Oprelvekin (Neumega) has a similar activity as endogenous IL-11 (Interleukin 11) that stimulates platelet production. It is used in patients with thrombocytopenia caused by myeloablative chemotherapy.

Oprelvekin Uses:

• Thrombocytopenia:

  • It has been employed for the Prevention of severe thrombocytopenia and for the reduction of the need for platelet transfusions after myelosuppressive chemotherapy for non-myeloid hematological malignancy in adults who are at increase risk for thrombocytopenia.

Oprelvekin Dose in Adults

Note: Neumega use has been discontinued in the US for more than 1 year.

Oprelvekin Dose in the treatment of Thrombocytopenia:

• The dose is 50 mcg/kg once a day subcutaneously until post nadir platelet counts are more than or equal to 50,000/mm³. It should be given about 6 to 24 hours after the end of chemotherapy.
• In studies, doses were given for 10 to 21 days (not to administer for more than 21 days). The treatment should be discontinued at least 2 days before the next planned chemotherapy cycle.

Oprelvekin Dose in Children:

Note: Neumega use has been discontinued in the US for more than 1 year.

Note: The first dose should not be given until 6 to 24 hours after the end of chemotherapy. It should be noted to discontinue the drug at least 48 hours before starting the next chemotherapy cycle.

• Children:

  • The dose  25 to 50 mcg/kg one time  a day subcutaneously for 27 days was shown to be decreased toxicities and much efficacious as compared to higher doses in one study with 47 pediatric patients;
  • Dosing should continue until post nadir platelet count more than or equal to 50,000/mm

Note: The manufacturer states that, until efficacy/toxicity parameters are established, the use of oprelvekin in pediatric patients (particularly those <12 years of age) should be restricted to use in controlled clinical trials

Pregnancy Risk Factor C

• Negative events have been documented in animal reproduction studies.

Oprelvekin use during breastfeeding:

• It is not known if breastmilk contains it.
• The manufacturer suggests that you stop breastfeeding, or discontinue using the drug, due to the potential for adverse reactions in breastfeeding infants.

Dose in Kidney Disease:

For dosage adjustment purposes, renal function may be estimated using the Cockcroft-Gault formula.

• CrCl ≥30 mL/minute:

  • No dosage adjustment is necessary.

• CrCl <30 mL/minute:

  • Reduce the dose to 25 mcg/kg once daily.

Dose in Liver Disease:

No dose adjustments were provided in the manufacturer's guidelines.

Common Side Effects of Oprelvekin:

• Cardiovascular:

  • Tachycardia
  • Edema
  • Cardiomegaly
  • Vasodilation
  • Atrial Arrhythmia
  • Palpitations
  • Syncope

• Central Nervous System:

  • Headache
  • Dizziness
  • Insomnia

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Fluid Retention

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea
  • Mucositis
  • Oral Candidiasis

• Hematologic & Oncologic:

  • Febrile Neutropenia
  • Anemia

• Neuromuscular & Skeletal:

  • Severe Weakness
  • Periosteal Disease
  • Arthralgia

• Ophthalmic:

  • Conjunctival Edema
  • Conjunctival Erythema
  • Conjunctival Injection
  • Papilledema

• Respiratory:

  • Dyspnea
  • Rhinitis
  • Cough
  • Pharyngitis
  • Pleural effusion

• Miscellaneous:

  • Fever

Contraindications to Oprelvekin:

Hypersensitivity to any component of the formulation or oprelvekin

Warnings and precautions

• Anemia (dilutional):

  • Increased plasma volume may cause dilutional anemia. This can manifest as mild decreases in hemoglobin, hematocrit and red blood cell count without a decrease of red blood cell mass.
  • The effect usually appears within 3 to 5 working days. It will resolve over about a week after oprelvekin is stopped.

• Cardiovascular effects

  • There have been reports of arrhythmias, pulmonary edema and cardiac arrest.
  • Patients with a history or atrial arrhythmia should not use this medication unless the potential benefits outweigh the possible risks.
  • Stroke has been reported in patients who develop atrial fibrillation/flutter while receiving oprelvekin (patients with a history of stroke or transient ischemic attack may be at risk for atrial fibrillation/flutter).
  • Also, ventricular arrhythmia was reported to occur within 2-7 days of treatment.

• Fluid retention:

  • This may cause fluid retention that is not reversible within a few days.
  • It can also result in peripheral edema and dyspnea as well as capillary leak syndrome, capillary leak syndrome, arrhythmias, and exacerbation or worsening of preexisting pleural effusion.
  • There have been cases of serious fluid retention, sometimes fatal. 
  • Patients with heart disease, such as those with heart attack or other symptoms, patients on aggressive hydration and patients with heart problems, who have been well compensated, who receive appropriate treatment, and patients who have had heart attacks in the past, should be cautious. Fluid retention can also be caused by medical conditions.
  • Monitoring fluid and electrolyte levels is important. Preexisting fluids such as pericardial effusions and ascites should be checked. Drainage may be necessary.

• Hypersensitivity reactions: [US Boxed Warning]

  • There have been reports of anaphylaxis and allergic reactions. 
  • If a patient develops an allergic reaction or hypersensitivity, discontinue use of the medication. You may experience an allergic reaction to the first dose or subsequent doses.
  • Allergy reactions include: dyspnea, tongue/ larynx edema and wheezing.

• Papilledema:

  • Papilledema is a condition that occurs after repeated cycles. Children were more likely to experience papilledema.
  • Patients with pre-existing papilledema and CNS tumors should be cautious.
  • Opelvekin-related eye papilledema can lead to vision acuity and/or visual field defects. This could cause blurred vision or blindness.

• Renal impairment

  • Patients with kidney impairment should be cautious (oprelvekin is excreted through the kidneys).
  • In severe renal impairment, dosage adjustment may be required. Monitor fluid balance.

Monitoring Parameters:

• During therapy, electrolyte and fluid balance should be monitored.
• A full blood count at regular intervals should be monitored.
• Platelet count should be monitored during the time of expected nadir and until adequate recovery has occurred.

How to administer Oprelvekin?

• It is administered as a subcutaneous injection.
• The abdomen, thigh or hip, and outer upper arm should be used for subcutaneous administration.

Mechanism of action of Oprelvekin:

• Oprelvekin mimics IL-11's endogenous activity, which is a thrombopoietic factor. 
• It stimulates platelet formation by stimulating the proliferation of megakaryocyte progenitors, megakaryocyte maturation, and megakaryocytopoiesis.

The onset of action:

• 5 to 9 days;
• The maximum effect: 14 to 19 days

Duration of action:

• Up to 7 days after discontinuation

Bioavailability:

• Greater than 80%

Half-life elimination:

• Terminal: 6.9 ± 1.7 hours

Time to peak serum concentration:

• 3.2 ± 2.4 hours

Excretion:

• It is excreted in Urine primarily as metabolites.

International Brand Names of Oprelvekin:

• Neumega
• Jijufen
• Neumega
• Plaquemax
• Yi Xing

Oprelvekin Brand Names in Pakistan: