BERINERT

1 Dosing Considerations • BERINERT should not be mixed with other medicinal products and should be administered by a separate infusion line. • If self-administration is considered, ensure that the patient receives instructions and training on intravenous administration.

• For patients that are traveling, advise patients to bring an adequate supply of BERINERT for their treatments. 2 Recommended Dose and Dosage Adjustment The recommended dose of BERINERT in the treatment of abdominal, facial and laryngeal HAE attacks of moderate to severe intensity is 20 IU per kg body weight administered by intravenous injection.

3 Reconstitution Table 1 – Reconstitution Format Vial Size Volume of Diluent to be Added to Vial Approximate Available Volume Concentration per mL 500 17 mL 10 mL 10 mL 50 IU/mL 1500 10 mL 3 mL 3 mL 500 IU/mL BERINERT 500 should be reconstituted with the provided 10 mL of Sterile Water for Injection (Diluent).

BERINERT 1500 should be reconstituted with the provided 3 mL of Sterile Water for Injection (Diluent). Use the Mix2Vial® filter transfer set provided with BERINERT (see

1 Adverse Reaction Overview The most serious adverse reaction reported in subjects in clinical studies who received BERINERT is an increase in the severity of pain associated with HAE. The most common adverse reactions that have been reported in greater than 4% of the subjects who received BERINERT are HAE, headache, dysgeusia, abdominal pain, nausea, muscle spasms, pain, diarrhea, and vomiting.

BERINERT® 500 / BERINERT® 1500, C1 Esterase Inhibitor, Human Page 11 of 42 The other common adverse reactions that have been reported in 1% to 4 % of the subjects who received BERINERT are back pain, edema peripheral, abdominal distension and upper respiratory tract infection, including nasopharyngitis.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Placebo-Controlled Pivotal Study In a pivotal Phase III clinical study, 124 subjects experiencing an acute moderate to severe abdominal or facial HAE attack were treated with BERINERT (either a 10 IU per kg body weight dose, 20 IU per kg body weight dose), or placebo (physiological saline solution).

Table 3, Table 4, and Table 5 list the associated Adverse Events (AEs) that occurred in more than 4% of the subjects up to 4 hours, 72 hours and 9 days respectively after the end of a BERINERT infusion, irrespective of causality. , adverse reactions).

† The following abdominal symptoms were identified in the protocol as associated with HAE abdominal attacks: abdominal pain, bloating, cramps, nausea, vomiting, and diarrhea. , adverse reactions). † If a subject experienced no relief or insufficient relief of symptoms within 4 hours after infusion, investigators had the option to administer a blinded second infusion (“rescue” treatment) of BERINERT (20 IU/kg for the placebo group or 10 IU/kg for the 10 IU/kg group), or placebo (for the 20 IU/kg group).

Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX. This product is prepared from large pools of human plasma. Thus, there is a possibility it may contain causative agents of viral or other undetermined diseases. General BERINERT is made from human plasma and may contain pathogens such as viruses and, theoretically, the agent responsible for the Creutzfeldt-Jakob disease (CJD).

The risk that such products will transmit an infectious agent has been reduced by implementing stringent measures to reduce the risk of contamination by pathogens (for more information please see 13 PHARMACEUTICAL INFORMATION, subsection Viral Inactivation).

The current manufacturing process includes multiple steps that reduce the risk of viral transmission. Since February 22, 2001 (date of licensure of the current product formulation), no proven case of virus transmission has been attributed to BERINERT.

The manufacturing process of the BERINERT drug substance up to and including the virus filtration step is identical for BERINERT 500 and BERINERT 1500. Despite these measures, human plasma-derived products may still potentially transmit diseases.

There is also the possibility that unknown infectious agents may be present in such products. All infections thought by a physician to have been possibly transmitted by this product should be reported by the latter or another healthcare provider to CSL Behring at 1-866-773-7721.

The physician or healthcare provider should discuss the risks and benefits of this product with the patient. Cardiovascular Thrombotic events have been reported at the recommended dose of C1 Esterase Inhibitor (Human) products, including BERINERT, following treatment of HAE attacks.

Thrombotic events also have been reported when used off-label and at higher than labeled doses. Patients with known risk factors for thrombotic events should be monitored closely. BERINERT® 500 / BERINERT® 1500, C1 Esterase Inhibitor, Human Page 10 of 42 Sensitivity/Resistance As with any pharmaceutical agent, allergic reactions may occur.

• BERINERT is contraindicated in individuals who have a known hypersensitivity or have had an anaphylactic or severe systemic reaction to C1-INH preparations or to any ingredient in the formulation or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.