KOVALTRY 2000UI powder + solvent for injection medication leaflet

Kovaltry 250 IU powder and solvent for solution for injection

Kovaltry 500 IU powder and solvent for solution for injection

Kovaltry 1000 IU powder and solvent for solution for injection

Kovaltry 2000 IU powder and solvent for solution for injection

Kovaltry 3000 IU powder and solvent for solution for injection

Kovaltry 250 IU powder and solvent for solution for injection

Kovaltry contains approximately 250 IU (100 IU/1 mL) of recombinant human coagulationfactor VIII (INN: octocog alfa) after reconstitution.

Kovaltry 500 IU powder and solvent for solution for injection

Kovaltry contains approximately 500 IU (200 IU/1 mL) of recombinant human coagulationfactor VIII (INN: octocog alfa) after reconstitution.

Kovaltry 1000 IU powder and solvent for solution for injection

Kovaltry contains approximately 1000 IU (400 IU/1 mL) of recombinant human coagulationfactor VIII (INN: octocog alfa) after reconstitution.

Kovaltry 2000 IU powder and solvent for solution for injection

Kovaltry contains approximately 2000 IU (400 IU/1 mL) of recombinant human coagulationfactor VIII (INN: octocog alfa) after reconstitution.

Kovaltry 3000 IU powder and solvent for solution for injection

Kovaltry contains approximately 3000 IU (600 IU/1 mL) of recombinant human coagulationfactor VIII (INN: octocog alfa) after reconstitution.

The potency (IU) is determined using the European Pharmacopoeia chromogenic assay. The specificactivity of Kovaltry is approximately 4000 IU/mg protein.

Octocog alfa (Full length recombinant human coagulation factor VIII (rDNA)) is a purified proteinthat has 2,332 amino acids. It is produced by recombinant DNA technology in baby hamster kidneycells (BHK) into which the human factor VIII gene has been introduced. Kovaltry is prepared withoutthe addition of any human or animal derived protein in the cell culture process, purification or finalformulation.

For the full list of excipients, see section 6.1.

Powder and solvent for solution for injection

Powder: solid, white to slightly yellow.

Solvent: water for injections, a clear solution.

Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIIIdeficiency). Kovaltry can be used for all age groups.

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.

During the course of treatment, appropriate determination of factor VIII levels is advised to guide thedose to be administered and the frequency of repeated infusions. Individual patients may vary in theirresponse to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweightmay require adjustment in underweight or overweight patients.

In the case of major surgical interventions in particular, precise monitoring of the substitution therapyby means of coagulation analysis (plasma factor VIII activity) is indispensable.

The dose and duration of the substitution therapy depend on the severity of the factor VIII deficiency,on the location and extent of the bleeding and on the patient's clinical condition.

The number of units of factor VIII administered is expressed in International Units (IU), which arerelated to the current WHO standard for factor VIII products. Factor VIII activity in plasma isexpressed either as a percentage (relative to normal human plasma) or in International Units (relativeto an International Standard for factor VIII in plasma).

One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII inone mL of normal human plasma.

The calculation of the required dose of factor VIII is based on the empirical finding that1 International Unit (IU) factor VIII per kg body weight raises the plasma factor VIII activity by 1.5%to 2.5% of normal activity.

The required dose is determined using the following formula:

Required units = body weight (kg) x desired factor VIII rise (% or IU/dL) x reciprocal of observedrecovery (i.e. 0.5 for recovery of 2.0%).

The amount to be administered and the frequency of administration should always be targeted to theclinical effectiveness required in the individual case.

In the case of the following haemorrhagic events, the factor VIII activity should not fall below thegiven level (in % of normal) in the corresponding period. The following table can be used to guidedosing in bleeding episodes and surgery:

Table 1: Guide for dosing in bleeding episodes and surgery

Degree of haemorrhage/ Factor VIII level Frequency of doses (hours)/

Type of surgical procedure required (%) (IU/dL) Duration of therapy (days)

Haemorrhage Repeat every 12 to 24 hours. Atleast 1 day, until the bleeding

Early haemarthrosis, muscle 20 - 40 episode as indicated by pain isbleeding or oral bleeding resolved or healing is achieved.

