1. Oprelvekin Drugbank ID : DB00038
Protein chemical formula : C854H1411N253O235S2
Protein average weight :
Half life : 6.9 +/- 1.7 hrs

2. Description : Indication : Pharmacodynamics :
Oprelvekin, the active ingredient in Neumega® is recombinant Interleukin eleven, which is produced in Escherichia coli (E. coli) by recombinant DNA technology. The protein has a molecular mass of approximately 19,000 daltons, and is non-glycosylated. The polypeptide is 177 amino acids in length (the natural IL-11 has 178). This alteration has not resulted in measurable differences in bioactivity either in vitro or in vivo. The primary hematopoietic activity of Neumega® is stimulation of megakaryocytopoiesis and thrombopoiesis. In mice and nonhuman primate studies Neumega® has shown potent thrombopoietic activity in compromised hematopoiesis, including moderately to severely myelosuppressed animals. In these studies, Neumega® improved platelet nadirs and accelerated platelet recoveries compared to controls. In animal studies Oprelvekin also has non-hematopoetic activities. This includes the regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), the inhibition of adipogenesis, the induction of acute phase protein synthesis (e.g., fibrinogen), and inhibition of macrophageal released pro-inflammatory cytokines.
Indication :
Increases reduced platelet levels due to chemotherapy
Pharmacodynamics :
Oprelvekin 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. The primary hematopoietic activity of Oprelvekin is stimulation of megakaryocytopoiesis and thrombopoiesis. Oprelvekin has shown potent thrombopoietic activity in individuals with compromised hematopoiesis.

3. Mechanism of action : Absorption : Route of Elimination :
Oprelvekin binds to the interleukin 11 receptor which leads to a cascade of signal transduction events. IL-11 is 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.
Absorption :
Absolute bioavailability is over 80%.
Route of Elimination :
The kidney is the primary route of elimination. The amount of intact Neumega in urine was low, indicating that the molecule was metabolized before excretion.

4. Drug Interaction: Targets : Affected organisms :
Dihydrocodeine : May increase the serum levels of opioid analgesics. It is recommended to monitor therapy for the signs and symptoms of respiratory depression and enhanced sedation.
Targets :
Interleukin-11 receptor subunit alpha
Affected organisms :
Humans and other mammals .

5. Categories : Sequence :
Antineoplastic Agents and Coagulants and Thrombotic Agents
Sequence :
GPPPGPPRVSPDPRAELDSTVLLTRSLLADTRQLAAQLRDKFPADGDHNLDSLPTLAMSAGALGALQLPGVLTRLRADLLSYLRHVQWLRRAGGSSLKTLEPELGTLQARLDRLLRRLQLLMSRLALPQPPPDPPAPPLAPPSSAWGGIRAAHAILGGLHLTLDWAVRGLLLLKTRL

6. Brands : Neumega
Company : Genetics Institute Inc
Description : Interleukin eleven (IL-11) is 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. IL-11 is a member of a family of human growth factors which includes human growth hormone, granulocyte colonystimulating factor (G-CSF), and other growth factors. Oprelvekin, the active ingredient in Neumega (oprelvekin) , is produced in Escherichia coli (E. coli) by recombinant DNA technology. The protein has a molecular mass of approximately 19,000 daltons, and is non-glycosylated. The polypeptide is 177 amino acids in length and differs from the 178 amino acid length of native IL-11 only in lacking the amino-terminal proline residue. This alteration has not resulted in measurable differences in bioactivity either in vitro or in vivo.

7. Used for/Prescribed for : Prevention of severe reductions in the number of blood clotting cells (platelets) caused by some chemotherapy Formulation : Neumega (oprelvekin) is formulated in single-use vials containing 5 mg of oprelvekin (specific activity approximately 8 x 106 Units/mg) as a sterile, lyophilized powder with 23 mg Glycine, USP, 1.6 mg Dibasic Sodium Phosphate Heptahydrate, USP, and 0.55 mg Monobasic Sodium Phosphate Monohydrate, USP. When reconstituted with 1 mL of Sterile Water for Injection, USP, the resulting solution has a pH of 7.0 and a concentration of 5 mg/mL. Form : sterile, lyophilized powder Route of administration : must be injected under the skin not in the muscle.

8. Dosage : Recommended dose of Neumega (oprelvekin) in adults with severe renal impairment (creatinine clearance < 30 mL/min) is 25 µg/kg. An estimate of the patient's creatinine clearance (CLcr) in mL/min is required. Contraindication : Neumega is contraindicated in patients with a history of hypersensitivity to Neumega or any component of the product Side effects : most COMMON side effects are ; Chills; constipation; cough; diarrhea; dizziness; fever; flushing; hair loss; headache; increased cough; indigestion; inflammation or sores of the mouth or lips; joint pain; loss of appetite; mild swelling of the arms and legs; muscle pain; nausea; nervousness; pain; runny nose; shortness of breath when moving; sleeplessness; sore throat; stomach pain; vomiting; weakness. SEVERE side effects includer: Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); eye infection; eye pain; fainting; heart flutter; irregular or fast heartbeat; pain, redness, or swelling at the injection site; pounding in the chest; severe headache, dizziness, or one-sided weakness; unusual bruising; unusual or severe swelling; vision changes. Drug interaction : A total of 2 drugs (4 brand and generic names) are known to majorly interact with Neumega (oprelvekin).Ifex (ifosfamide), Ifex / Mesnex (ifosfamide / mesna), ifosfamide, ifosfamide / mesna

9. References : http://www. pfizer. com/files/products/uspi_neumega