Consumer medicine information

Recombinate Powder for injection

Octocog alfa

BRAND INFORMATION

Brand name

Recombinate Powder for injection

Active ingredient

Octocog alfa

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Recombinate Powder for injection.

What is in this leaflet?

This leaflet answers some common questions about the RECOMBINATE. It does not contain all of the available information. All medicines have risks and benefits. Your doctor has weighed the risks against the benefits for you by using RECOMBINATE.

It does not take the place of talking to your doctor or pharmacist. If you have any concerns about having this medicine, ask your doctor or pharmacist.

What RECOMBINATE is used for?

RECOMBINATE belongs to the group of medicines called blood coagulation factor VIII.

It is used for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). This preparation does not contain von Willebrand factor and is therefore not indicated in von Willebrand’s disease.

RECOMBINATE is a recombinant-derived factor VIII, which has been successfully shown to correct factor VIII deficiency. Plasma derived factor VIII has also been used for the same purpose, but due to a possible transmission of blood-borne viral impurity in the product, it is now replaced by a recombinant derived factor VIII.

How does RECOMBINATE work?

Under a normal physiological condition, factor VIII is essential for blood clotting and maintenance of bleeding episode. Individuals with haemophilia A disease, a sex-linked hereditary disorder of blood coagulation, have a decreased factor VIII in their blood circulation. As a result of factor VIII deficiency, the individual with this disease may lead to a heavy bleeding into joints, muscles or internal organ, either spontaneously or resulted from an accidental or surgical trauma.

The property of RECOMBINATE is similar with that of plasma derived factor VIII. Thus, it works in the same way as factor VIII that is normally present in a healthy individual, a replacement therapy.

Before you are given the RECOMBINATE

RECOMBINATE should not be given to you if:

  • you are allergic (hypersensitive) to mouse, hamster proteins or any other ingredients in this product.
  • you have tendency of allergic reaction or hypersensitivity to any human derived protein injection. Some of the symptoms of an allergic reaction may include skin rash, swelling of the face, lips or tongue, which may cause difficulty swallowing or shortness of breath.
  • the expiry date printed on the pack has passed.

You must tell your doctor if you:

  • have any other illness
  • are taking any prescription medicine or any other medicines purchased from a pharmacy, health food store or supermarket. Some medicines and RECOMBINATE may interfere with each other.

You must tell your doctor, if you are pregnant, planning to become pregnant or breast-feeding.

The use of RECOMBINATE during pregnancy is not recommended, due to insufficient information in supporting of such usages, because haemophilia is rare in female (haemophilia is male sex-linked hereditary congenital disorder). If there is a need to consider the use of this product during your pregnancy or breast feeding, your doctor will discuss the risks and benefit with you.

How RECOMBINATE is given

How much is given:

Your doctor will decide how much RECOMBINATE will be given to you, which depends on your need and condition. Each individual will receive a different dosage, which in itself may vary between doctor visits. The dose you receive will be based on:

  1. body weight;
  2. the amount of factor VIII your body is able to make;
  3. how much, how often and which sites (knees, muscle, etc) of your body are bleeding;
  4. whether your body may build up antibodies to this medicine. After a while your body may build up these antibodies, leading to a less effective treatment than the usual.

If you miss/forget your injection:

Proceed with the next administration immediately, and continue at regular intervals as advised by your doctor. Do not take a double dose to make up the forgotten dose.

Reconstitution - (Use aseptic technique)

  1. Bring RECOMBINATE (dry concentrate) and Sterile Water for Injection, USP (diluent) to room temperature.
  2. Remove caps from the concentrate and diluent vial.
  3. Cleanse stoppers with germicidal solution and allow to dry prior to use.
  4. Remove protective covering from one end of double-ended needle and insert exposed needle through the centre of diluent stopper.
  5. Remove protective covering from other end of the double-ended needle. Invert diluent vial over the upright RECOMBINATE vial, then rapidly insert free end of the needle through the RECOMBINATE vial stopper at its centre. The vacuum in the vial will draw in the diluent.
  6. Disconnect the two vials by removing the needle from the diluent vial stopper, then remove the needle from the RECOMBINATE vial. Swirl gently until all the material is dissolved. Be sure that the RECOMBINATE is completely dissolved, otherwise the active material will be removed by the filter needle.

