Granocyte34 MIU/vial

Granocyte is a recombinant human granulocyte colony-stimulating factor (G-CSF) used to support neutrophil recovery in specific, well-defined clinical settings. It is a biologic growth factor, not an antibiotic, and does not treat infection directly.

Established, guideline-supported uses

• Chemotherapy-induced neutropenia: reduction of the duration of neutropenia and its complications (including febrile neutropenia) in patients receiving established cytotoxic chemotherapy for malignancy (excluding chronic myeloid leukaemia and myelodysplastic syndromes).
• Bone marrow transplantation: reduction of the duration of neutropenia and associated clinical sequelae in patients undergoing myeloablative therapy followed by bone marrow transplantation and considered to be at increased risk of prolonged severe neutropenia.
• Peripheral blood progenitor cell (PBPC) mobilisation: mobilisation of PBPCs into the peripheral circulation, alone or following myelosuppressive chemotherapy, to accelerate haematopoietic recovery after autologous stem cell transplantation.
• Healthy donor PBPC mobilisation: mobilisation of PBPCs in healthy allogeneic donors prior to collection, to enable subsequent allogeneic stem cell transplantation.

Granocyte is used as directed by a haematologist or oncologist as part of a broader chemotherapy or transplant protocol; it is not a standalone treatment for cancer or infection.

Each vial contains Lenograstim (recombinant human glycosylated granulocyte colony-stimulating factor, produced by genetically engineered Chinese hamster ovary [CHO] cells) as a sterile, lyophilised powder, supplied together with a solvent (water for injections) for reconstitution. Common strengths contain approximately 13.4 million IU (about 105 micrograms) or 33.6 million IU (about 263 micrograms) of Lenograstim per vial; strengths and pack sizes vary by manufacturer.

Granocyte is a glycosylated recombinant form of human granulocyte colony-stimulating factor (G-CSF), a naturally occurring cytokine that regulates the production, maturation, and function of neutrophils. Unlike non-glycosylated G-CSF produced in bacterial systems, Granocyte is manufactured using Chinese hamster ovary (CHO) mammalian cell culture technology, giving it a glycosylation pattern closer to the endogenous human protein.

Granocyte is supplied as a lyophilised powder for reconstitution and administered by subcutaneous injection or intravenous infusion under medical supervision, typically in hospital or specialist oncology/haematology settings.

Colony-stimulating factor; recombinant human granulocyte colony-stimulating factor (G-CSF). Granocyte is a biologic haematopoietic growth factor and is not classified as an antibiotic, antineoplastic, or immunosuppressant.

Lenograstim binds to and activates the G-CSF receptor on committed neutrophil precursor cells and mature neutrophils, stimulating their proliferation, differentiation, and release from the bone marrow into the peripheral circulation. It also enhances the phagocytic and antibody-dependent killing functions of mature neutrophils.

Pharmacokinetics

• Absorption: after subcutaneous injection, peak serum concentrations are reached within a few hours; bioavailability is high.
• Distribution: distributes mainly within the vascular compartment and bone marrow.
• Elimination: cleared through receptor-mediated uptake by neutrophils (which increases as neutrophil counts rise) and, to a lesser extent, renal clearance; the terminal half-life is approximately 3 to 4 hours.
• Effect onset: a rise in neutrophil count is typically observed within 1 to 2 days of starting treatment, with the leukocyte count returning towards baseline within a few days of stopping.

Granocyte is administered only under medical or specialist nursing supervision, as a subcutaneous injection or, for some indications, a slow intravenous infusion over approximately 30 minutes. It must be reconstituted immediately before use (see Reconstitution) unless supplied as a ready-to-use solution.

• Do not administer in the period from 24 hours before until 24 hours after a dose of cytotoxic chemotherapy or radiotherapy.
• Rotate subcutaneous injection sites (e.g., abdomen, thigh, upper arm) to reduce local irritation.
• Do not shake the vial or reconstituted solution vigorously; gently swirl only.
• Inspect the solution visually for particulate matter or discolouration before injecting; discard if either is present.
• Self-injection by patients or caregivers should only occur after proper training by a healthcare professional, where locally permitted.

Granocyte should not be given in the period from 24 hours before until 24 hours after cytotoxic chemotherapy or radiotherapy, because rapidly dividing myeloid cells stimulated by Granocyte may be particularly sensitive to these treatments, increasing the risk of toxicity.

• Cytotoxic chemotherapy/radiotherapy: avoid concurrent administration within the 24-hour windows noted above (see also Contraindications).
• Lithium: lithium may potentiate the neutrophil-releasing effect of Granocyte; no dose adjustment is established, but this combination has not been extensively studied and should be used with awareness of potential additive leukocytosis.
• Other haematopoietic growth factors or cytokines: concurrent use with other colony-stimulating factors has not been formally studied and is not recommended outside clinical protocols.

No clinically significant interactions with common non-chemotherapy medicines have been established, but any new medicine should be reviewed by the treating physician.

Adverse effects of Granocyte range from common, generally mild and manageable reactions to rare but serious events that require prompt medical attention.

Bone pain is usually managed with standard analgesics and does not normally require stopping treatment. Patients should seek urgent medical attention for left upper abdominal or shoulder-tip pain (possible splenic rupture), breathing difficulty, cough, or fever (possible ARDS or capillary leak syndrome), or signs of a severe allergic reaction.

Pregnancy: there are limited human data on the use of Granocyte during pregnancy. Animal reproduction studies have shown adverse effects at high doses. Granocyte should be used during pregnancy only if clearly needed and the potential benefit to the mother is judged to justify the potential risk to the fetus; use only under specialist medical supervision, and always consult a physician before use in pregnancy.

