Lenograstim

The dosage of Lenograstim is highly individualized and is usually calculated based on the patient's body surface area (BSA) or body weight.

• For Chemotherapy-Induced Neutropenia: The standard recommended dose is 150 micrograms (19.2 million IU) per square meter of body surface area per day. Alternatively, a weight-based dose of 5 micrograms (0.64 million IU) per kilogram of body weight per day is frequently used. Treatment usually begins at least 24 hours after the last dose of chemotherapy and continues until the neutrophil count has returned to a safe, stable range (usually >1.0 x 10^9/L).
• For Bone Marrow Transplantation: The dose is typically 150 micrograms per square meter per day, administered as an intravenous infusion or subcutaneous injection, starting the day after the transplant.
• For PBSC Mobilization: When used alone to mobilize stem cells, the dose is often higher, around 10 micrograms per kilogram per day for 4 to 6 days. If used after chemotherapy to mobilize cells, the standard 150 mcg/m2 dose is typically maintained.

Lenograstim is approved for use in children who are undergoing bone marrow transplantation or receiving highly toxic chemotherapy. The dosing for pediatric patients is generally the same as for adults when calculated by body surface area (150 mcg/m2/day). Clinical studies have shown that the safety profile in children is similar to that in adults, though bone pain may be reported differently by younger patients. Your pediatric oncologist will determine the exact dose based on the child's weight and the intensity of their cancer treatment.

Renal Impairment

Specific dose adjustments for patients with kidney disease are generally not required, as Lenograstim is primarily cleared through biological degradation and receptor binding rather than renal excretion. However, patients with severe renal impairment should be monitored closely for any unusual side effects.

Hepatic Impairment

There are no specific guidelines for dose reduction in patients with liver disease. Since the drug is not metabolized by the liver's P450 system, hepatic function does not significantly alter the drug's clearance. Nevertheless, clinical judgment is advised in patients with end-stage liver disease.

Elderly Patients

Clinical trials have included a sufficient number of elderly patients to demonstrate that the safety and efficacy of Lenograstim do not differ significantly from younger adults. No specific age-related dose adjustments are typically necessary, though healthcare providers will consider the patient's overall health and bone marrow reserve.

Lenograstim is administered by injection. If you are receiving this medication at home, your healthcare provider will train you or your caregiver on the proper technique for subcutaneous injection.

1. 1Preparation: Allow the vial or pre-filled syringe to reach room temperature for about 30 minutes before use. Do not shake the medication, as this can denature the protein.
2. 2Reconstitution: If using the powder form, dissolve it only with the provided solvent. Gently swirl the vial until the powder is completely dissolved. The solution should be clear and colorless.
3. 3Injection Sites: Common sites include the outer upper arms, the abdomen (avoiding the area around the navel), or the front of the thighs. Rotate the injection site with each dose to prevent skin irritation.
4. 4Storage: Store Lenograstim in the refrigerator (2°C to 8°C). Do not freeze. Keep the medication in its original carton to protect it from light.

If you miss a dose of Lenograstim, contact your healthcare provider immediately. Do not double the dose to make up for the missed one. Consistency is vital for maintaining the neutrophil count, so your doctor may advise you to take the missed dose as soon as possible or adjust your schedule.

An overdose of Lenograstim can lead to an excessively high white blood cell count (leukocytosis), which may increase the risk of vascular complications or splenic enlargement. Symptoms of overdose may include severe bone pain or abdominal pain. In the event of a suspected overdose, seek emergency medical attention. Treatment is generally supportive, and stopping the medication usually results in a rapid decline in neutrophil counts within 1 to 2 days.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the treatment without direct medical guidance from your oncology team.

The most frequently reported side effect of Lenograstim is musculoskeletal pain, particularly bone pain. This occurs because the bone marrow is rapidly expanding and producing new cells, which puts pressure on the surrounding bone structures.

• Bone Pain: This is often described as a deep ache in the lower back, hips, or sternum. It usually begins a few days before the white blood cell count rises and can often be managed with over-the-counter pain relievers like acetaminophen (paracetamol), as recommended by your doctor.
• Injection Site Reactions: Redness, swelling, or itching at the site of the subcutaneous injection is common but usually mild and temporary.
• General Malaise: Many patients report feeling tired or having a general sense of being unwell during treatment, though this is often confounded by the effects of chemotherapy.

These side effects may occur in a smaller percentage of patients:

• Headache: Mild to moderate headaches may occur shortly after administration.
• Increased Liver Enzymes: Temporary elevations in AST, ALT, or alkaline phosphatase may be seen in blood tests, usually resolving after treatment ends.
• Nausea and Vomiting: While often caused by chemotherapy, Lenograstim can occasionally contribute to gastrointestinal upset.
• Skin Rash: Some patients may develop a mild rash or hives (urticaria).

