Rpo
Rpo Uses, Dosage, Side Effects, Food Interaction and all others data.
Rpo regulates erythropoiesis by stimulating the differentiation and proliferation of erythroid precursors, stimulating the release of reticulocytes into the circulation, and synthesis of cellular haemoglobin. Recombinant human erythropoietin is available as epoetin alfa and epoetin beta which are used in the management of anaemias associated with CRF, cancer chemotherapy and anti-AIDS drug zidovudine.
Rpo and epoetin alfa are involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass. It is reported to increase the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks . Depending on the dose administered, the rate of hemoglobin increase may vary. In patients receiving hemodialysis, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly .
Epoetin alfa serves to restore erythropoietin deficiency in pathological and other clinical conditions where normal production of erythropoietin is impaired or compromised. In anemic patients with chronic renal failure (CRF), administration with epoetin alfa stimulated erythropoiesis by increasing the reticulocyte count within 10 days, followed by increases in the red cell count, hemoglobin, and hematocrit, usually within 2 to 6 weeks . Epoetin alfa was shown to be effective in increasing hematocrit in zidovudine-treated HIV-infected patients and anemic cancer patients undergoing chemotherapy .
| Trade Name | Rpo |
| Generic | Erythropoietin |
| Erythropoietin Other Names | E.P.O., Epoetin alfa, Epoetin alfa rDNA, Epoetin alfa-epbx, Epoetin alfa, recombinant, Epoetin beta, Epoetin beta rDNA, Epoetin epsilon, Epoetin gamma, Epoetin gamma rDNA, Epoetin kappa, Epoetin omega, Epoetin theta, Epoetin zeta, Epoetina alfa, Epoetina beta, Epoetina dseta, Epoetina zeta, Epoétine zêta, Epoetinum zeta, Erythropoiesis stimulating factor, Erythropoietin (human, recombinant), Erythropoietin (recombinant human), ESF, SH-polypeptide-72 |
| Type | Pree Filled Syringe Of Solution For Injection, Injection, Pre Filled Syringe Injection |
| Formula | C815H1317N233O241S5 |
| Weight | 18396.1 Da |
| Protein binding | No information of serum protein binding available. |
| Groups | Approved |
| Therapeutic Class | Drugs for Haemolytic Hypoplastic & Renal Anemia |
| Manufacturer | Rpg Life Sciences Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Anaemia in zidovudine-treated HIV-infected patients, Anaemia of chronic renal failure, Anaemia of prematurity, Anaemia related to non-myeloid malignant disease chemotherapy, To reduce the need for allogenic blood tranfusion.
Rpo is also used to associated treatment for these conditions: Anemia, Anemia caused by Zidovudine, Reduction of allogeneic RBC transfusions in patients undergoing elective, noncardiac, nonvascular surgery
How Rpo works
Rpo or exogenous epoetin alfa binds to the erythropoietin receptor (EPO-R) and activates intracellular signal transduction pathways . The affinity (Kd) of EPO for its receptor on human cells is ∼100 to 200 pM . Upon binding to EPO-R on the surface of erythroid progenitor cells, a conformational change is induced which brings EPO-R-associated Janus family tyrosine protein kinase 2 (JAK2) molecules into close proximity. JAK2 molecules are subsequently activated via phosphorylation, then phosphorylate tyrosine residues in the cytoplasmic domain of the EPO-R that serve as docking sites for Src homology 2-domain-containing intracellular signaling proteins . The signalling proteins include STAT5 that once phosphorylated by JAK2, dissociates from the EPO-R, dimerizes, and translocates to the nucleus where they serve as transcription factors to activate target genes involved in cell division or differentiation, including the apoptosis inhibitor Bcl-x . The inhibition of apoptosis by the EPO-activated JAK2/STAT5/Bcl-x pathway is critical in erythroid differentiation. Via JAK2-mediated tyrosine phosphorylation, erythropoietin and epoetin alfa also activates other intracellular proteins involved in erythroid cell proliferation and survival, such as Shc , phosphatidylinositol 3-kinase (PI3K), and phospholipase C-γ1 .
Dosage
Rpo dosage
Increase yield of autologous blood As epoetin alfa or zeta: 600 IU/kg twice wkly for 3 wk before surgery.Anaemia of chronic renal failure As epoetin alfa:
- Predialysis and haemodialysis: Initial: 50 IU/kg 3 times/wk;
- Peritoneal dialysis: 50 IU/kg twice wkly.