Method of Administration (use aseptic technique):

RECOMBINATE is usually administered in the hospital. However, some individuals may be trained to use RCOMBINATE at home. It is administered by intravenous injection.

If you are injecting at home, take the dry medicine vial and the small vial of water out of the refrigerator and let them come to room temperature (15°C to 30°C). Visually examine the dry medicine vial and contents, and do not use if there is any sign of damage or discolouration. The dry medicine should appear off-white to faint yellow.

After cleaning the stoppers, use a plastic disposable syringe (not glass) and a double-ended needle to inject the water into the dry medicine, aiming the water against the wall of the dry medicine container. This will prevent foaming. Dissolve the medicine by swirling. Do not shake the container, as it contains a surfactant, polysorbate 80, which causes foaming upon shaking.

After preparation, the medicine should be used immediately or at least within 3 hours after it is prepared. Do not refrigerate after reconstitution. Please refer to the directions on the package or talk to your doctor.

Do not reuse syringes and needles. Place them in a puncture resistant disposable container, or otherwise dispose of them as directed by your doctor. Likewise, discard any unused solution as directed by your doctor.

Case of overdose

No symptoms of overdose with RECOMBINATE have been reported

While you are treated with RECOMBINATE

Discuss with your doctor the progress you have experienced after the treatment, especially during the first few days. As RECOMBINATE is given in a hospital, your healthcare professional will take records of the progress and unexpected reactions.

ADVERSE EFFECTS

Adverse effects from the use of RECOMBINATE are rare. However, if you suffer from any of the following symptoms, stop the infusion immediately and alert your doctor.

Seek medical attention immediately if any of the following side effects occur, as these may mean that you are having a severe allergic response to the medicine:

  • fast or irregular breathing
  • shortness of breath
  • troubled breathing
  • tightness in the chest and/or wheezing
  • changes in facial skin colour
  • puffiness or swelling of the eyelids or around the eyes or face
  • skin rash
  • dizziness
  • abnormal sensation
  • low blood pressure
  • loss of consciousness
  • hives
  • itching

Also check with your doctor if any of the following less common or rare side effects occur:

  • chills
  • fever
  • nausea
  • tenderness
  • swelling
  • pain and skin discolouration at the injection site plus warmth or noticeable veins over affected area
  • unusual lethargy or weakness
  • chest tightness
  • coughing
  • short of breath
  • low blood pressure
  • trembling
  • unusual bleeding or bruising
  • fast heart beat
  • bluish discolouration of the skin
  • chest pain or discomfort

Other side effects may occur that usually do not need medical attention. These side effects are less common and may go away during treatment as your body adjusts to the medicine. However, please see your doctor if any of the following side effects continue:

  • burning
  • stinging
  • dizziness or light-headedness
  • headache
  • nose-bleed
  • swelling at the injection site
  • dry mouth or bad taste
  • redness of the face
  • vomiting
  • perspiration
  • ear infection or hearing problems
  • cold fingers and toes
  • rash
  • tingling or numbness of the hands or feet (pins and needles)

Please consult your doctor if you experience any of the unwanted effects as listed above.

Product descriptions

What RECOMBINATE looks like?

It is presented in a white to cream colour powder in a single dose glass vial accompanied by sterile water for injection in glass vial for reconstitution. The package also contains a double-ended needle and package insert.

What is in RECOMBINATE?

The active ingredient in RECOMBINATE is antihaemophilic factor [Recombinant Coagulation Factor VIII (rhc)], produced by recombinant technology. Three strengths, 250 IU, 500 IU, and 1000 IU of RECOMBINATE are commercially available.

The amounts of each component of the excipients in all strengths are the same. Thus, after reconstitution with 10 mL of Water for Injections each vial contains in maximum amounts: human Albumin (125 mg), Sodium Chloride (105 mg), Histidine (85 mg), Macrogol 3350 (15 mg), Calcium Chloride (7.3 mg), Polysorbate 80 (1.5 µg/IU).