More extensive 30 - 60 Repeat infusion every 12 - 24 hourshaemarthrosis, muscle for 3 - 4 days or more until pain andbleeding or haematoma acute disability are resolved.

Life threatening 60 - 100 Repeat infusion every 8 to 24 hourshaemorrhages until threat is resolved

Minor surgery Every 24 hours, at least 1 day, untilincluding tooth extraction 30 - 60 healing is achieved.

Major surgery 80 - 100 Repeat infusion every 8 - 24 hours(pre- and post- until adequate wound healing, thenoperative) therapy for at least another 7 days tomaintain a factor VIII activity of30% to 60% (IU/dL).

For long term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses foradolescents (≥ 12 years age) and adult patients are 20 to 40 IU of Kovaltry per kg body weight two tothree times per week.

In some cases, especially in younger patients, shorter dose intervals or higher doses may be necessary.

A safety and efficacy study has been performed in children of 0 - 12 years (see section 5.1).

The recommended prophylaxis doses are 20-50 IU/kg twice weekly, three times weekly or every otherday according to individual requirements. For paediatric patients above the age of 12, the doserecommendations are the same as for adults.

Kovaltry should be injected intravenously over 2 to 5 minutes depending on the total volume. The rateof administration should be determined by the patient’s comfort level (maximal rate of infusion:2 mL/min).

For instructions on reconstitution of the medicinal product before administration, see section 6.6 andthe package leaflet.

* Hypersensitivity to the active substance or to any of the excipients listed insection 6.1.

* Known allergic reactions to mouse or hamster proteins.

In order to improve traceability of biological medicinal products, the name and the batch number ofthe administered product should be clearly recorded.

Allergic type hypersensitivity reactions are possible with Kovaltry.

If symptoms of hypersensitivity occur, patients should be advised to discontinue the use of themedicinal product immediately and contact their physician.

Patients should be informed of the early signs of hypersensitivity reactions including hives,generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.

In case of shock, standard medical treatment for shock should be implemented.

The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in themanagement of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulinsdirected against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU)per mL of plasma using the modified assay. The risk of developing inhibitors is correlated to theseverity of the disease as well as the exposure to factor VIII , this risk being highest within the first50 exposure days but continues throughout life although the risk is uncommon.

The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titreposing less of a risk of insufficient clinical response than high titre inhibitors.

In general, all patients treated with coagulation factor VIII products should be carefully monitored forthe development of inhibitors by appropriate clinical observations and laboratory tests (seesection 4.2).

If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled withan appropriate dose, testing for factor VIII inhibitor presence should be performed. In patients withhigh levels of inhibitor, factor VIII therapy may not be effective and other therapeutic options shouldbe considered. Management of such patients should be directed by physicians with experience in thecare of haemophilia and factor VIII inhibitors.

In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase thecardiovascular risk.

If a central venous access device (CVAD) is required, risk of CVAD-related complications includinglocal infections, bacteraemia and catheter site thrombosis should be considered.

It is strongly recommended that every time that Kovaltry is administered to a patient, the name andbatch number of the product are recorded in order to maintain a link between the patient and the batchof the medicinal product.

The listed warnings and precautions apply both to adults and children.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially‘sodium-free’.

No interactions of human coagulation factor VIII (rDNA) products with other medicinal products havebeen reported.

Animal reproduction studies have not been conducted with factor VIII. Based on the rare occurrenceof haemophilia A in women, experience regarding the use of factor VIII during pregnancy is notavailable.

Therefore, factor VIII should be used during pregnancy only if clearly indicated.

It is unknown whether Kovaltry is excreted in human milk. The excretion in animals has not beenstudied. Therefore, factor VIII should be used during breast-feeding only if clearly indicated.

No animal fertility studies have been conducted with Kovaltry and its effect on human fertility has notbeen established in controlled clinical trials. Since Kovaltry is a replacement protein of endogenousfactor VIII, no adverse effects on fertility are expected.

If patients experience dizziness or other symptoms affecting their ability to concentrate and react, it isrecommended that they do not drive or use machines until the reaction subsides.

Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at theinfusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea,restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed andmay in some cases progress to severe anaphylaxis (including shock).

Development of antibodies to mouse and hamster protein with related hypersensitivity reactions mayoccur.

Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treatedwith factor VIII (FVIII), including with Kovaltry. If such inhibitors occur, the condition may manifestitself as an insufficient clinical response. In such cases, it is recommended that a specialisedhaemophilia centre be contacted.

The table presented below is according to the MedDRA system organ classification (SOC and

Preferred Term Level). Frequencies have been evaluated according to the following convention: verycommon (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) , rare (≥1/10,000 to<1/1,000); very rare (<1/10,000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2: Frequency of adverse drug reactions in clinical trials

MedDRA Adverse reactions Frequency

System Organ Class

Blood and lymphatic system Lymphadenopathy uncommondisorders FVIII inhibitor very common (PUPs)*uncommon (PTPs)*

Immune system disorders Hypersensitivity uncommon

Psychiatric disorders Insomnia common

Nervous system disorders Headache common

Dizziness common

Dysgeusia uncommon

Cardiac disorders Palpitation uncommon

Sinus tachycardia uncommon

Vascular disorders Flushing uncommon

Gastrointestinal disorders Abdominal pain common

Abdominal discomfort common

Dyspepsia common

Skin and subcutaneous tissue Pruritus commondisorders Rash*** common

Urticaria common

Dermatitis allergic uncommon

General disorders and Pyrexia commonadministration site conditions Injection site reactions ** common

Chest discomfort uncommon

* Frequency is based on studies with all FVIII products which included patients with severehaemophilia A. PTPs = previously treated patients, PUPs = previously untreated patients

** includes injection site extravasation, hematoma, infusion site pain, pruritus, swelling

*** rash, rash erythematous, rash pruritic, rash vesicular

A total of 236 (193 PTPs, 43 PUPs/MTPs) patients constituted the pooled safety population in thethree phase III studies in previously treated patients (PTPs), previously untreated patients (PUPs) andminimal treated patients (MTPs); LEOPOLD I, LEOPOLD II, LEOPOLD Kids studies. The mediantime on clinical trial for pooled safety population was 558 days (range 14 to 2436 days) with a medianof 183 exposure days (EDs) (range 1 to 1230 EDs).

* The most frequently reported adverse reactions in the pooled population were pyrexia, headacheand rash.

* The most frequently reported adverse reactions in the PTPs were related to potentialhypersensitivity reactions, including headache, pyrexia, pruritus, rash and abdominaldiscomfort.

* The most frequently reported adverse reaction in PUPs/MTPs was FVIII inhibitor.

The immunogenicity of Kovaltry was evaluated in PTPs and PUPs/MTPs.

During clinical trials with Kovaltry in approximately 200 pediatric and adult patients diagnosed withsevere hemophilia A (FVIII:C < 1%) with previous exposure to factor VIII concentrates ≥ 50 ED, onecase of transient low titer inhibitor (peak titer 1.0 BU/mL) occurred in a 13 year old PTP after549 EDs. The Factor VIII recovery was normal (2.7 IU/dL per IU/kg).

In the clinical studies no age-specific differences in ADR were observed except for FVIII inhibitor in

PUPs/MTPs.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

No symptoms of overdose with recombinant human coagulation factor VIII have been reported.

Pharmacotherapeutic group: antihemorrhagics: blood coagulation factor VIII, ATC code B02BD02.

The factor VIII/von Willebrand factor (vWF) complex consists of two molecules (factor VIII andvWF) with different physiological functions. When infused into a haemophiliac patient, factor VIIIbinds to vWF in the patient’s circulation. Activated factor VIII acts as a cofactor for activatedfactor IX, accelerating the conversion of factor X to activated factor X. Activated factor X convertsprothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a clot can be formed.

Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels offactor VIII:C and results in profuse bleeding into joints, muscles or internal organs, eitherspontaneously or as a result of accidental or surgical trauma. By replacement therapy the plasma levelsof factor VIII are increased, thereby enabling a temporary correction of the factor deficiency andcorrection of the bleeding tendencies.

