PALFORZIA can cause anaphylaxis, which may be life-threatening.

Anaphylaxis has been reported during all phases of PALFORZIA dosing, including Maintenance and in subjects who have undergone recommended Up-Dosing and dose modification procedures.

In 709 PALFORZIA-treated subjects and 292 placebo-treated subjects in the placebo-controlled population in Studies 1 and 2 combined [see Adverse Reactions (6.1)] , anaphylaxis was reported in 9.4% of PALFORZIA-treated subjects compared with 3.8% of placebo-treated subjects during Initial Dose Escalation and Up-Dosing combined, and in 8.7% of PALFORZIA-treated subjects compared with 1.7% of placebo-treated subjects during Maintenance in Study 1. Epinephrine use for any reason was reported in 10.4% of PALFORZIA-treated subjects compared with 4.8% of placebo-treated subjects during Initial Dose Escalation and Up-Dosing combined, and in 7.7% of PALFORZIA-treated subjects compared with 3.4% of placebo-treated subjects during Maintenance dosing in Study 1. Time to onset of anaphylaxis occurred within 2 hours after dosing in 70% of reactions, greater than 2 hours and up to 10 hours in 18% of reactions, and greater than 10 hours in 12% of reactions among PALFORZIA-treated subjects. 

Do not initiate PALFORZIA treatment in a patient who has had severe or life-threatening anaphylaxis within the previous 60 days. PALFORZIA may not be suitable for patients with certain medical conditions that may reduce the ability to survive anaphylaxis, including but not limited to markedly compromised lung function, severe mast cell disorder, or cardiovascular disease. In addition, PALFORZIA may not be suitable for patients taking medications that can inhibit or potentiate the effects of epinephrine.

All Initial Dose Escalation doses and the first dose of each Up-Dosing level must be administered under observation in a health care setting [see Dosage and Administration (2.5)] . Prior to initiating PALFORZIA treatment, educate patients to recognize the signs and symptoms of anaphylaxis. Prescribe injectable epinephrine, instruct and train patients on its appropriate use, and instruct patients to seek immediate medical care upon its use. Instruct patients to contact their health care professional before administering the next dose of PALFORZIA if anaphylaxis or symptoms of an escalating or persistent allergic reaction occur as dose modification may be necessary [see Dosage and Administration (2.4)] . 

Patients may be more likely to experience allergic reactions following PALFORZIA administration in the presence of cofactors such as exercise, hot water exposure, intercurrent illness (e.g., viral infection), or fasting. Other potential cofactors may include menstruation, sleep deprivation, nonsteroidal anti-inflammatory drug use, or uncontrolled asthma. Patients should be proactively counseled about the potential for the increased risk of anaphylaxis in the presence of these cofactors. If possible, adjust the time of dosing to avoid these cofactors. If it is not possible to avoid these cofactors, consider withholding PALFORZIA temporarily.

If appropriate to re-start administering PALFORZIA in patients who experienced anaphylaxis while on PALFORZIA or who had doses withheld to avoid increased risk of anaphylaxis, consider a dose reduction and dose re-escalation based on clinical judgment [see Dosage and Administration (2.5)] . 

PALFORZIA is available only through a restricted program under a REMS [see Warnings and Precautions (5.2)] .