Erythropoietin is naturally secreted by the kidney in response to low blood oxygen level. This stimulates RBC production in the bone marrow to correct the hypoxic state. Recombinant human erythropoietin compound- genetic engineering technology is employed to obtain recombinant human erythropoietin which has the same amino acid sequence as erythropoietin obtained from the urine. Erythropoietin Systems Haematopoietic System Category Hamatopoietic growth factor Pharmacokinetics Erythropoietin has a molecular weight of 36,000. It is a glycoprotein hormone which is given intravenously or subcutaneously. Its plasma half life is about 6-8 hrs. It acts on the early erythroid colony forming unit of bone marrow. It induces hemoglobin formation and erythroblast maturation and releases reticulocytes in circulation. Indications It is given to increase the reticulocyte formation. It is given in anemia of chronic renal failure, those related to non- myeloid malignant disease, HIV patients with zidovudine related anemia and to increase the yield of autologous blood . Routes of Administration and Dosage For injection dose : For severe anemia in Adults: The usual dose is 50 to 100 Units per kilogram (kg) of body weight three times a week, injected IV or subcutaneously. The dose is gradually decreased by 25 Units per kg of body weight every four weeks or more until the lowest effective dose is reached. Most patients who have low iron stores require concurrent iron therapy for optimal response. Contra Indications Erythropoietin is contraindicated in uncontrolled hypertension, hypersensitivity to mammalian cell products and hypersensitivity to human albumin. Precautions Those with history of thrombosis, heart disease or hypertension may have increased chances of adverse effects. In those with sickle cell anemia Erythropoietin is not effective. The chance of seizures may be increased in those with history of Seizures. Interactions Haematinics may enhance the effect of erythropoietin. The dose of Heparin should be increased in those undergoing dialysis. *Haematinics are the chemical agents or substances which are required for normal erythropoiesis. These are—Iron (Fe), Cobalt (Co), Zinc (Zn), Vit-B12, Folic acid and Erythropoietin.
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Transcript
Erythropoietin is naturally secreted by the kidney in response to low blood oxygen level. This stimulates RBC production in the bone marrow to correct the hypoxic state.
Recombinant human erythropoietin compound- genetic engineering technology is employed to obtain recombinant human erythropoietin which has the same amino acid sequence as erythropoietin obtained from the urine.
Erythropoietin
Systems Haematopoietic System Category Hamatopoietic growth factor
Pharmacokinetics
Erythropoietin has a molecular weight of 36,000. It is a glycoprotein hormone which is given intravenously or subcutaneously. Its plasma half life is about 6-8 hrs. It acts on the early erythroid colony forming unit of bone marrow. It induces hemoglobin formation and erythroblast maturation and releases reticulocytes in circulation.
Indications
It is given to increase the reticulocyte formation. It is given in anemia of chronic renal failure, those related to non-myeloid malignant disease, HIV patients with zidovudine related anemia and to increase the yield of autologous blood .
Routes of Administration and Dosage
For injection dose : For severe anemia in Adults: The usual dose is 50 to 100 Units per kilogram (kg) of body weight three times a week, injected IV or subcutaneously. The dose is gradually decreased by 25 Units per kg of body weight every four weeks or more until the lowest effective dose is reached. Most patients who have low iron stores require concurrent iron therapy for optimal response.
Contra Indications
Erythropoietin is contraindicated in uncontrolled hypertension, hypersensitivity to mammalian cell products and hypersensitivity to human albumin.
Precautions
Those with history of thrombosis, heart disease or hypertension may have increased chances of adverse effects. In those with sickle cell anemia Erythropoietin is not effective. The chance of seizures may be increased in those with history of Seizures.
Interactions
Haematinics may enhance the effect of erythropoietin. The dose of Heparin should be increased in those undergoing dialysis.
*Haematinics are the chemical agents or substances which are required for normal erythropoiesis.
These are—Iron (Fe), Cobalt (Co), Zinc (Zn), Vit-B12, Folic acid and Erythropoietin.
epoetin alfa
Available Brands
Efotin Epogen
Epokine Eposino
Epotin Epovax
Eprex Renogen
Epokine
Manufacturer CJ Corp
Distributor B Braun
Marketer Macropharma Corp
Contents/Description Epoetin-α. Epokine also contains human serum albumin 2.5 mg/mL as stabilizer.
Indications
Treatment of Anemia associated with chronic renal failure, including patients on dialysis and not on dialysis. To elevate or maintain red blood cell level and to decrease the need for transfusions. Treatment of Anemia in Cancer Patients on Chemotherapy
MIMS Class
Haematopoietic Agents
ATC Classification
B03XA01 - erythropoietin; Belongs to the class of other antianemic preparations.
