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.

epoetin beta

Available Brands

Recormon Neorecormon

Recormon

Manufacturer Roche

Distributor Zuellig

Contents/Description

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

dihydrogen phosphate, sodium monohydrogen phosphate, calcium chloride, glycine, leucine,

isoleucine, threonine, glutamic acid and phenylalanine.

Epoetin β is also known as rhEPO or recombinant human erythropoietin.

Indications

Treatment of anemia associated with chronic renal failure (renal anemia) in patients on dialysis.

Treatment of symptomatic renal anemia in patients not yet undergoing dialysis.

Prevention of anemia of prematurity in infants and in adult patients with solid tumors and

treated with chemotherapy prone to induce anemia

MIMS Class Haematopoietic Agents

ATC Classification B03XA01 - erythropoietin ; Belongs to the class of other antianemic preparations.

Presentation/Packing

Pre-fi lled syringes: Recormon 500 IU, 1000 IU, 2000 IU, 3000 IU, 4000 IU, 5000 IU, 6000 IU, 10,000 IU, 20,000 IU, 30,000 IU Recormon Multidose vials: 1 vial with powder for solution for injection and 1 ampoule with preserved solvent, 1 reconstitution and withdrawal device, 1 needle 21 G 2, 1 disposable syringe (10 ml or 5ml). Recormon Cartridges for Reco-Pen: 1 or 3 two-chamber cartridges Pen needles

Mechanism of Action

Pharmacology: Epoetin β is identical in its amino acid and carbohydrate composition to

erythropoietin that has been isolated from the urine of anemic patients. Erythropoietin is a

glycoprotein that stimulates the formation of erythrocytes from precursors of the stem cell

compartment. It acts as a mitosis-stimulating factor and differentiation hormone.

Clinical / Effi cacy Studies: The biological efficacy of epoetin β has been demonstrated after IV

and SC administration in various animal models in vivo (normal and uremic rats, polycythemic

mice, dogs). After administration of epoetin β, the number of erythrocytes, the Hb values and

reticulocyte counts increase as well as the 59Fe-incorporation rate. Investigations in cell cultures

of human bone marrow cells showed that epoetin β stimulated erythropoiesis specifically and

does not affect leukopoiesis. Cytotoxic actions of epoetin β on bone marrow or on human skin

cells were not detected. Neither preclinical nor clinical investigations have shown any influence

of epoetin β on tumor progression. After single-dose administration of epoetin β, no effects on

behavior or locomotor activity of mice and circulatory or respiratory function of dogs were

observed.

There are no indications of development of neutralizing antibodies to epoetin β in humans.

Pharmacokinetics:

Absorption

After subcutaneous administration of epoetin beta to uremic patients, the protracted absorption

results in a serum concentration plateau, whereby the maximum concentration is reached after

an average of 12 - 28 hours.

Bioavailability of epoetin beta after subcutaneous administration is between 23 and 42% as

compared with intravenous administration.

Distribution

Pharmacokinetic investigations in healthy volunteers and uremic patients show that the

distribution volume corresponds to one to two times the plasma volume.

Elimination

Pharmacokinetic investigations in healthy volunteers and uremic patients show that the half-life

of intravenously administered epoetin beta is between 4 and 12 hours. After subcutaneous

administration of epoetin beta to uremic patients, the terminal half-life is higher than after

intravenous administration, with an average of 13 - 28 hours

Dosage

Lyophilisate and solvent for solution for injection:

The multidose preparation can be used for several patients. To avoid the risk of cross-infection

always follow aseptic techniques and use disposable sterile syringes and needles for each

administration.

Lyophilisate and solvent for solution for injection in cartridge:

Recormon in cartridge should only be used with the Reco-Pen.

Solution for injection in pre-fi lled syringe:

The Recormon pre-fi lled syringe is ready for use. Under no circumstances should more than one

dose be administered per syringe; the medicinal product is for single use only.