How to store RECOMBINATE

RECOMBINATE is a protein preparation; therefore, it should be stored 2 - 8°C in a refrigerator (do not freeze) or store below 30°C. After reconstitution, it should not be refrigerated and must be administered within 3 hours. Avoid freezing to prevent damage to the diluent bottle.

Where can you get more information?

You can get more information from your doctor or pharmacist.

Name and address of the Sponsor

RECOMBINATE is manufactured by:

Baxalta US Inc
Westlake Village,
CA 91362, USA,

Distributed in Australia by:

Baxalta Australia Pty Ltd
1 Baxter Drive,
Old Toongabbie NSW 2148, Sydney

The last revision: May 2015

Baxalta and RECOMBINATE is a trademark of Baxalta Incorporated.

BRAND INFORMATION

Brand name

Recombinate Powder for injection

Active ingredient

Octocog alfa

Schedule

Unscheduled

 

Name of the medicine

Octocog alfa (rAHF, factor VIII (rch)).

Excipients.

Maximum amounts when reconstituted with the appropriate volume of diluent (10 mL): albumin (human) 125 mg, macrogol 3350 15 mg, sodium chloride 105 mg, histidine 85 mg, calcium chloride 7.3 mg. Polysorbate 80 (1.5 microgram/factor VIII IU, i.e. 1.5 mg in Recombinate 1,000 IU, 0.750 mg in 500 IU and 0.375 mg in 250 IU presentations) is present as an impurity of the manufacturing process.

Description

The active ingredient in Recombinate, octocog alfa (antihaemophilic factor (recombinant)), is a glycoprotein synthesised using genetically engineered Chinese hamster ovary cells (CHO). The CHO cells secrete recombinant factor VIII (rFVIII) into a cell culture medium, which is then purified by a series of chromatography columns. The rFVIII is selectively isolated in a purification matrix prepared by immobilisation of a monoclonal antibody directed to factor VIII. The rFVIII produced has the same biological effects as natural human factor VIII. Recombinant von Willebrand factor (rVWF) is coexpressed with the rFVIII and helps to stabilise it.
Recombinate is a sterile, non-pyrogenic, off-white to faint yellow lyophilised powder preparation of concentrated recombinant Factor VIII (rAHF) for intravenous injection and is available in single dose vials containing 250, 500 and 1000 IU (International Units) nominally per vial.

Pharmacology

General.

Under normal physiological condition, factor VIII is essential for blood clotting and haemostasis. The activated factor VIII (FVIIIa) acts as cofactor for activating factor IX to FIXa, cascading to activate factor X to FXa. By the actions of the activated factors Va and Xa, the circulating prothrombin is converted into thrombin. Subsequently, thrombin converts fibrinogen to fibrin monomer cascading to formation of linear fibrin polymer. By the action of factor XIII the fibrin monomer is cross linked to form fibrin clots leading to the arrest of the bleeding episodes.
In patients with haemophilia A (classical haemophilia), a sex linked hereditary disorder of blood coagulation, the level of circulating factor VIII is decreased, leading to profuse bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. The use of plasma derived or recombinant derived factor VIII has been shown successfully to correct this deficiency. Thus, the plasma derived and recombinant derived factor VIII has the same pharmacological actions.

