Neupogen is a granulocyte colony-stimulating factor that is in man-made form. The bacterium that is used in making this drug is Escherichia coli. Granulocyte colony-stimulating factor substance is produced by stimulation of the body cells. Neupogen drug has been widely used and has shown great effectiveness previously in patients suffering from cancer. It is preferred to people fighting cancer since it can stimulate the replication of the white blood cells in the body mostly referred to as the neutrophils. The benefit of the production of more blood cells among these patients is because the latter reduces their body’s’ vulnerability to infections. The major target patients among those who are at high risk of developing cancer are those with bone marrow damage which resulted from high radiation doses. Neupogen, which is also chemically known as filgrastim, is clinically approved for the patients who have marrow destruction most probably because of uncontrolled bleeding and infection (Kayser and Heribert 43).
Despite the fact that Neupogen drug is not clinically recommended for FDA purposes to treat those who have had high radiation doses, it might be authorized to be used in emergency situations. The patients who get high radiation doses will not be capable of producing new leucocytes. It will result in a reduction in the production of white blood cells in the circulation. In cancer patients, the bone marrow of the patient will gradually create new body cells even though this is a very low process. Until the counts of the white blood cells rise sufficiently, the patients suffering from this disorder are at risk of dying from infections (Kayser and Heribert 74). The drug can speed up the production rate of these white blood cells in the individuals fighting cancer hence reducing the duration that the patients are vulnerable to infections.
In as much as the effectiveness of this drug has been confirmed by several pharmacological platforms for people with high dose of radiation exposure, individuals who have reported cases of hypersensitivity to Escherichia coli-derived proteins, any filgrastim component and filgrastim itself should avoid the drug at all necessary costs. The drug is mostly safe for adults and children as well as pregnant women should take a lot of caution when taking Neupogen. It is not well established whether the Neupogen components can be excreted in the breastfeeding mother’s milk and for this reason, the lactating mothers are advised to have further discussion of this matter with their doctors.
The drug comes in two distinct forms. It can either be administered in single-use vials or pre-filled syringes. Each milliliter of clear, sterile and colorless liquid is formulated in the acetate buffer of sodium with a 5% sorbitol. In this form, the drug is availed in single use with free vials preservatives of 1 milliliter. The same procedure used in the single-use vials is used in the pre-filled syringes the only difference is that the second method entails the use of dry latex or natural rubber.
Neupogen has reported several cases of negative effects. These include spleen rupture, severe lung problem known as acute respiratory distress syndrome and serious allergic reactions. Other side effects also worth noting are sickle cell crises, capillary leak syndromes, increased blood count, and decreased the platelet count and inflammation of blood vessels. Continued use of Neupogen drug may cause the spleen of the patient to become larger in size and more dangerously lead to the rupture of the spleen leading to death. It can be manifested by the pain in the lower abdomen or the left upper stomach or the areas of one’s left shoulder (Huml 23). This drug can also cause serious reactions of allergy. The reactions may lead to rashes over the entire body. Allergic reactions also cause dizziness, wheezing, shortness of breath, fast pulse, sweating and swelling around the eyes or mouth. The use of Neupogen should be stopped immediately, or doctor’s consultation sought in case of the above-listed symptoms.
The condition of the sickle cell may progress to a more severe situation in case someone with sickle cell disorder uses this drug. Serious and in most occasions fatal crises of the sickle cell may occur in patients suffering from this disorder and at the same time under filgrastim treatment. The drug can cause leakage of fluid from the blood vessels into the tissues of the body a condition medically known as a capillary leak syndrome. The symptoms of this condition may be life threatening therefore in case one develops any syndrome suggesting such condition; emergency precautions ought to be taken. Uptake of Neupogen may also lead to bruising or unusual bleeding. It could mean the reduction in the number of platelets is making the blood clotting process futile. Finally, the use of this drug among the cancer patients may lead to reddening of the skin or the skin developing purple dots, a condition mostly referred to as cutaneous vasculitis. Most commonly, the negative effects of Neupogen revolves in the pain in the muscles and bones (Huml 56).