Anaemia in zidovudine-treated HIV-infected patients As epoetin alfa: Initial: 100 IU/kg 3 times/wk for 8 wk. Max: 300 IU/kg 3 times/wk.
Anaemia related to non-myeloid malignant disease chemotherapy As epoetin alfa or zeta: Initial: 150 IU/kg 3 times/wk, up to 300 IU/kg 3 times/wk.
Anaemia of chronic renal failure:
- Child: As epoetin alfa: Initially, 50 IU/kg 3 times wkly. May increase dose at 4 wkly intervals in increments of 25 IU/kg 3 times wkly until a target haemoglobin concentration of 9.5-11 g/100 mL is reached. Usual maintenance dose: 30 kg: 90-300 IU/kg/wk.
Side Effects
Hypertension, myalgia, arthralgia, flu-like syndrome, rashes and urticaria. Potentially Fatal: Hypertensive crisis with encephalopathy-like symptoms e.g. headache, confusion, generalised seizures. Thrombosis.
Toxicity
Overdose from epoetin alfa include signs and symptoms associated with an excessive and/or rapid increase in hemoglobin concentration, including cardiovascular events. Patients with suspected or known overdose should be monitored closely for cardiovascular events and hematologic abnormalities. Polycythemia should be managed acutely with phlebotomy, as clinically indicated. Following resolution of the overdose, reintroduction of epoetin alfa therapy should be accompanied by close monitoring for evidence of rapid increases in hemoglobin concentration (>1 gm/dL per 14 days). In patients with an excessive hematopoietic response, reduce the dose in accordance with the recommendations described in the drug label .
Precaution
Chronic renal failure, ischaemic heart diseases, hypertension, pregnancy, seizures, liver dysfunction, lactation.
Interaction
Haematinics enhance efficiency. Increased dose of heparin in patients undergoing dialysis.
Food Interaction
- Administer iron supplement. When initiating an erythropoiesis-stimulating agent, evaluate iron stores and start iron supplementation if indicated. Most patients with chronic kidney disease require iron supplementation while taking an erythropoiesis-stimulating agent.
Volume of Distribution
In healthy volunteers, the volume of distribution of intravenous epoetin alfa was generally similar to the plasma volume (range of 40–63.80 mL/kg), indicating limited extravascular distribution .
Elimination Route
The time to reach peak concentration is slower via the subcutaneous route than the intravenous route which ranges from 20 to 25 hours, and the peak is always well below the peak achieved using the intravenous route (5–10% of those seen with IV administration) . The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenously administered product and is approximately 20-40% .
Adult and paediatric patients with CRF: Following subcutaneous administration, the peak plasma levels are achieved within 5 to 24 hours .
Cancer patients receiving cyclic chemotherapy: The average time to reach peak plasma concentration was approximately 13.3 ± 12.4 hours after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing. The Cmax is expected be 3- to 7- fold higher and the Tmax is expected to be 2- to 3-fold longer in patients receiving a 40,000 Units SC weekly dosing regimen .
Half Life
Healthy volunteers: The half life is approximately 4 hours in healthy volunteers receiving an intravenous injection . A half-life of approximately 6 hours has been reported in children .
Adult and paediatric patients with CRF: The elimination half life following intravenous administration ranges from 4 to 13 hours, which is about 20% longer in CRF patients than that in healthy subjects. The half life is reported to be similar between adult patients receiving or not receiving dialysis .
Cancer patients receiving cyclic chemotherapy: Following subcutaneous administration, the average half life is 40 hours with range of 16 to 67 hours .
Clearance
*Healthy volunteers: * In male volunteers receiving intravenous epoetin alfa, the total body clearance was approximately 8.12 ± 1.00 mL/h/kg .
Cancer patients receiving cyclic chemotherapy: The average clearance was approximately 20.2 ± 15.9 mL/h/kg after 150 Units/kg three times per week (TIW) subcutaneous (SC) dosing . The patients receiving a 40,000 Units SC weekly dosing regimen display a lower clearance (9.2 ± 4.7 mL/h/kg) .