Of note, annualised bleeding rate (ABR) is not comparable between different factor concentrates andbetween different clinical studies.

Kovaltry does not contain von Willebrand factor.

The activated partial thromboplastin time (aPTT) is prolonged in people with haemophilia.

Determination of aPTT is a conventional in vitro assay for biological activity of factor VIII. Treatmentwith rFVIII normalizes the aPTT similar to that achieved with plasma-derived factor VIII.

Control and Prevention of Bleeding

Two multi-centre, open-label, cross-over, uncontrolled, randomised studies in previously treatedadults/adolescents with severe haemophilia A (< 1%) and one multi-centre, open-label, uncontrolledstudy in PTPs < 12 years of age (Part A) and PUPs/MTPs <6 years of age (Part B) with severehaemophilia A were conducted.

A total of 247 subjects (204 PTPs and 43 PUPs/MTPs) have been exposed in the clinical trial program,153 subjects ≥ 12 years and 94 subjects < 12 years. Two-hundred and eight (208) subjects (174 PTPs,34 PUPs/MTPs) were treated for at least 360 days, and 98 of these subjects (78 PTPs, 20 PUPs/MTPs)for at least 720 days.

Paediatric population <12 years

Part A: The paediatric trial enrolled 51 PTPs with severe haemophilia A, 26 subjects in the age group6-12 years and 25 subjects in the age group <6 years having accumulated a median number of 73 EDs(range: 37 to 103 EDs). Subjects were treated with 2 or 3 injections per week or up to every other day ata dose of 25 to 50 IU/kg. Consumption for prophylaxis and treatment of bleeds, annualised bleed ratesand success rate for bleed treatment are presented in Table 3.

Part B: A total of 43 PUPs/MTPs were enrolled and accumulated a median of 46 EDs(range 1 to 55 EDs). The median dose for treatment of bleeds in all PUPs/MTPs was 40.5 IU/kg and78.1% of the bleeds were successfully treated with ≤ 2 infusions.

The most frequently reported adverse reaction in PUPs/MTPs was Factor VIII inhibitor (seesection 4.8). FVIII inhibitors were detected in 23 of 42 patients with a median (range) of 9 (4 - 42)

EDs at the time of the first positive inhibitor test. Of these, 6 patients had low-titre inhibitors (≤ 5.0

BU) and 17 patients had high-titre inhibitors.

Extension: Of the 94 treated subjects, 82 subjects entered the Leopold Kids extension study,79 patients received treatment with Kovaltry and 67 patients received Kovaltry as prophylaxistreatment. The median time in the extension study was 3.1 years (range 0.3 to 6.4 years), the mediantotal time in entire study (main plus extension study) was 3.8 years (range 0.8 to 6.7 years).

During the extension study, 67 of 82 subjects received Kovaltry as prophylaxis treatment. Amongstthe 67 subjects, a total of 472 bleeds were treated with Kovaltry, requiring 1-2 infusions for themajority of bleeds (83.5%), and response to treatment was good or excellent in most (87.9%) of thecases.

Immune Tolerance Induction (ITI)

Data on ITI has been collected in patients with haemophilia A. 11 subjects with high titer inhibitorsreceived ITI with various treatment regimens of three times per week up to twice daily. 5 subjectscompleted ITI with a negative inhibitor result at the end of the study, and 1 subject had a low titer (1.2

BU/mL) at time of discontinuation.

Table 3: Consumption and overall success rates (patients treated with prophylaxis only)

Younger Older Adolescents and adults Totalchildren children 12-65 years(0 <6 (6 <12years) years)

Study 1 Study 2 Study 22 x/week 3 x/weekdosing dosing

Study 25 26 62 28 31 172participants

Dose/prophylaxis 36 IU/kg 32 IU/kg 31 IU/kg 30 IU/kg 37 IU/kg 32 IU/kginjection, IU/kg (21; (22; (21; (21; (30; (21;

BW 58 IU/kg) 50 IU/kg) 43 IU/kg) 34 IU/kg) 42 IU/kg) 58 IU/kg)median (min,max)