In pharmacodynamics, a study of the effectiveness of Neupogen was conducted among patients who had non-myeloid malignancies. The administration of Neupogen resulted into an increase of dose-dependent in circulating counts of neutrophil over the daily dose range in the experiment conducted, the observation was made when Neupogen was administered subcutaneous, intravenous and continuous subcutaneous infusion. The withdrawal of Neupogen therapy led to a decreased count of neutrophil in most cases to baseline for the days of conducting the experiment. The isolated samples of neutrophil showed normal phagocytic and chemotactic activity in vitro. The absolute count of monocyte was indicated to increase in a manner of dose-dependent in the majority of patients who received Neupogen. However, the monocyte percentage in the differential count stood at the normal range.
The absolute count of both basophils and eosinophils were not altered and remained to be within the normal range for the administration of Neupogen. There has also been a reported case of an increase in the count of lymphocytes following administration of Neupogen in patients with cancer and some normal subjects. The differentials of white blood cells obtained at the period of clinical trials have illustrated a shift towards the earlier granulocytes progenitor cells including myeloblasts and promyelocytes appearance usually during the recovery of neutrophil following the nadir induced chemotherapy. Also, there was also a reported increase in dohle bodies, increased hypersegmented neutrophils, and granulocyte granulation being observed. The changes and alterations observed during the period of pharmacodynamics were neither linked to clinical sequelae nor with any merely thought infection.
Neupogen exhibits non-linear pharmacokinetics. The clearance of the drug is dependent on the concentration of filgrastim and the count of the neutrophil. The Granulocyte colony-stimulating factor receptor-mediated clearance has a high level of saturation of Neupogen concentration and is also diminished by neutropenia. Moreover, filgrastim is cleared by the glomerular of the kidney. Subcutaneous administration of a small quantity of filgrastim produced a maximum concentration of serum within a short span of time. After administration of the drug intravenously, the result turned out an average of what was administered first and the elimination of half-life produced was nearly few hours in both cancer patients and the normal subjects. Daily intravenous doses or single parenteral doses over a period of 14 days led to comparable half-lives (Geigert 47). The obtained half-lives were identical for intravenous administration and administration done subcutaneously. Continuous daily intravenous infusions for several days produced serum of steady state concentration of filgrastim without evidence of accumulation of drugs over the investigated period. The absolute filgrastim bioavailability after subcutaneous administration was more than sixty per cent.
Pharmacologically, the colony-stimulating factors are compounds of glycoproteins acting on the hematopoietic cells. They achieve this by binding to the surface of specific cell receptors and differentiation commitment, stimulating proliferation and some activation of end cell function. Endogenous Granulocyte colony-stimulating factor is a specific colony lineage produced by fibroblasts, monocytes, and the endothelial cells.
They help in the regulation of neutrophils production in the bone marrow as well as affecting the neutrophil progenitor differentiation, proliferation and functions of the selected end cells including enhancing the phagocytic ability, the killing of antibody-dependent, priming of cellular metabolism linked with respiratory burst and the continuous expression of cell surface antigens. Granulocyte colony-stimulating factor is not species-specific and has shown minimal direct in vitro or in vivo effects on the activity or the production of hematopoietic types of cells other than the lineage of the neutrophils (Geigert 132).
Kayser, Oliver, and Heribert Warzecha. Pharmaceutical Biotechnology: Drug Discovery and Clinical Applications. Weinheim: Wiley-Blackwell, 2012. Print.
Huml, Raymond A. Pharmaceutical Competitive Intelligence for the Regulatory Affairs Professional. New York: Springer, 2012. Print.
Geigert, J. The Challenge of Cmc Regulatory Compliance for Biopharmaceuticals and Other Biologics. New York, NY: Springer, 2013. Internet resource.