Sevenfact Drug Information

SEVENFACT is indicated for the treatment and control of bleeding episodes occurring in adults and adolescents 12 years of age and older with hemophilia A or B with inhibitors. Limitation s of Use: SEVENFACT is not indicated for the treatment of patients with congenital Factor VII deficiency.

Dose

For intravenous use after reconstitution only. Dose and duration of SEVENFACT depend on the location and severity of the bleeding, need for urgent hemostasis, frequency of administration, and known patient responsiveness to FVIIa-containing bypassing agents during prior bleeding events. Treatment with SEVENFACT should be initiated as soon as a bleeding event occurs.

The dose, frequency, and duration of SEVENFACT therapy should be based on the patient’s clinical response and hemostasis evaluation. The use of laboratory assessment(s) of coagulation (PT/INR, aPTT, FVII:C) does not necessarily correlate with or predict the hemostatic effectiveness of SEVENFACT. Dose adjustment may be required if the patient has received other procoagulant therapies prior to treatment with SEVENFACT.

Based on the clinical trial program for SEVENFACT, the recommended initial dose should be adjusted based on the criteria provided in Table 1. Table 1 Dosing for Treatment and Control of Bleeding

Reconstitution Follow the procedures below for reconstitution of SEVENFACT. Calculate the amount of SEVENFACT required and select the appropriate SEVENFACT packages containing the matching pre-filled syringe of sterile Water for Injection, and the vial adapters. Reconstitute each vial with the pre-filled syringe provided with each vial of SEVENFACT.

Overview of SEVENFACT P ackage: Figure 1 Vial with SEVENFACT L yophilized P owder Lyophilized Powder Drug Vial Figure 2 Syringe P lunger R od and P re-filled S yringe with Water for Injection D iluent Syringe Plunger Rod Pre-filled S yringe with Diluent Figure 3 SEVENFACT 1 mg and 2 mg V ial A dapter and SEVENFACT 5 mg V ial A dapter Vial Adapters* and Packaging 1 mg and 2 mg V ial A dapter 5 mg V ial A dapter N ote: Each SEVENFACT kit will contain only one vial adapter. The instructions below serve as a general guideline for reconstitution of SEVENFACT. Reconstitution: Based on the prescribed dose, take out the number of SEVENFACT kits (each kit containing one vial of SEVENFACT powder and one pre-filled Water for Injection diluent syringe with one vial adapter for needleless reconstitution), an infusion set (not supplied in the kit) and an alcohol swab (not supplied in the kit).

Check the expiration date on the side of the box(es) for the SEVENFACT kit(s). Always use aseptic technique. Wash your hands with soap and water and dry them using a clean towel or air dry.

Place items on a clean surface. Inspect all contents of the kit. Make sure each vial has a matching colored syringe.

Bring SEVENFACT (lyophilized powder) and the specified pre-filled syringe (diluent) to room temperature. The specified volume of diluent corresponding to the amount of SEVENFACT is as follows: 1 mg (1000 micrograms) vial + 1.1 mL Water for Injection diluent in pre-filled syringe 2 mg (2000 micrograms) vial + 2.2 mL Water for Injection diluent in pre-filled syringe 5 mg (5000 micrograms) vial + 5.2 mL Water for Injection diluent in pre-filled syringe Remove the plastic cap from the SEVENFACT vials to expose the central portion of the rubber stopper. Cleanse the rubber stoppers with an alcohol swab and allow to dry prior to use.

Peel back the protective paper from the vial adapter. Do not remove the vial adapter from the package. Place the SEVENFACT vial on a flat surface.

While holding the vial adapter package, place the vial adapter over the SEVENFACT vial and press down firmly on the package until the vial adapter spike breaks through the rubber stopper. Lightly squeeze the plastic cover and lift up to remove it from the vial adapter. Note: the 5 mg vial adapter may not sit flat against the vial, but it is fully functional.

Remove the syringe cap from the pre-filled syringe by holding the syringe body with one hand to unscrew the syringe cap (turn to the left). While holding the edges of the vial adapter, screw on the pre-filled syringe (turn to the right) a few turns until it starts to tighten. Insert the plunger rod into the syringe, then screw a few turns (turn to the right) so that the plunger rod is attached to the gray rubber stopper in the syringe.

Push the plunger rod to slowly inject all the diluent into the vial. Keep the plunger rod pressed down and swirl the vial gently until the powder is dissolved. The reconstituted solution is clear to slightly opaque.

All powder must be mixed with no particles floating in the liquid. Without withdrawing any drug back into the syringe, unscrew the syringe from the vial adapter (turn to the left) until it is completely detached. Withdraw the liquid drug from the vial(s), using an infusion syringe provided by the pharmacy; the syringe should be large enough to hold the prescribed dose.

After reconstitution with the specified volume of diluent, each vial contains approximately 1 mg per mL SEVENFACT (1000 micrograms per mL).

Administration For Intravenous Use Only

Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. Do not use if particulate matter or discoloration is observed. Do not freeze reconstituted solution or store it in a syringe.

SEVENFACT must be infused within 4 hours after reconstitution. SEVENFACT should be infused over 2 minutes or less as a bolus intravenous infusion. Do not mix with other infusion solutions.

Any unused solution should be discarded 4 hours after reconstitution.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety database described in this section reflect exposure to SEVENFACT in two clinical studies, Study 1 and Study 2. The most common adverse reactions (incidence ≥1%) reported in clinical trials for SEVENFACT were headache, dizziness, infusion-site discomfort, infusion-site hematoma, infusion-related reaction, and fever.

Adverse reactions reported in the two clinical studies are shown in Table 2. Table 2 Adverse Reactions Occurring in Clinical Studies 1 1 - - Three patients experienced adverse reactions in Study 2 and two patients experienced adverse reactions in Study 1. Symptoms resolved without any intervention and did not recur with subsequent administration.

Clinical experience with pharmacologic use of FVIIa-containing products indicates an elevated risk of serious thrombotic events when used simultaneously with activated prothrombin complex concentrates.

Pregnancy Risk Summary There are no adequate and well-controlled studies using SEVENFACT in pregnant women to determine whether there is a drug-associated risk. Animal studies evaluating the embryo-fetal teratogenic potential of SEVENFACT have not been conducted. It is unknown whether SEVENFACT can cause fetal harm when administered to a pregnant woman or can affect fertility.

In the U.S. general population, the estimated background risks of major birth defect and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Pediatric Use The safety and effectiveness of SEVENFACT have been established for pediatric patients ≥ 12 years of age for the treatment and control of bleeding episodes. Limited clinical data for SEVENFACT in adolescents (≥12 to <18 years) were collected in an adult and adolescent study (Study 1). A total of five patients were dosed with SEVENFACT.

These five patients were treated for a total of 79 bleeding episodes (all mild or moderate) that occurred while patients were still under 18 years of age. Hemostatic efficacy in this subgroup (n=5) was comparable to efficacy observed in the overall population. The safety and effectiveness of SEVENFACT for the treatment and control of bleeding episodes have not been established in children < 12 years of age.

Effectiveness was not demonstrated in a trial of 25 pediatric patients 6 months to < 12 years of age. The safety and effectiveness of SEVENFACT in infants less than 6 months of age have not been evaluated.

SEVENFACT is contraindicated in patients with: known allergy to rabbits or rabbit proteins. Exposure to SEVENFACT in these patients can result in severe hypersensitivity reaction. severe hypersensitivity reaction to SEVENFACT or any of its components. Known allergy to rabbits or rabbit proteins.