Clinical Trials

Pharmacokinetic studies on sixty-nine (69) patients revealed the circulating mean half-life of Recombinate to be 14.6 ± 4.9 hours (n = 67), which was not significantly different statistically from Baxter Healthcare Corporation's plasma derived Hemofil M (antihaemophilic factor (human) method M, monoclonal purified). The mean half-life of Hemofil M was 14.7 ± 5.1 hours (n = 61). The actual baseline recovery observed with Recombinate was 123.9 ± 47.7 IU/dL (n = 23) which is significantly higher than the actual Hemofil M baseline recovery of 101.7 ± 31.6 IU/dL (n = 61). However, the calculated ratio of actual to expected recovery with Recombinate (121.2 ± 48.9%) is similar to that of Hemofil M (123.4 ± 16.4%).
The clinical study of Recombinate in previously treated patients involved observations made on a study group of 69 patients. These individuals received from 20,914 to 1,383,063 IU over the 48 month study. Patients were given a total of 17,700 infusions totalling 28,090,769 IU Recombinate. These patients were successfully treated for bleeding episodes on a demand basis and also for the prevention of bleeds. Spontaneous bleeding episodes successfully managed include haemarthrosis, soft tissue and muscle bleeds. Management of haemostasis in surgical procedures was also evaluated. A total of 24 procedures in 13 patients were performed during this study. These included minor (e.g. tooth extraction) and major (e.g. liver transplant, thoracotomy, bilateral osteotomies). Haemostasis was maintained perioperatively and postoperatively with individualised factor VIII replacement.
A study of Recombinate in previously untreated patients was also performed. The study group comprised seventy-nine (79) patients of whom seventy-six (76) had received at least one infusion of Recombinate. In total, this group had been given 12,209 infusions totalling 11,277,043 IU Recombinate. Haemostasis was appropriately managed in spontaneous bleeding episodes, intracranial haemorrhage and surgical procedures.

Indications

Recombinate is indicated for use in haemophilia A (classical haemophilia) for the prevention and control of haemorrhagic episodes1. Patients with haemophilia A may be treated with Recombinate as perioperative management. Recombinate is not indicated in von Willebrand's disease.

Contraindications

Known hypersensitivity to the active substance, excipients or to mouse, hamster or bovine protein may be a contraindication to the use of Recombinate.

Precautions

General.

Allergic type hypersensitivity reactions, including anaphylaxis, have been observed with Recombinate and have been manifested by dizziness, rash, flushing, angioedema/ face swelling, urticaria, pruritis, loss of consciousness, dyspnea, hypotension, pallor, pyrexia, paresthesia, and nausea.

Use with caution in the following circumstances.

Patients treated with Recombinate should be carefully monitored for the development of antibodies to factor VIII by appropriate clinical observations and laboratory tests. As this product contains trace amounts of mouse, hamster and bovine protein, the possibility exists that patients treated with Recombinate may develop hypersensitivity to these nonhuman mammalian proteins. The capacity for these proteins to elicit the immunological responses in animals has not been systematically examined.

Check the following before use.

Identification of the clotting defect as a factor VIII deficiency is essential prior to initiation of Recombinate treatment. Benefit will not be gained by using this treatment on other clotting defects.

Formation of antibodies to factor VIII.

Allergic type hypersensitivity reactions, including anaphylaxis, have been observed with Recombinate and have been manifested by dizziness, rash, flushing, angioedema/ face swelling, urticaria, pruritus, loss of consciousness, dyspnea, hypotension, pallor, pyrexia, paresthesia, and nausea.
The development of neutralising antibodies (inhibitors) to factor VIII, is a known complication in the treatment of patients with haemophilia A. The reported prevalence of these antibodies in patients receiving plasma derived factor VIII is 10-20%3,4,5,6,7,10,11,12. These inhibitors are invariably IgG immunoglobulins, the factor VIII procoagulant inhibitory activity of which is expressed as Bethesda Units (BU) per mL of plasma or serum3,4,5,6,7. The risk of developing inhibitors is correlated to the extent of exposure to factor VIII, the risk being highest within the first 20 exposure days, and to other genetic and environmental factors. The risk for inhibitor development depends on a number of factors relating to the characteristics of the patient (e.g. type of the factor VIII gene mutation, family history, ethnicity), which are believed to represent the most significant risk factors for inhibitor formation. Inhibitors have predominantly been reported in previously untreated patients. Over the investigational period, none of the 65 previously treated individuals, without an inhibitor at entry into the study, developed an inhibitor. In the previously untreated patient group there were 66 patients with factor VIII levels less than or equal to 2% who were tested for inhibitor after treatment with Recombinate. Of this group, 12 individuals developed detectable inhibitor and, of these, 3 patients showed a titre greater than 10 BU. Patients treated with factor VIII should be carefully monitored for the development of antibodies to factor VIII by appropriate clinical observations and laboratory tests.

Formation of antibodies to mouse, hamster or bovine protein.