Presentation/Packing
Inj (pre-filled syringe, sterile, colorless solution) 2000 IU/0.5 mL x 1's. 4000 IU/0.4 mL x 1's. 10,000 IU/mL x 1's. *IU-International Unit
Mechanism of Action
Epoetin-α is a recombinant human erythropoietin, type a. It is a glycoprotein hormone which stimulates the division and differentiation of committed erythroid progenitors in the bone marrow. Epoetin-α frees the same biological and immunological effects as endogenous erythropoietin and contains the identical amino acid sequence of isolated neutral erythropoietin.
Dosage
Chronic Renal Failure (CRF) Patients: Initial Dose: 60 units/kg for 1-2 min 3 times a week, IV or SC for patients with CRF who are not on dialysis. The dose increase is dependent upon the initial response. The dose can be increased if necessary by 25 units/kg in a 4-week period. If hemoglobin is increased >2 g/dL at a dose of 50 units/kg, the frequency should be reduced to twice a week. To correct the anemia, the target concentration of hemoglobin is 10 g/dL (30% as hematocrit). When anemia is corrected, epoetin-α is given at a maintenance dose of 25-50 units/kg 2 or 3 times a week. The target range of hemoglobin <6 g/dL needs higher maintenance dose than those patients with pre-treatment hemoglobin >8 g/dL. And the dose may be adjusted according to the age of the patient. The unit dose of epoetin-α should not exceed 200 units/kg, and the frequency should not be more than 3 times a week. Prior to initiation of therapy or during the therapy, the patient's iron stores should be evaluated; if necessary, iron should be supplied. If patients are in aluminum intoxication or infected, delayed or diminished responses may occur. In patients with CRF not on dialysis, the maintenance dose must also be individualized according to the severity of anemia or age, however, the dose of 70-150 units/kg/week have been shown to maintain 36-38% of hematocrit for >6 months.
Overdosage The dose response of Epokine depends upon the conditions of the patient. In case of
overdosage, hypertension may occur. If polycythemia is of concern, phlebotomy may indicate the decrease of hematocrit.
Contraindications
Known hypersensitivity to Epokine or to other erythropoietin products. Uncontrolled hypertension, known hypersensitivity to mammalian cell-derived products or albumin (human).
Warnings
Epoetin-α treatment should be limited in anemic patients with CRF <10 g/dL of hemoglobin (30% as hematocrit). Epoetin-α should not be used in patients with anemia from blood loss, hematocytopenia and aluminum intoxication. Special monitoring of patient's history should be done to forecast shock or other responses. Low dosage should be allowed by IV route to determine a patient's responsiveness to the administration of epoetin-α before the initiation of therapy or resumption after withholding. During the epoetin-α therapy, hemoglobin concentration or hematocrit should be observed periodically (once a week at initial therapy, biweekly at maintenance therapy). Special caution should be taken not to result in excessive erythropoiesis (>12 g/dL of hemoglobin or 36% of hematocrit). In case of excessive erythropoiesis, withholding of the drug or appropriate treatment should be taken. Hypertension and hypertensive encephalopathy have been reported in patients treated with epoetin-α, associated with a significant increase in hematocrit. Hematocrit increase may occur in case of discontinuation of the therapy. Blood pressure in patients treated with epoetin-α should be monitored carefully, particularly in patients with a fast rise of hematocrit (>4% in any 2-week period) owing to the potential for an increased risk. Seizures have occurred in patients with CRF participating in Epokine clinical trials. In patients on dialysis, there was a high incidence of seizures during the first 90 days of therapy (occurring in approximately 2.5% of patients) as compared with later time Seizures in 1.6% of patients treated with Epokine occurred in the context of a significant increase in blood pressure and hematocrit from baseline values. However, patients treated with Epokine also had underlying CNS pathology which has been related to seizure activity. Given the potential for an increased risk of seizures during the therapy, blood pressure and the presence of premonitory neurologic symptoms should be monitored closely. Thrombotic events may occur eg, myocardial infarction, pulmonary embolism, cerebrovascular accident or ischemic attack. The patients with vascular disease should be monitored cautiously. Since hyperkalemia may occur, the importance of compliance with dietary prescriptions should be reinforced. Shunt infarct or residual blood in dialysis kit may occur, so careful monitoring of blood circulation in shunt or dialysis kit is a must. In case of iron deficiency, adequate iron supplementation is very important in order to support erythropoiesis. Epoetin-α is a growth factor that primarily stimulates red blood cell production. However, the possibility that epoetin-α can act as a growth factor for any tumor type, particularly myeloid malignancies, cannot be excluded. Use in pregnancy: The safety of Epokine in pregnant women has not been established. It should be used in pregnancy only if potential benefit justifies the risk. Use in children: Safety of Epokine in children has not been established. Use in the elderly: When Epokine is administered to geriatric patients, dosage and frequency should be controlled on the basis of the observed blood pressure, hemoglobin concentration or hematocrit.