Treatment of patients with anemia due to chronic kidney disease

The reconstituted solution can be administered subcutaneously or intravenously. In case of

intravenous administration, the solution should be injected over approx. 2 minutes, e.g. in

hemodialysis patients via the arterio-venous fi stula at the end of dialysis.

For non-hemodialysed patients, subcutaneous administration should always be preferred in

order to avoid puncture of peripheral veins.

In CKD patients, the aim of treatment is to reach a target Hb level of 10-12 g/dl. An Hb level of 12

g/dl should not be exceeded. If the rise in hemoglobin is greater than 2 g/dl (1.3 mmol/l) in 4

weeks, an appropriate dose reduction should be considered.

In the presence of hypertension or existing cardiovascular, cerebrovascular or peripheral

vascular diseases, the weekly increase in Hb and the target Hb should be determined individually

taking into account the clinical picture. Patients should be monitored closely to ensure that the

lowest dose of Recormon is used to provide adequate control of the symptoms of anemia.

Treatment with Recormon is divided into two stages.

1. Correction phase

- Subcutaneous administration (all dosage forms):

The initial dosage is 3 x 20 IU/kg body weight per week. The dosage may be increased every 4

weeks by 3 x 20 IU/kg per week if the increase of Hb is not adequate (< 0.25 g/dl per week).

The weekly dose can also be divided into daily doses.

- Intravenous administration (powder and solvent for solution for injection and pre-fi lled syringes

only):

The initial dosage is 3 x 40 IU/kg per week. The dosage may be raised after 4 weeks to 80 IU/kg -

three times per week - and by further increments of 20 IU/kg if needed, three times per week,

at monthly intervals.

For both routes of administration, the maximum dose should not exceed 720 IU/kg per week.

2. Maintenance phase

To maintain a target Hb value of approximately 10-12 g/dl, the dosage is initially reduced to half

of the previously administered amount. Subsequently, the dose is adjusted at intervals of two

to four weeks individually for the patient (maintenance dose). In the case of subcutaneous

administration, the weekly dose can be given as one injection per week or in divided doses

three or seven times per week. Patients who are stable on a once weekly dosing regimen may be

switched to once every two weeks administration. In this case dose increases may be necessary.

Treatment with Recormon is normally a long-term therapy. It can, however, be interrupted, if

necessary, at any time. Data on the once weekly dosing schedule are based on clinical studies

with a treatment duration of 24 weeks.

Results of clinical studies in children have shown that, on average, the younger the patients, the

higher the Recormon doses required. Nevertheless, the recommended dosing schedule should

be followed as the individual response cannot be predicted.

Contraindications

Poorly controllable hypertension and known hypersensitivity to any of the constituents of

Recormon. Benzoic acid is contained in the cartridge and Multidose vials.

Special Precautions

Therapy with Recormon should be initiated by physicians experienced in the above mentioned

indications. As anaphylactoid reactions were observed in isolated cases, it is recommended that

the first dose be administered under medical supervision.

Recormon should be used with caution in the presence of refractory anemia with excess blasts in

transformation, epilepsy, thrombocytosis and chronic liver failure.

Severe aluminium overload due to treatment of renal failure may compromise the effectiveness

of Recormon. Recormon contains phenylalanine as an excipient. Therefore this should be taken

into consideration in patients affected with severe forms of phenylketonuria.

The indication for Recormon treatment of nephrosclerotic patients not yet undergoing dialysis

should be defined individually as a possible acceleration of progression of renal failure cannot be

ruled out with certainty.

Lack of effect: The most common reasons for incomplete response to ESAs (erythropoiesis-

stimulating agents) are iron defi ciency and chronic infl ammation (e.g. due to uremia or

advanced metastatic cancer). The following conditions may also compromise the effectiveness of

ESAs therapy: chronic blood loss, bone marrow fibrosis, severe aluminium overload due to

treatment of renal failure, folic acid or vitamin B12 defi ciencies, and hemolysis. If all the

conditions mentioned are excluded and the patient has a sudden drop of hemoglobin associated

with reticulocytopenia and anti-erythropoietin antibodies, examination of the bone marrow for

the diagnosis of Pure Red Cell Aplasia (PRCA) should be considered. If PRCA is diagnosed, therapy

with epoetin beta must be discontinued and patients should not be switched to another ESA.