Patients treated with Recombinate may develop hypersensitivity to trace amounts of nonhuman mammalian proteins present, these being mouse protein (maximum 0.1 nanogram/IU Recombinate activity), hamster protein (maximum 1.5 nanogram CHO protein/IU Recombinate activity) and bovine protein (maximum 1 nanogram bovine serum albumin/IU Recombinate activity).

Carcinogenicity/ mutagenicity.

Long-term animal studies have not been performed to evaluate carcinogenic potential. Testing for mutagenicity conducted in vitro at doses considerably exceeding plasma concentrations of factor VIII, and in vivo at doses up to ten times the expected maximum clinical dose, did not detect reverse mutations, chromosomal aberrations nor an increase in micronuclei in bone marrow polychromatic erythrocytes.

Effects on fertility.

Animal studies to determine the effect of Recombinate on fertility have not been conducted.

Use in pregnancy.

(Category B2)
Animal reproduction studies have not been conducted with Recombinate. As it is not known whether Recombinate can cause foetal damage, Recombinate should be given to a pregnant woman only if clearly needed. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing Recombinate.

Use in lactation.

It is not known whether Recombinate or its metabolites are excreted in human milk. Nursing is not recommended in women being treated with Recombinate. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing Recombinate.

Paediatric use.

Recombinate is appropriate for use in children of all ages, including the newborn. Safety and efficacy have been determined in both previously treated and previously untreated children (see Precautions).

Effects on ability to drive and use machines.

There is no information of the effects of Recombinate on the ability to drive or operate an automobile or other heavy machinery.

Effects on laboratory tests.

It is recommended that appropriate laboratory testing be performed on each patient's plasma at suitable intervals to ensure the maintenance of adequate factor VIII levels. In the case where bleeding is uncontrolled, these laboratory investigations may detect the presence of an inhibitor which can be quantified in terms of factor VIII IU neutralised by each mL of plasma. If the inhibitor is present at levels less than 10 BU per mL, administration of additional factor VIII may neutralise the inhibitor. Thereafter, the administration of additional factor VIII international units should elicit the predicted response. The control of factor VIII levels by laboratory assays is necessary in these situations.

Animal toxicity.

Repeat dose toxicity studies, with intravenous administration of Recombinate to rats and cynomolgus monkeys, have been limited to duration of 4 weeks.

Interactions

None known. No interaction studies have been performed with Recombinate.

Adverse Effects

Adverse effects from clinical trials.

Adverse reactions to Recombinate are rare (less than 1 report per 106 IU used in clinical studies). Adverse reactions reported in clinical studies have included the following.

Gastrointestinal disorders.

Nausea, vomiting.

General disorders and administration site conditions.

Chills, fatigue, pyrexia, chest tightness, coughing, diaphoresis.

Infections and infestations.

Ear infection.

Investigations.

Acoustic simulation tests abnormal.

Muscloskeletal and connective tissue disorders.

Pain in extremity.

Nervous system disorders.

Dizziness, tremor.

Respiratory, thoracic and mediastinal disorders.

Pharyngolaryngeal pain, dyspnoea (moderate to severe).

Skin and subcutaneous tissue disorders.

Hyperhydrosis, pruritis, rash, rash maculopapular, burning sensation, erythema, urticaria, cyanosis.

Vascular disorders.

Epistaxis, flushing, haematoma, hypotension, pallor, peripheral coldness.
During the PTP (previously treated patients) study, none of the 71 subjects developed de novo evidence of factor VIII inhibitor. However, during the phase II/III portion of the study, 1 subject with a history of inhibitors exhibited inhibitor activity at 6 months (0.8 Bethesda Units [BU]), which resolved by 9 months. One other subject in this study had detectable factor VIII inhibitor at baseline (1.26 BU) and exhibited an anamnestic response at 6 months (10.3 BU). During study 039801, none of the 34 treated subjects developed a factor VIII inhibitor.
During the PUP (previously untreated patients) study, 22 of the 73 evaluable subjects developed inhibitors to factor VIII. Of these, 13 subjects displayed no detectable factor VIII inhibitors at study exit.
The presence of albumin (human) in Recombinate is associated with the following allergic reactions: nausea, fever, chills and urticaria. Reports of such reactions, however, are extremely rare.
Patients should be advised to discontinue use of Recombinate and seek medical advice in the event of any allergic reactions, including fever spike, hives, generalised urticaria, shortness of breath, tightness of the chest, wheezing, hypotension and anaphylaxis.