Elimination Route
Rpo and epoetin alfa are cleared via uptake and degradation via the EPO-R-expressing cells, and may also involve other cellular pathways in the interstitium, probably via cells in the reticuloendothelial scavenging pathway or lymphatic system . Only a small amount of unchanged epoetin alfa is found in the urine .
Pregnancy & Breastfeeding use
Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Contraindication
Uncontrolled hypertension, hypersensitivity to mammalian cell products and human albumin.
Storage Condition
Refrigerate at 2-8° C. Do not freeze.
Innovators Monograph
You find simplified version here Rpo
FAQ
What is Rpo used for?
Rpo is produced by the kidney and used to make red blood cells. Rpo-stimulating agents are used often for people with long-term kidney disease and anemia.
How safe is Rpo?
Rpo is generally considered safe for most people to use short term. The safety of long-term use hasn't been determined. Keep in mind supplements aren't monitored for quality by the Food and Drug Administration.
How does Rpo work?
Rpo acts on red blood cells to protect them against destruction.
What are the common side effects of Rpo?
Common side effects of Rpo are include:
- Allergic reaction. Rarely, some people have an allergic reaction to erythropoietin. ...
- Feeling sick or being sick. You may feel sick during treatment with erythropoietin. ...
- Diarrhoea
- Blood clot risk
- Headaches
- High blood pressure
- Muscle, joint or bone pain
- Flu-like symptoms.
Is Rpo safe during pregnancy?
Rpo is a safe therapy that can be used in pregnancy.
Is Rpo safe during breastfeeding?
In small studies,Rpo administration decreased serum prolactin in patients with amyotrophic lateral sclerosis, but had no effect in normal subjects or in patients with renal failure undergoing chronic ambulatory peritoneal dialysis. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
When should Rpo be given?
Rpo are usually given to patients who have chronic kidney disease or end-stage renal (kidney) disease. These patients usually have lower hemoglobin levels because they can't produce enough Rpo. Rpo are also prescribed for patients who have cancer.
How do Rpo take Rpo?
It is usually given into the thigh or tummy. A nurse can teach you, or a person caring for you, how to inject it. If you or a carer cannot give the injections, a district or practice nurse may do it for you.
How long does Rpo take Rpo to work?
It will take time for Rpo medication to work in your body. Most people take 1 to 2 months to feel better.
How often is Rpo given?
The starting dose is 50 to 100 units per kilogram (kg) injected into a vein or under the skin three times a week.
How long does Rpo stay in my system?
Rpo is undetectable in urine after 3–4 days of injection.
How much Rpo can I take daily?
The recommended Rpo regimens are: 300 Units/kg per day subcutaneously for 15 days total: administered daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery. 600 Units/kg subcutaneously in 4 doses administered 21, 14, and 7 days before surgery and on the day of surgery.
Who should not take Rpo?
You should not use this medication if you are allergic to Rpo, or if: you have untreated ,uncontrolled high blood pressure; you have had pure red cell aplasia (PRCA, a type of anemia) after using darbepoetin alfa or epoetin alfa; you use an epoetin alfa multi-dose vial and you are pregnant or breastfeeding.
When can I stop taking Rpo?
Treatment with epoetin alfa injection products should be stopped when your course of chemotherapy ends.
What happens if I overdose?
Excess Rpo results from chronic exposure to low oxygen levels or from rare tumours that produce high levels of Rpo. It causes a condition known as polycythaemia which means high red blood cell count.
What happens if I miss a dose?
Call your doctor for instructions if you miss a dose of Rpo.
Can Rpo affects my heart ?
Rpo may have a direct positive effect on the heart and brain unrelated to correction of the anemia by reducing cell apoptosis and by increasing neovascularization, both of which could prevent tissue damage.
Can Rpo affect my kidneys?
When you have kidney disease, your kidneys cannot make enough Rpo. Low Rpo levels cause your red blood cell count to drop and anemia to develop. Most people with kidney disease will develop anemia.
Does Rpo affect liver?
Rpo is produced in the liver during fetal life, but the main production shifts to the kidney after birth. The liver maintains a production capacity of up to 10% of the total Rpo synthesis in healthy controls, but can be up-regulated to 90-100%.
How does kidney make Rpo?
Rpo is a hormone that is produced predominantly by specialised cells called interstitial cells in the kidney.
How often can Rpo be given?
This Rpo is given as an injection under the skin or into a vein as directed by your doctor, usually 1 to 3 times a week.