Breastfeeding: it is not known whether Granocyte passes into human breast milk. As a precaution, breastfeeding should generally be discontinued during treatment with Granocyte unless a physician determines the benefit outweighs the potential risk to the infant.

Granocyte should be used only under the supervision of a physician experienced in oncology or haematology, with regular monitoring of full blood counts.

• Malignant cell growth: Granocyte has growth-factor activity and could theoretically stimulate the growth of any malignant cell type, including myeloid malignancies; safety in myelodysplastic syndrome or secondary acute myeloid leukaemia has not been established.
• Leukocytosis monitoring: white blood cell counts should be monitored regularly; treatment should generally be discontinued if the count rises excessively above the expected range for the indication, per the treating physician's protocol.
• Splenic effects: splenomegaly is common and usually asymptomatic; very rare cases of splenic rupture have been reported. Seek urgent medical review for left upper abdominal or left shoulder-tip pain.
• Pulmonary adverse effects: cough, fever, and breathlessness may be early signs of acute respiratory distress syndrome (ARDS); Granocyte should be stopped immediately and medical care sought if these occur.
• Capillary leak syndrome: characterised by swelling, low blood pressure, and low blood albumin; requires immediate medical attention and discontinuation of Granocyte.
• Sickle cell disease or trait: Granocyte has been associated with sickle cell crises, in some cases fatal; use with particular caution and close monitoring in these patients.
• Thromboembolism: use with caution in patients with pre-existing risk factors for blood clots.
• Aortitis: rare reports of inflammation of the aorta presenting as fever, abdominal pain, or elevated inflammatory markers; consider this diagnosis if such symptoms occur.
• Healthy PBPC donors: Granocyte is not generally recommended for donors over 60 years of age; donors should be monitored for at least several years given limited long-term safety data in this population.

Clinical experience with Granocyte overdose is limited. Reported experience at doses higher than recommended has generally produced an exaggerated but reversible increase in white blood cell (neutrophil) count and musculoskeletal symptoms, without other serious toxic effects being clearly established.

If an overdose is suspected, stop Granocyte immediately and seek urgent medical attention or contact emergency services/a poison control centre without delay. Management is supportive, typically involving close monitoring of the complete blood count; no specific antidote exists. White blood cell counts generally begin to fall within 1–2 days of stopping treatment and normalise within about a week. Do not attempt to manage a suspected overdose at home.

Store Granocyte at or below 30°C. Do not freeze. Keep the vial in the outer carton to protect from light, and keep out of reach of children. Granocyte must be reconstituted immediately before use unless supplied as a ready-to-use solution; once reconstituted or opened, use immediately. If immediate use is not possible, the reconstituted solution may generally be stored for up to 24 hours at 2°C–8°C (refrigerated) and protected from light — always confirm the specific product's storage instructions on the pack leaflet.

• Pediatric patients: Granocyte may be used in children over 2 years of age at the same body-surface-area-based dose as adults; safety and efficacy in children under 2 years have not been established.
• Elderly: clinical trial data in elderly patients are limited; no specific dose adjustment is established, but standard monitoring applies. Use in healthy PBPC donors over 60 years of age is generally not recommended.
• Renal or hepatic impairment: Granocyte has not been specifically studied in significant renal or hepatic impairment; use with caution and appropriate monitoring.
• Sickle cell disease or trait: use with particular caution due to the risk of sickle cell crisis (see Precautions and Warnings).
• Healthy allogeneic donors: should be carefully screened; Granocyte is avoided in donors with bleeding disorders or those on anticoagulants, and long-term follow-up is recommended.

The duration of Granocyte treatment depends on the indication and individual response, and is determined by the treating physician based on regular blood count monitoring.

• For chemotherapy-induced neutropenia and post-transplant neutropenia, treatment is typically continued daily until the expected neutrophil nadir has passed and the count has recovered to a stable, acceptable level, generally for no more than 28 days per course.
• For peripheral blood progenitor cell mobilisation, treatment is typically given for 4 to 6 consecutive days, with apheresis performed once adequate progenitor cell numbers are reached.

Granocyte should not be continued beyond the period recommended for the specific indication without physician reassessment.

Granocyte supplied as a lyophilised powder must be reconstituted with the accompanying solvent (water for injections) immediately before use. Add the solvent slowly down the side of the vial, then gently swirl to dissolve the powder completely; do not shake vigorously, as this may damage the protein and reduce effectiveness. Allow any foam to settle before withdrawing the dose. Inspect the reconstituted solution visually; it should be clear and colourless and free of visible particles — discard if cloudy, discoloured, or containing particulate matter. Presentations supplied as a ready-to-use solution or pre-filled syringe do not require reconstitution.

Colony-stimulating factors; Haematopoietic growth factors; Granulocyte colony-stimulating factors (G-CSF); Biologic/biotechnology-derived agents

Lenograstim is a recombinant analogue of endogenous human G-CSF. It binds specific cell-surface receptors on neutrophil progenitors and mature neutrophils, stimulating bone-marrow proliferation and differentiation of the neutrophil lineage and accelerating release of mature, functionally competent neutrophils into the bloodstream, thereby shortening the duration and severity of chemotherapy- or transplant-related neutropenia.

Granocyte is indicated in children over 2 years of age for the same indications as in adults (chemotherapy-induced neutropenia, post-transplant neutropenia, and PBPC mobilisation), dosed on a body-surface-area basis identical to the adult regimen. Safety and efficacy of Granocyte in infants and children under 2 years of age have not been established, and use in this age group is not recommended outside specialist clinical protocols.

Children receiving long-term treatment (for example, in the context of acute lymphoblastic leukaemia protocols) should be monitored for the rare but reported risk of secondary myelodysplastic syndrome or leukaemia, in line with the treating oncologist's protocol.