Postmarketing adverse effects.

In addition to the adverse reactions noted in clinical trials, the following adverse reactions have been reported in the postmarketing experience.

Blood and lymphatic system disorders.

Factor VIII inhibition.

Cardiac disorders.

Tachycardia, cyanosis.

Gastrointestinal disorders.

Vomiting, abdominal pain.

General disorders and administration site conditions.

Malaise, injection site reactions, chest pain, chest discomfort.

Immune system disorders.

Anaphylactic reaction, hypersensitivity.

Nervous system disorders.

Loss of consciousness, headache, paresthesia.

Respiratory, thoracic and mediastinal disorders.

Dyspnoea, cough.

Skin and subcutaneous tissue disorders.

Angioedema, urticaria, erythema.

Dosage and Administration

Recombinate is intended for intravenous administration, and not for intramuscular or other parenteral administration.
If bleeding is not controlled with the prescribed dose, the plasma level of factor VIII should be determined, and a sufficient dose of Recombinate should be administered to achieve a satisfactory clinical response. The careful control of the substitution therapy is especially important in cases of major surgery or life threatening haemorrhages. Under certain circumstances (e.g. presence of a low titer inhibitor) doses larger than those prescribed may be necessary.
Each vial of Recombinate is labelled in accordance with the World Health Organization International Standard for factor VIII concentrate with the factor VIII activity expressed in IU per vial.
The expected in vivo peak increase in factor VIII level expressed as IU/dL of plasma or % (percent) of normal can be estimated by multiplying the dose administered per kg bodyweight (IU/kg) by 2. This calculation is based on clinical findings and is supported by the data generated over time in 419 clinical pharmacokinetic studies with Recombinate in 67 patients.
This data demonstrated a peak recovery point above the preinfusion baseline of approximately 2.0 IU/dL per IU/kg bodyweight.
Examples (assuming patient's baseline factor VIII level is at < 1%):
(1) A dose of 1,750 IU Recombinate administered to a 70 kg patient, i.e. 25 IU/kg bodyweight (1,750/70), should be expected to cause a peak postinfusion factor VIII increase of 25 IU/kg x 2 (IU/dL)/(IU/kg) = 50 IU/dL (50% of normal).
(2) A peak level of 70% is required in a 40 kg child. In this situation the dose would be 70 IU/dL/2 (IU/dL)/(IU/kg) x 40 kg = 1,400 IU.
Table 1 may be used as a guide for physicians.
If bleeding is not controlled with the prescribed dose, the plasma level of factor VIII should be determined and a sufficient dose of Recombinate should be administered to achieve a satisfactory clinical response. The careful control of the substitution therapy is especially important in cases of major surgery or life threatening hemorrhages. Under certain circumstances (e.g. presence of a low titer inhibitor) doses larger than those prescribed may be necessary.

Reconstitution.

Use aseptic technique.
1. Bring Recombinate (dry factor concentrate) and Sterile Water for Injection, USP (diluent) to room temperature.
2. Remove caps from concentrate and diluent vials.
3. Cleanse stoppers with germicidal solution and allow to dry prior to use. Place vial on a flat surface.
4. Remove protective covering from one end of double ended needle and insert exposed needle through the centre of the stopper.
5. Remove protective covering from other end of double ended needle. Invert diluent vial over the upright Recombinate vial, then rapidly insert free end of the needle through the Recombinate vial stopper at its centre. The vacuum in the vial will draw the diluent.
6. Disconnect the two vials by removing needle from diluent vial stopper, then remove needle from Recombinate vial. Swirl gently until Recombinate is completely dissolved, otherwise active material will be removed by the filter needle.

Note.

Do not refrigerate after reconstitution. (See Administration.)

Administration.

Use aseptic technique.
Administer at room temperature. Recombinate should be administered not more than three hours after reconstitution.

Intravenous syringe injection.