ABR - all bleeds 2.0 0.9 1.0 4.0 2.0 2.0(median, Q1,Q3) (0.0; 6.0) (0.0; 5.8) (0.0; 5.1) (0.0; 8.0) (0.0; 4.9) (0.0; 6.1)

Dose/injection 39 IU/kg 32 IU/kg 29 IU/kg 28 IU/kg 31 IU/kg 31 IU/kgfor bleed (21;72 IU/ (22; (13; (19; (21; (13;treatment kg) 50 IU/kg) 54 IU/kg) 39 IU/kg) 49 IU/kg) 72 IU/kg)

Median (min;max)

Success rate* 92.4% 86.7% 86.3% 95.0% 97.7% 91.4%

ABR annualised bleed rate

Q1 first quartile; Q3 third quartile

BW: Body weight

*Success rate defined as % of bleeds treated successfully with ≤ 2 infusions

The pharmacokinetic (PK) profile of Kovaltry was evaluated in PTPs with severe haemophilia Afollowing 50 IU/kg in 21 subjects ≥ 18 years, 5 subjects ≥ 12 years and < 18 years and 19 subjects< 12 years of age.

A population PK model was developed based on all available factor VIII measurements (from dense

PK sampling and all recovery samples) throughout the 3 clinical studies allowing calculation of PKparameters for subjects in the various studies. The table 4 below provides PK parameters based on thepopulation PK model.

Table 4: PK parameters (geometric mean (%CV)) based on chromogenic assay. *

PK parameter ≥ 18 years 12-<18 years 6-<12 years 0-<6 years

N=109 N=23 N=27 N=24

T1/2 (h) 14.8 (34) 13.3 (24) 14.1 (31) 13.3 (24)

AUC (IU.h/dL)** 1,858 (38) 1,523 (27) 1,242 (35) 970 (25)

CL (dL/h/kg) 0.03 (38) 0.03 (27) 0.04 (35) 0.05 (25)

Vss (dL/kg) 0.56 (14) 0.61 (14) 0.77 (15) 0.92 (11)

* Based on population PK estimates

**AUC calculated for a dose of 50 IU/kg

Repeated PK measurements after 6 to 12 months of prophylaxis treatment with Kovaltry did notindicate any relevant changes in PK characteristics after long-term treatment.

In an international study involving 41 clinical laboratories, the performance of Kovaltry in FVIII:Cassays was evaluated and compared to a marketed full length rFVIII product. Consistent results weredetermined for both products. The FVIII:C of Kovaltry can be measured in plasma with a one-stagecoagulation assay as well as with a chromogenic assay using the routine methods of the laboratory.

The analysis of all recorded incremental recoveries in previously treated patients demonstrated amedian rise of > 2% (> 2 IU/dL) per IU/kg body weight for Kovaltry. This result is similar to thereported values for factor VIII derived from human plasma. There was no relevant change over the6-12 months treatment period.

Table 5: Phase III incremental recovery results

Study participants N=115

Chromogenic assay results 2.3 (1.8; 2.6)

Median; (Q1; Q3) (IU/dL/IU/kg)

One-stage assay results 2.2 (1.8; 2.4)

Median; (Q1; Q3) (IU/dL/IU/kg)

Non-clinical data reveal no special risk for humans based on safety pharmacology, in vitrogenotoxicity, and short term repeat-dose toxicity studies. Repeat-dose toxicity studies longer than5 days, reproductive toxicity studies, and carcinogenicity studies, have not been performed. Suchstudies are not considered meaningful due to the production of antibodies against the heterologoushuman protein in animals. Also factor VIII is an intrinsic protein and not known to cause anyreproductive or carcinogenic effects.

Sucrose

Histidine

Glycine (E 640)

Sodium chloride

Calcium chloride dihydrate (E 509)

Polysorbate 80 (E 433)

Acetic acid, glacial (for pH adjustment) (E 260)

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

Only the provided infusion sets should be used for reconstitution and injection because treatmentfailure can occur as a consequence of human recombinant coagulation factor VIII adsorption to theinternal surfaces of some infusion equipment.