• Splenomegaly (Enlarged Spleen): Frequent or long-term use can cause the spleen to enlarge as it filters the increased number of blood cells.
• Sweet's Syndrome: A rare skin condition characterized by fever and painful, red skin lesions.
• Vascular Disorders: Rare cases of vasculitis (inflammation of the blood vessels) have been reported.
• Pulmonary Edema: Fluid accumulation in the lungs, which can cause difficulty breathing.

> Warning: Stop taking Lenograstim and call your doctor immediately if you experience any of the following symptoms:

1. 1Signs of Splenic Rupture: Severe pain in the left upper abdomen or at the tip of the left shoulder. This is a rare but life-threatening complication.
2. 2Acute Respiratory Distress Syndrome (ARDS): Symptoms include sudden shortness of breath, rapid breathing, or a persistent cough. This can occur if neutrophils accumulate in the lungs.
3. 3Severe Allergic Reactions (Anaphylaxis): Symptoms include swelling of the face, lips, or tongue, difficulty swallowing, severe dizziness, or a rapid heart rate.
4. 4Glomerulonephritis: Signs of kidney inflammation, such as blood in the urine, dark-colored urine, or puffiness in the face and ankles.
5. 5Sickle Cell Crisis: In patients with sickle cell disorders, G-CSF can trigger a severe, painful crisis.

For most patients, Lenograstim is used for short durations (7-14 days per cycle). However, for those with chronic neutropenia who use it long-term, there is a theoretical risk of developing myelodysplastic syndrome (MDS) or certain types of leukemia. While the absolute risk is low, healthcare providers monitor these patients with regular bone marrow biopsies and blood counts to ensure the benefits continue to outweigh the risks.

There are currently no FDA Black Box Warnings for Lenograstim. However, the risk of Splenic Rupture and ARDS are considered the most critical safety warnings in the product labeling across global regulatory agencies (such as the EMA). Healthcare providers are cautioned to monitor spleen size and respiratory status closely during therapy.

Report any unusual symptoms or changes in your health to your healthcare provider immediately. Keeping a diary of side effects can help your medical team manage your care more effectively.

Lenograstim is a potent biological agent that must be used with caution. It is not intended to be used to increase the dose of chemotherapy beyond established limits, as this does not necessarily improve cancer outcomes and may increase toxicity. Patients must be aware that while Lenograstim reduces the risk of infection, it does not eliminate it entirely. Strict hygiene and avoidance of crowds during the 'nadir' (the period of lowest blood counts) remain necessary.

No FDA black box warnings for Lenograstim. However, significant clinical warnings exist regarding its use in patients with certain pre-existing conditions.

• Allergic Reactions / Anaphylaxis Risk: Because Lenograstim is a protein product, there is a risk of hypersensitivity. This is particularly relevant for patients with a known allergy to G-CSF products or those with a history of sensitivity to proteins derived from Chinese Hamster Ovary (CHO) cells.
• Splenic Rupture: Cases of splenic rupture, some fatal, have been reported following the administration of G-CSF. Patients who experience left upper abdominal pain or shoulder tip pain must be evaluated immediately.
• Pulmonary Toxicity: Lenograstim can cause neutrophils to migrate to the lungs, leading to inflammation and Acute Respiratory Distress Syndrome (ARDS). If you develop a fever, cough, and difficulty breathing, notify your doctor at once.
• Capillary Leak Syndrome (CLS): This is a rare condition where fluid leaks from small blood vessels into body tissues. Symptoms include swelling or puffiness, decreased urination, and a feeling of fullness.
• Malignant Cell Growth: G-CSF receptors may be present on some types of cancer cells. There is a theoretical concern that Lenograstim could act as a growth factor for certain tumors, particularly myeloid malignancies (cancers of the bone marrow). It is generally avoided in patients with myeloid leukemia unless specifically indicated.

Patients receiving Lenograstim require frequent laboratory monitoring to ensure safety and efficacy:

• Complete Blood Count (CBC): White blood cell counts and platelet counts are usually checked two to three times per week during treatment. The goal is to avoid leukocytosis (WBC > 50,000/mm³).
• Spleen Monitoring: Physical examinations may be performed to check for an enlarged spleen.
• Urinalysis: To monitor for signs of glomerulonephritis (kidney inflammation).
• Liver Function Tests: Periodic monitoring of liver enzymes may be necessary.

Lenograstim generally does not affect the ability to drive or operate machinery. However, if you experience side effects like dizziness or severe bone pain, you should avoid these activities until you feel stable.

There are no known direct interactions between Lenograstim and alcohol. However, alcohol can dehydrate the body and strain the liver, which is already managing the effects of chemotherapy. It is best to consult your doctor regarding alcohol consumption during cancer treatment.

