Oprelvekin (Neumega)

Oprelvekin is recombinant interleukin eleven (IL-11),[1] a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. 

 It is marketed under the trade name Neumega.

Administration s.c. injection

Bioavailability >80% by s.c. application.

Metabolism mainly renal

Elimination half-life 6.9 ± 1.7h

Chemical, pharmacological and marketing data

IL-11 is a member of a family of human growth factors and is being produced in the bone marrow of healthy adults.

Oprelvekin is produced in Escherichia coli (E. coli) by recombinant DNA technology. 

The protein has a molecular mass of approximately 19,000 g/mol, and is non-glycosylated. 

The polypeptide is 177 amino acids in length, while the natural IL-11 has 178.

Its  primary hematopoietic activity is stimulation of megakaryocytopoiesis and thrombopoiesis.

Indicated for prevention of severe thrombocytopenia following chemotherapy induced myelosuppression in adult patients with nonmyeloid malignancies.

Not indicted after myeloablative chemotherapy.

Adverse reactions include allergic or hypersensitivity reactions and anaphylaxis.

Can cause fluid retention with peripheral edema, dyspnea, pulmonary edema, capillary leak syndrome, anemia, atrial arrhythmias, and exacerbation of pericardial and pleural effusions.

Used with caution with congestive heart failure, in patients with history of congestive risk in those with risk of its development.

Less common adverse reactions include conjunctival redness, tachycardia, papilledema and moderate fluid retention.

Dose adjustments necessary for patients with renal impairment.

Side effects usually reversible within several days of stopping therapy.

In a study in which a single 50 µg/kg subcutaneous dose was administered to eighteen healthy men, the peak serum concentration (Cmax) of 17.4 ± 5.4 ng/mL was reached at 3.2 ± 2.4 h (Tmax) following dosing. 

The terminal half-life was 6.9 ± 1.7 h. 

Its absolute bioavailability is >80%. 

It does did not accumulate and clearance is not altered following multiple doses. 

In humans treated with Oprelvekin on a daily base a twofold increase in fibrinogen levels and von-Willebrand factor occurs.

Such increases in coagulation factors may contribute to the development of stroke but a precise association cannot be made at this stage.

It reduces  thrombocytopenia in oncologic patients treated with myelosuppressant chemotherapeutic drugs as measured by significantly decreased need of platelet transfusions.

It is  is indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia. 

Patients with severe or decompensated heart failure should not be treated with  Oprelvekin, as it may cause excessive fluid retention with edema and cardiac decompensation. 

Patients with compensated heart disease should be treated with caution.

It is not indicated following myeloablative chemotherapy due to increased likelihood of severe side-effects and in pediatric patients.

It is excreted renally, and no differences of pharmakinetic parameters and clinical differences have been seen in mild to moderate impairment. 

Severe renal impairment has led to an increased number of patients with reduced hemoglobin due to dilutional anemia. 

There is no sufficient human data available, so  pregnant women should only be treated, if the benefit to the mother outweighs the potential risk to the unborn.

No human data is available if the drug is distributed into human milk. 

Allergic reaction to the drug may be  very serious. 

Symptoms have been edema of the face and tongue, or larynx; shortness of breath; wheezing; chest pain; hypotension, shock, dysarthria; loss of consciousness, rash, urticaria, flushing, and fever.

It can cause fluid retention, ranging from peripheral edema in approximately 40% of patients, to dyspnea and full developed lung edema with or without cardiac decompensation.

Fluid retention lead to dilutional anemia in 10 to 15% of patients.

Hypokalemia may also occur.

Fluid retention may lead to arrhythmias (atrial flutter and atrial fibrillation) as well as cardiac arrest, and stroke.

Papilledema is observed in 2% of patients and may lead to disturbed visual acuity and even temporary or permanent blindness.

Isolated cases of severe ventricular arrhythmias and renal failure have been reported.

Injection site reactions of dermatitis, pain, and discoloration are reported but are usually mild.

The dosage in patients without severe renal impairment is 50 µg/kg subcutaneously once a day either abdominal, in thigh, or hip.

Patients with severe renal impairment should receive only 25 µg/kg daily.

The first dose should be given 6 to 24 hours after completion of chemotherapy. 

Dosing should be continued until platelet counts reach at least 50,000 cells. 

Usually, one course of treatment encompasses 10 to 21 days.

The drug should be discontinued at least 2 days before starting the next chemotherapy cycle.

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