Recombinate should be inspected for particulate matter and discolouration after reconstitution and prior to administration. The solution should be colourless to faint yellow in appearance, and substantially free from foreign particles. If not, do not use the solution and notify Baxter immediately.
Plastic syringes are recommended when administering Recombinate, as proteins such as Recombinate tend to stick to the surface of all glass syringes.
1. Attach filter needle to a disposable syringe and draw back plunger to admit air into the syringe.
2. Insert needle into reconstituted Recombinate.
3. Inject air into vial and then withdraw the reconstituted material into the syringe.
4. Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously as instructed under Rate of administration.
5. If a patient is to receive more than one vial of Recombinate, the contents of multiple vials may be drawn into the same syringe by drawing up each vial through a separate unused filter needle. Please note: filter needles are intended to filter the contents of a single vial of Recombinate only.

Rate of administration.

Preparations of Recombinate should be administered at a rate that ensures the comfort of the patient, up to a maximum of 10 mL per minute. The pulse rate should be determined before and during administration of Recombinate. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.

Overdosage

No symptoms of overdose are known. The Poisons Information Centre, telephone number 131 126, should be contacted for advice on the management of an overdosage.

Presentation

Powder for injection (sterile, nonpyrogenic, off white to faint yellow, lyophilised, nominal strength designated on outer box and vial label with coloured bar), 250 IU (light blue, AUST R 65814), 500 IU (light pink, AUST R 65857), 1000 IU (light green, AUST R 65858): 1's (single dose vial in box with Sterile Water for Injection USP 10 mL, double ended needle, filter needle, package insert).

Storage

Recombinate may be stored under refrigeration at 2°C-8°C (do not freeze), or stored below 30°C. Avoid freezing to prevent damage to the diluent vial. Do not use beyond the expiration of the product. Refer to the expiry date printed on the carton box.

References

1. White GC, McMillan CW, Kingdon HS, et al: Use of recombinant antihemophilic factor in the treatment of two patients with classic hemophilia. New Eng J Med 320:166-170, 1989.
2. Kessler CM: An Introduction to Factor VIII Inhibitors: The Detection and Quantitation. Am J Med 91 (Suppl 5A):1S-5S, 1991.
3. Schwarzinger I, Pabinger I, Korninger C, Haschke F, Kundi M, Niessner H, Lechner K: Incidence of inhibitors in patients with severe and moderate hemophilia A treated with factor VIII concentrates. Am J Hematology 24:241-245, 1987.
4. Penner JA, Kelly PE: Management of patients with factor VIII or IX inhibitors. Sem Thromb Hemostasis 1:386-399, 1975.
5. Ehrenforth S, Kreuz W, Scharrer I, et al: Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet 339:594-598, 1992.
6. McMillan CW, Shapiro SS, Whitehurst D, et al: The natural history of factor VIII inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors. Blood 71:344-348, 1988.
7. Addiego JE Jr., Gomperts E, Liu S, et al: Treatment of hemophilia A with a highly purified Factor VIII concentrate prepared by Anti-FVIIIc immunoaffinity chromatography. Thrombosis and Haemostasis 67:19-27, 1992.
8. Abildgaard CF, Simone JV, Corrigan JJ, et al: Treatment of hemophilia with glycine-precipitated Factor VIII. New Eng J Med 275:471-475, 1966
9. Schimpf K, Rothman P, Zimmermann K: Factor VIII dosis in prophylaxis of hemophilia A; A further controlled study in Proc XIth Cong W.F.H. Kyoto, Japan, Academic Press, 1976, pp 363-366.
10. Gill FM: The Natural History of Factor VIII Inhibitors in Patients with Hemophilia A. Hoyer LW (ed), Factor VIII Inhibitors, N.Y. AR Liss, 1984, pp 19-29.
11. Rasi V, Ikkala E: Haemophiliacs with factor VIII inhibitors in Finland: prevalence, incidence and outcome. Br J Haematol 76:369-371, 1990.
12. Lusher JM, Salzman PM: Viral Safety and Inhibitor Development Associated with Factor VIIIC Ultra-Purified From Plasma in Hemophiliacs Previously Unexposed to Factor VIIIC Concentrates. Seminars in Hematology 27:1-7, 1990.

Poison Schedule

Unscheduled.