30 months

The chemical and physical in-use stability after reconstitution has been demonstrated for 3 hours atroom temperature.

After reconstitution, from a microbiological point of view, the product should be used immediately. Ifnot used immediately, in use storage times and conditions prior to use are the responsibility of theuser.

Do not refrigerate after reconstitution.

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Keep the vial and the pre filled syringe in the outer carton in order to protect from light.

Within its overall shelf life of 30 months the product when kept in its outer carton, may be stored up to25 °C for a limited period of 12 months. In this case, the product expires at the end of this 12 monthperiod or the expiry date on the product vial, whichever is earlier. The new expiry date must be notedon the outer carton.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

implantation

Each single package of Kovaltry contains:

* one vial with powder (10 mL clear glass type 1 vial with grey halogenobutyl rubber blendstopper and aluminium seal)

* one pre-filled syringe (3 mL or 5 mL) with 2.5 mL (for 250 IU, 500 IU and 1000 IU) or 5 mL(for 2000 IU and 3000 IU) solvent (clear glass cylinder type 1 with grey bromobutyl rubberblend stopper)

* syringe plunger rod

* vial adapter

* one venipuncture set

Pack sizes− 1 single pack.− 1 multipack with 30 single packs.

Not all pack sizes may be marketed.

Detailed instructions for preparation and administration are contained in the package leaflet providedwith Kovaltry.

The reconstituted medicinal product is a clear and colourless solution.

Kovaltry powder should only be reconstituted with the supplied solvent (2.5 mL or 5 mL water forinjections) in the prefilled syringe and the vial adapter. For infusion, the product must be preparedunder aseptic conditions. If any component of the package is opened or damaged, do not use thiscomponent.

After reconstitution the solution is clear. Parenteral medicinal products should be inspected visuallyfor particulate matter and discoloration prior to administration. Do not use Kovaltry if you noticevisible particulate matter or turbidity.

After reconstitution, the solution is drawn back into the syringe. Kovaltry should be reconstituted andadministered with the components (vial adapter, prefilled syringe, venipuncture set) provided witheach package.

The reconstituted product must be filtered prior to administration to remove potential particulatematter in the solution. Filtering is achieved by using the vial adapter.

The venipuncture set provided with the product must not be used for drawing blood because itcontains an in line filter.

For single use only.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Bayer AG51368 Leverkusen

Germany

EU/1/15/1076/002 1 x (Kovaltry 250 IU - solvent (2.5 mL); pre-filled syringe (3 mL))

EU/1/15/1076/012 - 1 x (Kovaltry 250 IU - solvent (2.5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/004 - 1 x (Kovaltry 500 IU - solvent (2.5 mL); pre-filled syringe (3 mL))

EU/1/15/1076/014 - 1 x (Kovaltry 500 IU - solvent (2.5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/006 - 1 x (Kovaltry 1000 IU - solvent (2.5 mL); pre-filled syringe (3 mL))

EU/1/15/1076/016 - 1 x (Kovaltry 1000 IU - solvent (2.5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/008 - 1 x (Kovaltry 2000 IU - solvent (5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/010 - 1 x (Kovaltry 3000 IU - solvent (5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/017 30 x (Kovaltry 250 IU - solvent (2.5 mL); pre-filled syringe (3 mL))

EU/1/15/1076/018 - 30 x (Kovaltry 250 IU - solvent (2.5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/019 - 30 x (Kovaltry 500 IU - solvent (2.5 mL); pre-filled syringe (3 mL))

EU/1/15/1076/020 - 30 x (Kovaltry 500 IU - solvent (2.5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/021 - 30 x (Kovaltry 1000 IU - solvent (2.5 mL); pre-filled syringe (3 mL))

EU/1/15/1076/022 - 30 x (Kovaltry 1000 IU - solvent (2.5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/023 - 30 x (Kovaltry 2000 IU - solvent (5 mL); pre-filled syringe (5 mL))

EU/1/15/1076/024 - 30 x (Kovaltry 3000 IU - solvent (5 mL); pre-filled syringe (5 mL))

Date of first authorisation: 18 February 2016

Date of latest renewal:

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.