Nimotuzumab

Usage

• Nimotuzumab is prescribed for the treatment of various cancers, including head and neck cancer, glioma (a type of brain cancer), nasopharyngeal cancer, and other tumors of epithelial origin. It may also be used for pancreatic cancer and colorectal cancer in certain cases. In Cuba, it’s used in pediatric patients with recurrent brain tumors. It is often used in conjunction with radiotherapy and/or chemotherapy.
• Pharmacological Classification: Monoclonal antibody; Epidermal Growth Factor Receptor (EGFR) antagonist.
• Mechanism of Action: Nimotuzumab binds to EGFR, a protein found on the surface of many types of cells, including cancer cells. This binding inhibits the EGF pathway, which is involved in cell growth and proliferation. By blocking this pathway, Nimotuzumab can help to slow or stop the growth of cancer cells. Its lower affinity for EGFR compared to other similar antibodies makes it more selective to cells with high EGFR expression, potentially reducing side effects on healthy tissues.

Alternate Names

• h-R3
• BIOMAb EGFR
• TheraCIM
• Theraloc
• CIMAher

How It Works

• Pharmacodynamics: Nimotuzumab’s primary effect is to inhibit tumor cell growth and proliferation by binding to EGFR and blocking the EGF pathway. This leads to decreased cell signaling and reduced tumor growth.
• Pharmacokinetics:
  • Absorption: Administered intravenously, therefore 100% bioavailable in the systemic circulation.
  • Distribution: Mainly distributed in the liver, spleen, heart, kidney, and bladder, with a high uptake by the liver.
  • Metabolism: As a monoclonal antibody, metabolism is primarily through proteolytic degradation throughout the body, rather than specific organ-mediated metabolism.
  • Elimination: Primarily through proteolytic degradation, with some elimination through the urinary tract (21-34% depending on dosage). Clearance decreases with increasing dose, plateauing at doses above 200 mg. The terminal half-life ranges from 62 hours at a 50 mg dose to 304 hours at a 400 mg dose.
• Mode of Action: Nimotuzumab binds to the extracellular domain of EGFR, thereby blocking the binding of EGF and other ligands. This inhibition prevents receptor dimerization and autophosphorylation, which are essential steps in the activation of downstream signaling pathways involved in cell growth and proliferation.
• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Binds to EGFR, thereby inhibiting the receptor’s tyrosine kinase activity. It does not involve enzyme inhibition or neurotransmitter modulation.
• Elimination Pathways: Predominantly through proteolytic degradation, similar to other monoclonal antibodies, along with some urinary excretion.

Dosage

Standard Dosage

Adults:

• 200 mg weekly as a continuous intravenous infusion over 60 minutes, in combination with radiation therapy or chemotherapy. Maintenance dose may be 200 mg every two weeks. For head and neck cancers, 200 mg weekly for 6 weeks has been used concurrently with radiotherapy and/or chemotherapy.

Children:

• 150 mg/m² body surface area (BSA) weekly for 6 weeks (induction phase). Patients without disease progression at 8 weeks proceed to the consolidation phase, receiving 150 mg/m² BSA every 3 weeks until disease progression, administered as a continuous intravenous infusion over 30 minutes.

Special Cases:

• Elderly Patients: Clinical studies have included patients up to 78 years old, but no specific dosage adjustments are explicitly recommended. Use with caution due to potential age-related decline in organ function.
• Patients with Renal Impairment: No specific dosage adjustments are provided. Monitor renal function.
• Patients with Hepatic Dysfunction: No specific dosage adjustments are provided. Monitor hepatic function.
• Patients with Comorbid Conditions: Use with caution in patients with chronic diseases in decompensated phases, such as cardiac dysfunction, diabetes mellitus, or arterial hypertension.

Clinical Use Cases

• Intubation: No specific dosage guidelines for intubation are available.
• Surgical Procedures: No specific dosage guidelines for surgical procedures are available.
• Mechanical Ventilation: No specific dosage guidelines for mechanical ventilation are available.
• Intensive Care Unit (ICU) Use: No specific dosage guidelines for ICU use are available.
• Emergency Situations: No specific dosage guidelines for emergency situations are available.

Dosage Adjustments:

• No specific dosage adjustments are provided for renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms. Close monitoring of patients with these conditions is recommended.