Special Precautions
Epoetin-α should be administered with caution to the following patients: Patients with hypertension (blood pressure may rise or hypertensive encephalopathy may occur during epoetin-α therapy), known hypersensitivity to drugs or history of allergic reactions to drugs,
myocardial infarction, pulmonary infarction or cerebral embolus and cerebral bleeding or premature infant with cerebral bleeding.
Adverse Drug Reactions
Shock: As shock has been reported, full observation should be taken. If the symptoms appear, the administration should be discontinued and an appropriate treatment should be taken. Cardiovascular: Hypertension, thrombosis of lacrimal duct or A-V shunt and tachycardia have been reported rarely. Hypertensive Encephalopathy: As hypertensive encephalopathy (shows headache, conscious disorder and seizures) and cerebral hemorrhage have been reported occasionally, the drug should be administered cautiously with observation of the trends of blood pressure and hematocrit during therapy. Cerebral Embolus: As cerebral embolus has been reported, full observation should be taken. Skin: Itching, skin rash and decubitus have been reported. Liver: Elevation in AST, ALT, LDH, AL-P and total bilirubin may occur occasionally. Blood: Leukocytosis, eosinophilia have been reported and granulocytopenia may occur in premature infants. Increased serum kalium, BUN, creatinine and uric acid have been reported. GI: Nausea, vomiting, anorexia, diarrhea and abdominal pain may occur. Others: Cerebral hemorrhage in the eyes, splenomegaly, nasal hemorrhage, edema, headache, dizziness, fever, fatigue, arthralgia, myalgia, bitter taste in the mouth, tremor and edema of eyelid may occasionally be associated with epoetin-α therapy. Studies analyzed to date indicate that epoetin-α is generally well tolerated. The adverse reactions reported are frequent sequelae from patient's disease, and are not necessarily attributable to epoetin-α therapy. Chronic Renal Failure Patients: In the epoetin-α studies in patients on dialysis (N=567), the incidence of the most frequently reported adverse reactions were: Hypertension (0.75%), headache (0.4%), tachycardia (0.31%), nausea/vomiting (0.26%), clotted vascular access (0.25%), shortness of breath (0.14%), hyperkalemia (0.11%) and diarrhea (0.11%). Other reported reactions occurred at a rate of <0.1% of reactions per patient per year. Reactions reported to have occurred within several hours after administration of Epokine were rare, mild and transient, and included flu-like symptoms eg, arthralgias and myalgias. In all studies analyzed to date, Epokine administration was generally tolerated, irrespective of the route of administration.
Drug Interactions Epokine is potentiated by hematinic agents.
Pregnancy Category (US FDA)
Category C: Either studies in animals have revealed adverse effects on the fetus (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.
Caution For Usage
Do not dilute or administer in conjunction with other drug solutions. Administer Epokine after dialysis in patients on dialysis and slowly inject for up to 5 min longer in patients with flu-like symptoms. Epokine should not be administered by IV infusion.
Storage
Store at 2-8°C. Protect from light. Shelf-Life: 24 months.
Active ingredient: epoetin beta Recormon is provided as lyophilisate and solvent for solution for injection, as lyophilisate and solvent for solution for injection in cartridge, and as solution for injection in pre-fi lled syringes. The reconstituted product is a colorless, clear to slightly opalescent solution. It also contains the following excipients: Urea, sodium chloride, polysorbate 20, sodium
the refrigerator and store it at room temperature (not above 25°C) for one single period of up to 5 days. Leaving the reconstituted solution outside the refrigerator should be limited to the time necessary for preparing the injections. Chemical and physical in-use stability of the reconstituted solution has been demonstrated for one month at 2°C - 8°C. Powder and solvent for solution for injection in cartridge: For the purpose of ambulatory use, the patient may remove the cartridge not yet inserted into the Reco-Pen from the refrigerator and store it at room temperature (not above 25°C) for one single period of up to 5 days. Chemical and physical in-use stability of the reconstituted solution has been demonstrated for one month at 2°C-8°C. After insertion into the Reco-Pen, the cooling chain may only be interrupted for administration of the product. Solution for injection in pre-fi lled syringes: For the purpose of ambulatory use, the patient may remove the product from the refrigerator and store it at room temperature (not above 25°C) for one single period of up to 3 days.
For all reconstituted formulations, the cooling chain may only be interrupted for administration
of the product. Shelf-Life: 2 years.