Lenograstim is typically stopped once the absolute neutrophil count (ANC) has surpassed a specific threshold (usually 1,000 to 2,000/mm³) for two consecutive days. There is no 'withdrawal syndrome' associated with stopping Lenograstim, but the neutrophil count will typically drop by 50% within 24 hours of discontinuation before stabilizing at the patient's natural baseline.

> Important: Discuss all your medical conditions, including any history of lung disease, kidney disease, or sickle cell anemia, with your healthcare provider before starting Lenograstim.

Cytotoxic Chemotherapy (Same-Day Administration): Lenograstim should not be administered within 24 hours before or 24 hours after a dose of cytotoxic chemotherapy.

• Mechanism: Chemotherapy targets rapidly dividing cells. Lenograstim stimulates bone marrow cells to divide rapidly. If both are given together, the chemotherapy may destroy the very cells Lenograstim is trying to produce, leading to increased bone marrow toxicity.
• Management: Always wait at least 24 hours after your last chemo dose before starting Lenograstim.

• Lithium: Lithium is known to stimulate the release of neutrophils from the bone marrow.
• Mechanism: When used with Lenograstim, there may be a synergistic (additive) effect, leading to excessively high white blood cell counts.
• Clinical Consequence: Increased risk of leukocytosis and associated vascular complications.
• Management: Frequent CBC monitoring is required if these drugs are used together.

• Fluorouracil (5-FU): While not strictly contraindicated, some studies suggest that G-CSF may worsen the drop in blood counts if given too close to 5-FU administration.
• Management: Strict adherence to the 24-hour window is essential.

• Other Cytokines: The use of Lenograstim with other growth factors, such as GM-CSF (Sargramostim) or Erythropoietin, has not been extensively studied. While they are often used sequentially, simultaneous use may alter the expected response of the bone marrow.
• Corticosteroids: Drugs like dexamethasone or prednisone can increase neutrophil counts. While often used together in cancer care, the combined effect on the white blood cell count should be monitored to avoid over-stimulation.

• Grapefruit: Unlike many drugs, Lenograstim is not metabolized by the CYP3A4 enzyme, so grapefruit juice does not interfere with its effectiveness or safety.
• General Nutrition: No specific food restrictions are required, but maintaining high protein intake and hydration supports bone marrow recovery.

• St. John's Wort: Does not have a known pharmacokinetic interaction with Lenograstim, but patients should always inform their doctor about herbal use as these can interfere with chemotherapy.
• Immune-Stimulating Herbs (Echinacea): There is a theoretical concern that herbs intended to 'boost the immune system' could interfere with the controlled stimulation provided by Lenograstim. It is generally recommended to avoid these during active treatment.

• Bone Imaging (PET/CT Scans): Lenograstim increases metabolic activity in the bone marrow. This can cause 'hot spots' on PET scans, which might be mistaken for the spread of cancer (metastasis).
• Management: Inform your radiologist if you have received Lenograstim within the last 7-10 days before a scan.
• Alkaline Phosphatase: Levels may be falsely elevated in blood tests due to increased bone marrow activity.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and vitamins.

Lenograstim must NEVER be used in the following circumstances:

1. 1Hypersensitivity to Lenograstim or CHO-derived proteins: If a patient has had a severe allergic reaction (anaphylaxis) to Lenograstim or any other G-CSF (like Filgrastim), the drug must not be used.

• Why: Re-exposure can lead to life-threatening allergic shock.

1. 1Myeloid Malignancies (Certain Types): Lenograstim should not be used in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) unless part of a specific, approved clinical protocol.

• Why: Since G-CSF is a growth factor, there is a risk that it could stimulate the growth of the cancerous myeloid cells themselves, worsening the leukemia.

1. 1Severe Congenital Neutropenia with Abnormal Cytogenetics: Patients with Kostmann syndrome who show signs of pre-leukemic changes in their bone marrow.

• Why: High risk of transformation into acute leukemia.

In these conditions, the benefits must be carefully weighed against the risks:

• Sickle Cell Disease: Lenograstim can trigger a 'sickle cell crisis' by increasing the stickiness of blood cells. Only use if absolutely necessary and under intense monitoring.
• Pre-existing Lung Disease: Patients with a history of pulmonary fibrosis or inflammation are at a higher risk for ARDS.
• Autoimmune Diseases: In rare cases, G-CSF has been reported to cause 'flares' of conditions like psoriasis or rheumatoid arthritis.

Patients who are sensitive to Filgrastim or Pegfilgrastim may also be sensitive to Lenograstim. Although Lenograstim is glycosylated and Filgrastim is not, they share significant structural homology. If you have ever had a reaction to a 'white blood cell booster' injection, you must inform your hematologist immediately.