In CKD patients and patients with cancer receiving chemotherapy an increase in blood pressure

(hypertensive episodes) or aggravation of existing hypertension, especially in cases of rapid Hb

increase can occur. Increases in blood pressure can be treated with antihypertensive drugs. If

blood pressure rises cannot be controlled by drug therapy, a transient interruption of Recormon

therapy is recommended.

Laboratory Tests: Platelet counts and hematocrit/hemoglobin levels should be monitored at

regular intervals in all patients In patients with chronic kidney disease, serum potassium

elevation has been reported in patients receiving Recormon, though causality has not been

established. If an elevated or rising potassium level is observed then consideration should be

given to interrupting Recormon administration until the level has been corrected.

In CKD patients there may be a moderate dose-dependent rise in the platelet count within the

normal range during treatment with Recormon, especially after intravenous administration. This

regresses during the course of continued therapy. It is recommended that the platelet count be

monitored regularly during the first 8 weeks of therapy.

Use in pregnancy & lactation: Animal studies revealed that no teratogenic effects occur under

therapeutic conditions. There is no adequate experience in human pregnancy and lactation.

Recormon should only be used during pregnancy and lactation if the potential benefit justifies the

potential risk.

Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use

machines have beenperformed.

Adverse Drug

Reactions

Cardiovascular System: Anemic Patients with Chronic Renal Failure: The most frequent adverse

reaction during treatment with Recormon is an increase in blood pressure or aggravation of

existing hypertension, especially in cases of rapid PCV increase. These increases in blood

pressure can be treated with drugs. If blood pressure rises cannot be controlled by drug therapy,

a transient interruption of Recormon therapy is recommended.

Particularly at the beginning of therapy, regular monitoring of blood pressure is recommended,

including between dialyses.

Hypertensive crisis with encephalopathy-like symptoms (eg, headaches and confused state,

sensorimotor disorders eg, speech disturbance or impaired gait, up to tonoclonic seizures) may

occur, also in individual patients with otherwise normal or low blood pressure. This requires the

immediate attention of a physician and intensive medical care. Particular attention should be

paid to sudden stabbing migraine-like headaches as a possible warning sign.

Frequently, an increase in the heparin dose during hemodialysis is required as a result of the

increased packed cell volume. Occlusion of the dialysis system is possible if heparinization is not

optimum. Shunt thromboses may occur, especially in patients who have a tendency to

hypotension or whose arteriovenous fistulae exhibit complications (eg, stenoses, aneurysms).

Early shunt revision and thrombosis prophylaxis by administration of acetylsalicylic acid, for

example, should be considered in CKD patients at risk of shunt thrombosis.

In most cases, a fall in serum ferritin values simultaneous with a rise in packed cell volume is

observed. Therefore, oral iron substitution of 200-300 mg Fe2+/day is recommended in all

patients with serum ferritin values <100 mcg/L or transferrin saturation <20%.

In isolated cases, transient increases in serum potassium and phosphate levels have been

observed. These parameters should be monitored regularly.

Others: Rarely, skin reactions eg, rash, pruritus, urticaria or injection site reactions may occur. In

isolated cases, anaphylactoid reactions have been reported. However, in controlled clinical

studies no increased incidence of hypersensitivity reactions was found.

Drug Interactions

The clinical results obtained so far do not indicate any interaction of Recormon with other

substances.

Incompatibilities: To avoid incompatibility or loss of activity, do not mix with other drugs or

infusion solutions.

Storage

Store the product continuously in a refrigerator at a temperature between 2°C and 8°C. Keep the

vial/cartridge/pre-fi lled syringe in the outer carton, in order to protect from light.

Lyophilisate and solvent for solution for injection: For the purpose of ambulatory use, the patient may remove the unreconstituted product from

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

accordance with local requirements.