Special Instructions
for Use, Handling and
Disposal
Lyophilisate and solvent for solution for injection:
Incompatibilities
This medicinal product must not be diluted or mixed with other medicinal products except those
mentioned above
Instructions for use and handling and disposal
Recormon Multidose is supplied as a powder for solution for injection in vials. This is dissolved
with the contents of the accompanying solvent ampoule by means of a reconstitution and
withdrawal device according to the instructions given below. Only solutions which are clear or
slightly opalescent, colorless and practically free of visible particles may be injected. Do not use
glass materials for injection, use only plastic materials. This is a multidose preparation from
which different single doses can be withdrawn over a period of 1 month after dissolution. To
avoid the risk of contamination of the contents always observe aseptic techniques (i.e. use
disposable sterile syringes and needles to administer each dose) and strictly follow the handling
instructions below. Before withdrawing each dose disinfect the rubber seal of the withdrawal
device with alcohol to prevent contamination of the contents by repeated needle
insertions.
Preparation of Recormon Multidose solution
1. Take the vial with the freeze-dried substance out of the package. Write the date of
reconstitution and expiry on the label (expiry is 1 month after reconstitution).
2. Remove the plastic cap from the vial.
3. Disinfect the rubber seal with alcohol.
4. Take the reconstitution and withdrawal device (which allows sterile air exchange) out of the
blister and remove the protective cover from the spike.
5. Attach the device to the vial until the snap lock clicks home
6. Put the green needle on the syringe contained in the package and remove the needle cover.
7. Hold the OPC (One-Point-Cut) ampoule with the blue point upwards. Shake or tap the ampoule
to get any fl uid in the stem into the body of the ampoule. Take hold of the stem and snap off
away from you. Withdraw all the solvent into the syringe. Disinfect the rubber seal of the device
with alcohol.
8. Penetrate the seal with the needle to a depth of about 1 cm and slowly inject the solvent into
the vial. Then disconnect the syringe (with needle) from the device.
9. Swirl the vial gently until the powder has dissolved. Do not shake. Check that the solution is
clear, colorless and practically free from particles. Put the protective cap on the top of the device.
10. Before and after reconstitution Recormon Multidose must be stored at +2° to +8°C
(refrigerator).
Preparation of a single injection
1. Before withdrawing each dose disinfect the rubber seal of the device with alcohol.
2. Place a 26G needle onto an appropriate single-use syringe (max.1 ml).
3. Remove the needle cover and insert the needle through the rubber seal of the device.
Withdraw Recormon solution into the syringe, expel air from the syringe into the vial and adjust
the amount of Recormon solution in the syringe to the dose prescribed. Then disconnect the
syringe (with needle) from the device.
4. Replace the needle by a new one (the new needle should have the size which you normally use
for injections).
5. Remove the needle cover and carefully expel air from the needle by holding the syringe
vertically and gently pressing the plunger upwards until a bead of liquid appears at the needle tip.
For subcutaneous injection, clean the skin at the site of injection using an alcohol wipe. Form a
skin fold by pinching the skin between the thumb and the forefinger. Hold the syringe near to the
needle and insert the needle into the skin with a quick, firm action. Inject Recormon solution.
Withdraw the needle quickly and apply pressure over the injection site with a dry, sterile pad.
Any unused product or waste material should be disposed of in accordance with local
requirements.
Lyophilisate and solvent for solution for injection in cartridge:
Incompatibilities
Recormon in cartridge should only be used with the Reco-Pen. In the absence of compatibility
studies, this medicinal product should not be mixed with other medicinal products.
Instructions for use and handling and disposal This Recormon presentation is a two-chamber
cartridge containing powder for solution for injection and preserved solution. The ready-to-use
solution is prepared by inserting the cartridge into the Reco-Pen. Prior to this a needle should be
attached to the Reco-Pen. Only solutions which are clear or slightly opalescent, colorless and
practically free of visible particles may be injected. Please observe the instructions for use which
are delivered with the Reco-Pen. Any unused product or waste material should be disposed of in
accordance with local requirements.
Solution for injection in pre-fi lled syringes:
Incompatibilities
In the absence of compatibility studies, this medicinal product should not be mixed with other
medicinal products.
Instructions for use and handling and disposal
First wash your hands!
1. Remove one syringe from the pack and check that the solution is clear, colorless and practically
free from visible particles. Remove the cap from the syringe.
2. Remove one needle from the pack, fi x it on the syringe and remove the protective cap from
the needle.
3. Expel air from the syringe and needle by holding the syringe vertically and gently pressing the
plunger upwards. Keep pressing the plunger until the amount of Recormon in the syringe is as
prescribed.
4. Clean the skin at the site of injection using an alcohol wipe. Form a skin fold by pinching the
skin between thumb and fore finger. Hold the syringe barrel near to the needle, and insert the
needle into the skin fold with a quick, firm action. Inject the Recormon solution. Withdraw the
needle quickly and apply pressure over the injection site with a dry, sterile pad. This medicinal
product is for single use only. Any unused product or waste material should be disposed of in