, red, bruised, scarred, or hardened.

Adverse Reactions

Musculoskeletal system: 26% – mild or moderate bone pain, which, in most cases, resolves on its own or is relieved by conventional analgesics; frequent – arthralgia, myalgia, back pain, pain in the extremities and neck.

Central nervous system: frequent – headache.

Respiratory system: cough, shortness of breath, pulmonary infiltrates, impaired respiratory function, respiratory distress syndrome.

Hematopoietic organs: splenomegaly, pain in the upper left quadrant of the abdomen; rare – vascular thrombosis; very rare – splenic rupture, leukocytosis.

Digestive system: <1% – nausea.

General disorders: frequent – chest pain (non-cardiac), fever.

Laboratory parameters: reversible, mild or moderate clinically insignificant increase in uric acid (7%), alkaline phosphatase (10%) and LDH (20%).

Allergic reactions: anaphylaxis, rash, urticaria, angioedema, shortness of breath and hypotension, at the beginning or during subsequent administration. Sometimes resumption of treatment is accompanied by a recurrence of symptoms.

Local reactions: pain at the injection site.

Contraindications

Neutropenia in chronic myeloid leukemia and myelodysplastic syndromes; acute leukemia; to increase the doses of cytotoxic chemotherapy above those established in the dosing regimens; simultaneous administration with cytotoxic chemo- and radiation therapy; pregnancy; lactation (breastfeeding); children and adolescents under 18 years of age; hypersensitivity to pegfilgrastim, filgrastim.

Use in Pregnancy and Lactation

Contraindicated during pregnancy; during lactation (breastfeeding).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

Should not be used in patients with acute leukemia receiving myelosuppressive chemotherapy (the safety and efficacy of pegfilgrastim have not been studied).

Use with caution in malignant and pre-neoplastic diseases of myeloid origin (including de novo acute myeloid leukemia and secondary); in combination with high-dose chemotherapy; in sickle cell anemia.

Use only under the supervision of an oncologist or hematologist experienced in the use of G-CSF.

The safety and efficacy of pegfilgrastim in patients receiving high-dose chemotherapy have not been studied.

Cough, fever and shortness of breath in combination with radiological infiltrative changes, deterioration of lung function and an increase in the number of neutrophils may be signs of respiratory distress syndrome in adults. In such a case, depending on the clinical situation, the drug should be discontinued and appropriate treatment prescribed.

Isolated cases of splenic rupture have been reported following the use of G-CSF, some with fatal outcomes.

The possibility of splenic rupture should be considered in patients complaining of pain in the upper left part of the abdomen or in the upper part of the left shoulder.

Monotherapy with pegfilgrastim does not preclude the development of thrombocytopenia and anemia if myelosuppressive chemotherapy is continued at the full dose. It is recommended to regularly determine the platelet count and hematocrit.

In patients with sickle cell anemia, leukocytosis is an unfavorable prognostic factor, so they require regular blood tests and consideration of the possibility of splenomegaly and vascular thrombosis.

Leukocytosis of 100×10⁹/L or more is observed in less than 1% of patients receiving filgrastim, is temporary and is usually observed 24-48 hours after drug administration in accordance with its pharmacodynamic effects. No adverse events directly related to such leukocytosis have been described.

The safety and efficacy of pegfilgrastim for the mobilization of peripheral blood stem cells in patients and healthy donors have not been adequately evaluated.

Drug Interactions

Due to the possible sensitivity of rapidly dividing myeloid cells to cytotoxic therapy, Pegfilgrastim should be administered 24 hours after the administration of cytotoxic chemotherapeutic agents.

When used concomitantly with 5-fluorouracil or other antimetabolites, potentiation of hematopoietic suppression in vivo is possible.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.