Usage
- Molgramostim is prescribed to stimulate the production of white blood cells (specifically neutrophils) in patients with neutropenia, a condition characterized by low neutrophil counts. This condition can arise from chemotherapy, bone marrow transplantation, or the use of certain medications like ganciclovir. It is also being investigated for use in acute respiratory distress syndrome (ARDS) and autoimmune pulmonary alveolar proteinosis (aPAP).
- Pharmacological classification: Colony-stimulating factor (CSF), Immunomodulator.
- Mechanism of action: Molgramostim acts as a granulocyte-macrophage colony-stimulating factor (GM-CSF) analog. It binds to specific cell surface receptors, stimulating the proliferation, differentiation, and activation of myeloid progenitor cells in the bone marrow, ultimately increasing the production of neutrophils, monocytes, and macrophages.
Alternate Names
- International Nonproprietary Name (INN): Molgramostim
- Brand names: Leucomax, Macrogen (India), Leukin (US - discontinued).
How It Works
- Pharmacodynamics: Molgramostim primarily affects the hematopoietic system by promoting the growth and maturation of neutrophils, monocytes, and macrophages. It also enhances the functional activity of mature neutrophils, such as phagocytosis and cytotoxicity. It reduces the duration and severity of neutropenia and decrease the risk of infections. It may influence the maturation and differentiation of dendritic cells, possibly affecting antigen presentation.
- Pharmacokinetics: Administered subcutaneously or intravenously. Peak serum concentrations are reached within 1-4 hours. The elimination half-life is approximately 1.5-2 hours. Metabolism and elimination pathways are not fully characterized but are thought to involve degradation by proteases and elimination through kidneys.
- Mode of action: Binds to the GM-CSF receptor (a heterodimer composed of alpha and beta subunits), activating intracellular signaling pathways (JAK/STAT) that lead to gene transcription and protein synthesis, promoting cell proliferation, differentiation, and functional activation of target cells.
Dosage
Standard Dosage
Adults:
- Neutropenia related to Chemotherapy: 5-10 mcg/kg daily for 7-10 days, usually starting 24 hours after the last dose of chemotherapy. Dosage can be adjusted after five doses based on neutrophil counts. Maximum dose: 10 mcg/kg daily.
- Bone marrow transplantation: 10 mcg/kg daily by infusion over 4-6 hours, initiated the day after the procedure and continued for up to 30 days depending on neutrophil count. Alternatively, a starting dose of 5 mcg/kg/day can be administered and adjusted after the fifth dose.
- aPAP: 300 mcg inhaled once daily.
Children:
- Pediatric dosing is determined by body weight (e.g., 10-12 mcg/kg in children under 40kg) and requires careful consideration of age and clinical status.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on renal and hepatic function.
- Patients with Renal Impairment: Dose modifications required.
- Patients with Hepatic Dysfunction: Dose adjustments may be necessary.
Clinical Use Cases (dosage based on standard adult recommendations unless otherwise specified).
- Surgical procedures
- Mechanical ventilation
- Intensive care unit (ICU)
Dosage Adjustments
- Dosage adjustments may be required based on patient response and tolerance to therapy.
Side Effects
Common Side Effects
- Fever, chills, nausea, dyspnea, diarrhea, rash, injection site reaction (subcutaneous administration), vomiting, fatigue, anorexia, bone and musculoskeletal pain, asthenia, transient hypotension, non-specific chest pain, stomatitis, headache, increased sweating, abdominal pain, pruritus, dizziness, peripheral edema, paresthesia, myalgia.
Rare but Serious Side Effects
- Allergic reactions (including anaphylaxis), pleural and pericardial effusion, fluid retention, cardiac arrhythmias, pulmonary toxicity (especially with bleomycin), exacerbation of pre-existing lung disease.
Long-Term Effects
Contraindications
- Myeloid malignancies
- Hypersensitivity to molgramostim or any component of the formulation.
- Lactation
Drug Interactions
- May potentiate the pulmonary toxicity of bleomycin.
- Increased risk of myelosuppression with concomitant myelosuppressive chemotherapy. Should not be administered within 24 hours of cytotoxic chemotherapy.
- Medications that induce myeloproliferation.
Pregnancy and Breastfeeding
- Pregnancy: Safety not established; animal studies have shown adverse effects. Use only if potential benefits outweigh risks.
- Breastfeeding: Contraindicated due to potential adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: GM-CSF analog stimulating myeloid cell proliferation and differentiation.
- Side Effects: Fever, chills, nausea, rash, bone pain, fluid retention, allergic reactions, pulmonary toxicity.
- Contraindications: Myeloid malignancies, hypersensitivity, lactation.
- Drug Interactions: Bleomycin, myelosuppressive chemotherapy, medications that induce myeloproliferation.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 5-10 mcg/kg/day (adjustments may be needed).
- Monitoring Parameters: Neutrophil count, complete blood counts, pulmonary function, signs of fluid retention.
Popular Combinations (not generally recommended unless clinically indicated)
- May be used in combination therapy with certain antivirals (e.g., ganciclovir) to mitigate neutropenia.
Precautions
- General precautions: Monitor complete blood counts, assess for fluid retention, evaluate pulmonary function (especially in patients with pre-existing lung disease).
- Pregnant Women: Weigh risks and benefits carefully.
- Breastfeeding mothers: Avoid use.
- Children & Elderly: Dose adjustments based on weight, renal and hepatic function.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Molgramostim?
A: Dosage is weight-based and depends on the indication. 5-10 mcg/kg daily is common for chemotherapy-induced neutropenia, with adjustments after five doses based on neutrophil counts. For bone marrow transplantation, it can be administered as 10 mcg/kg/day or starting with 5 mcg/kg/day followed by dosage adjustments. Maximum dose is generally not to exceed 10 mcg/kg/day.
Q2: How is Molgramostim administered?
A: Subcutaneous injection or intravenous infusion. Inhaled administration for aPAP.
Q3: What are the common side effects?
A: Fever, chills, bone pain, nausea, rash, and injection site reactions.
Q4: What are the serious side effects to be aware of?
A: Allergic reactions (including anaphylaxis), fluid retention, pulmonary toxicity (especially in combination with bleomycin), and cardiac arrhythmias.
Q5: What are the contraindications for Molgramostim?
A: Known hypersensitivity, myeloid malignancies, and breastfeeding.
Q6: Can Molgramostim be used in pregnant women?
A: Not generally recommended unless the potential benefits clearly outweigh the risks. Animal studies have shown adverse effects.
Q7: How does Molgramostim interact with other medications?
A: May increase the risk of pulmonary toxicity with bleomycin. Should not be used within 24 hours of myelosuppressive chemotherapy. Avoid concomitant use with drugs that induce myeloproliferation.
Q8: How should I monitor patients receiving Molgramostim?
A: Close monitoring of complete blood counts (especially neutrophils), signs and symptoms of fluid retention, and respiratory function (particularly in patients with pre-existing lung conditions) are essential.
Q9: What is the role of Molgramostim in bone marrow transplantation?
A: Used to accelerate myeloid recovery and reduce the duration of neutropenia following bone marrow transplantation, thereby reducing the risk of infections.