> Important: Your healthcare provider will evaluate your complete medical history, including any prior reactions to biological drugs, before prescribing Lenograstim.

Lenograstim is generally classified as a Pregnancy Category C (or equivalent). There are limited data on the use of Lenograstim in pregnant women. Animal studies have shown some evidence of embryo-fetal toxicity at high doses, likely due to the pharmacological effects on the mother's bone marrow.

• First Trimester: Avoidance is recommended unless the risk of maternal infection is life-threatening.
• Second/Third Trimester: May be used if the potential benefit to the mother outweighs the potential risk to the fetus. It does not appear to be a potent teratogen (cause of birth defects), but its effect on the developing fetal immune system is not fully understood.

It is not known whether Lenograstim is excreted in human milk. However, since Lenograstim is a large protein molecule, it is likely to be digested in the infant's stomach if any were to pass into the milk, making absorption into the infant's bloodstream unlikely. Regardless, because of the lack of definitive data, many healthcare providers recommend suspending breastfeeding during the days the drug is being administered.

Lenograstim is safe and effective for use in children for the same indications as adults. The primary use in pediatrics is to support children undergoing intensive treatment for neuroblastoma, leukemias (in remission), or following bone marrow salvage. Long-term safety data in children with chronic neutropenia suggest a need for annual bone marrow monitoring to check for genetic changes in blood cells.

Elderly patients (over 65) are at a higher risk for infections following chemotherapy and thus often derive significant benefit from Lenograstim.

• Pharmacokinetics: No significant differences in drug clearance have been observed in the elderly.
• Risks: Older patients may have more pre-existing cardiovascular or respiratory issues, making the monitoring for ARDS or fluid retention more critical. Bone pain may also be more troublesome for patients with pre-existing osteoporosis or arthritis.

Patients with impaired kidney function (low GFR) do not typically require dose adjustments. Clinical data suggest that the drug's profile remains stable even in patients with moderate renal failure. It is not cleared by hemodialysis, so the timing of the dose relative to dialysis sessions does not need to be adjusted.

No dosage adjustment is necessary for patients with hepatic impairment. The liver does not play a primary role in the clearance of Lenograstim. However, because these patients may have baseline issues with blood clotting or splenic size, they should be monitored closely by their specialist.

> Important: Special populations require individualized medical assessment. Always ensure your medical team is aware of your pregnancy status or any chronic organ dysfunction.

Lenograstim is a recombinant human granulocyte colony-stimulating factor (rHuG-CSF). It is produced using recombinant DNA technology in a mammalian cell line (CHO cells), which allows for the glycosylation of the protein at the Thr-133 position. This glycosylation mimics the natural human protein, providing better stability and solubility compared to non-glycosylated versions.

Its molecular mechanism involves binding to the G-CSF receptor (G-CSFR) on myeloid progenitor cells. This binding causes receptor dimerization, which activates Janus Kinases (JAKs), specifically JAK2. These kinases then phosphorylate STAT proteins (Signal Transducers and Activators of Transcription), which move into the cell nucleus to turn on genes that promote cell survival, proliferation, and differentiation into mature neutrophils.

The primary pharmacodynamic effect is a dose-dependent increase in the absolute neutrophil count (ANC).

• Onset: A transient decrease in neutrophils is seen in the first 30-60 minutes (as they marginate to vessel walls), followed by a steady rise.
• Peak Effect: Maximum neutrophil counts are typically seen after 3 to 5 days of daily dosing.
• Duration: Upon stopping the drug, neutrophil counts return to baseline within 1 to 7 days (usually 48 hours).

| Parameter | Value |

|---|---|

| Bioavailability | 30% - 50% (Subcutaneous) |

| Protein Binding | Minimal (primarily receptor-bound) |

| Half-life | 3 - 6 hours |

| Tmax | 3 - 5 hours (Subcutaneous) |

| Metabolism | Endogenous proteolysis / Receptor-mediated |

| Excretion | Renal < 5%, primarily biological degradation |

• Molecular Formula: C845H1339N223O243S9 (protein component)
• Molecular Weight: Approximately 19,000 Daltons (glycosylated)
• Structure: A single-chain polypeptide consisting of 174 amino acids, with two internal disulfide bridges and one O-glycosylation site.
• Solubility: Soluble in water after reconstitution; sensitive to agitation and extreme temperatures.

Lenograstim is classified as a hematopoietic growth factor and a cytokine. It is part of the G-CSF family, which includes Filgrastim (non-glycosylated) and Pegfilgrastim (long-acting). Within the EPC (Established Pharmacologic Class) system, it is often grouped under Lymphocyte Growth Factors, though its clinical utility is specific to the granulocyte lineage.