Side Effects

Common Side Effects:

• Infusion reactions (fever, chills, nausea, vomiting)
• Skin reactions (rash, itching, dry skin)
• Fatigue
• Headache
• Nausea and vomiting
• Leukopenia (low white blood cell count)
• Elevated liver enzymes (SGPT/ALT and AST)

Rare but Serious Side Effects:

• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Allergic reactions (difficulty breathing, hives, swelling)
• Severe hypotension and urticaria
• Decreased platelets (thrombocytopenia)
• Anemia

Long-Term Effects: No specific long-term side effects are identified, but continued monitoring is recommended during prolonged use.

Adverse Drug Reactions (ADR):

• Potentially fatal allergic reactions with rapid and severe hypotension and urticaria.
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Contraindications

• Known hypersensitivity to Nimotuzumab or any of its components.
• Pregnancy and breastfeeding.

Drug Interactions

• Formal evaluations of drug interactions with other cytostatic drugs are limited.
• No significant interaction observed with gemcitabine.
• Ongoing studies with irinotecan haven’t shown untoward effects.
• Synergistic or potentiating effects with radiotherapy are noted.
• Potential for interactions with other EGFR inhibitors exists.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not established. Use is contraindicated as it may cross the placental barrier and potentially harm the fetus.
• Breastfeeding: Nimotuzumab is secreted in human milk. Breastfeeding is contraindicated while receiving treatment.

Drug Profile Summary

• Mechanism of Action: Monoclonal antibody that binds to EGFR, inhibiting cell growth and proliferation.
• Side Effects: Infusion reactions, skin reactions, fatigue, headache, nausea, vomiting, leukopenia, elevated liver enzymes. Rarely, severe allergic reactions, severe skin reactions, thrombocytopenia, anemia.
• Contraindications: Hypersensitivity, pregnancy, and lactation.
• Drug Interactions: Limited data. Potential interactions with other EGFR inhibitors or chemotherapeutic agents.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 200 mg IV weekly for 6 weeks; maintenance 200 mg every two weeks. Children: 150 mg/m² BSA IV weekly for 6 weeks; maintenance 150 mg/m² every three weeks.
• Monitoring Parameters: Complete blood count (CBC) with differential, liver function tests (LFTs), renal function (BUN, creatinine), vital signs during infusion.

Popular Combinations

• Radiotherapy: Nimotuzumab is commonly combined with radiotherapy for treating head and neck cancer and other cancers.
• Chemotherapy (cisplatin, gemcitabine, irinotecan): Concurrent use with chemotherapy is being explored and is shown to be effective and without untoward events in some cases.

Precautions

• General Precautions: Hypersensitivity reactions, pre-existing cardiovascular disease, diabetes mellitus, and other chronic conditions should be evaluated before treatment begins. Diphenhydramine pretreatment is recommended to minimize infusion reactions.
• Specific Populations:
  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Contraindicated.
  • Children & Elderly: Use with caution, monitoring for adverse events.
• Lifestyle Considerations: Limited data on interactions with alcohol or smoking are available. Consult a physician.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Nimotuzumab?

A: Adults: Typically 200 mg IV weekly for 6 weeks, then 200 mg every two weeks as maintenance. Children: 150 mg/m² BSA weekly for 6 weeks (induction), followed by 150 mg/m² every three weeks until disease progression.

Q2: What are the common side effects of Nimotuzumab?

A: Infusion reactions, skin reactions, fatigue, headache, nausea and vomiting, and leukopenia are common.

Q3: How is Nimotuzumab administered?

A: Intravenous infusion over 30-60 minutes. Premedication with diphenhydramine is recommended.

Q4: What are the contraindications to Nimotuzumab?

A: Hypersensitivity to Nimotuzumab, pregnancy, and breastfeeding are absolute contraindications.

Q5: How does Nimotuzumab work?

A: It’s a monoclonal antibody that targets EGFR, blocking the signaling pathways that promote cancer cell growth.

Q6: Can Nimotuzumab be used in children?

A: Yes, with a modified dosage regimen. It is used to treat pediatric high-grade gliomas.

Q7: What are the drug interactions of Nimotuzumab?

A: Limited information is available. Clinically significant interactions with most drugs have not been reported, though the possibility for interactions remains with chemotherapy and other EGFR inhibitors.

Q8: What monitoring parameters are recommended for patients receiving Nimotuzumab?

A: Complete blood counts, liver function tests, renal function tests and vital signs during infusion, and regular monitoring for disease progression.

Q9: What should I advise patients regarding pregnancy and breastfeeding while on Nimotuzumab?

A: Nimotuzumab is contraindicated during pregnancy and breastfeeding. Adequate contraceptive methods should be employed.