Drug Safety-related Labeling Changes (SrLC)

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PRALUENT (BLA-125559)

(ALIROCUMAB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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11/06/2018 (SUPPL-18)

Approved Drug Label (PDF)

6 Adverse Reactions

Newly added subsection:

6.3 Postmarketing Experience

The following adverse reactions have been reported during postapproval use of PRALUENT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • General disorders and administration site conditions

    • Flu-like illness

07/20/2018 (SUPPL-15)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PRALUENT during pregnancy.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(addition underlined)

See FDA-Approved Patient Labeling (Patient Information and Instructions for Use).

Pregnancy Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PRALUENT during pregnancy. Encourage participation in the registry.

09/20/2017 (SUPPL-6)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

(subsection revised, additions underlined)

As with all therapeutic proteins, there is a potential for immunogenicity with PRALUENT. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to PRALUENT in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In a pool of ten placebo- and active-controlled trials, 4.8% (147/3033) of patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks (Q2W) had anti-drug antibodies (ADA) newly detected at least once after initiating treatment compared with 0.6% (10/1708) of patients treated with control. For 1.9% (57/3033) of patients treated with PRALUENT and 0.5% (8/1708) of patients treated with control, ADA were detected in at least 2 samples separated by at least 12 weeks or were detected only at the last sampling time point. Patients treated with PRALUENT 75 mg and/or 150 mg Q2W who ever developed ADA had a higher incidence of injection site reactions compared with patients who never had ADA detected (10.2% vs 5.9%).

In the same pool, 1.2% (36/3033) of patients treated with PRALUENT 75 mg and/or 150 mg Q2W had neutralizing antibodies (NAb) detected at least once, and 0.3% (9/3033) exhibited some attenuation in efficacy. No patients treated with control developed NAb. The long-term consequences of continuing PRALUENT treatment in the presence of persistent NAb are unknown.

In a separate clinical study of patients treated with PRALUENT 75 mg Q2W or 300 mg every 4 weeks (including some patients with dose adjustment to 150 mg Q2W), the incidence of detecting ADA and NAb was qualitatively similar to the results from the pooled trials described above.

04/24/2017 (SUPPL-1)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

… The safety of PRALUENT was evaluated in 9 placebo-controlled trials that included 2476 patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks, including 2135 exposed for 6 months and 1999 exposed for more than 1 year (median treatment duration of 65 weeks).

Following Table 1:

Local Injection Site Reactions

In a pool of placebo-controlled trials evaluating PRALUENT 75 mg and/or 150 mg administered every 2 weeks (Q2W), local injection site reactions including … and had reactions of longer average duration than patients receiving placebo.

Addition of the following:

In a 48-week placebo-controlled trial evaluating PRALUENT 300 mg every 4 weeks (Q4W) and 75 mg Q2W, in which all patients received an injection of drug or placebo every 2 weeks to maintain the blind, local injection site reactions were reported more frequently in patients treated with PRALUENT 300 mg Q4W as compared to those receiving PRALUENT 75 mg Q2W or placebo (16.6%, 9.6%, and 7.9%, respectively). Three patients (0.7%) treated with PRALUENT 300 mg Q4W discontinued treatment due to local injection site reactions versus no patients (0%) in the other 2 treatment groups.

Low LDL-C Values

Additions and/or revisions underlined:

In the placebo- and active-controlled clinical trials using an every 2 week or every 4 week dosing interval, 914 PRALUENT-treated patients had two consecutive calculated LDL-C values <25 mg/dL, and 335 had two consecutive calculated LDL-C values <15 mg/dL. LDL-C values < 25 mg/dL and <15 mg/dL were observed more frequently in patients treated with the PRALUENT 150 mg Q2W or 300 mg Q4W dosing regimens. Changes to background …

6.2 Immunogenicity

Additions and/or revisions underlined:

As with all therapeutic proteins, there is a potential for immunogenicity with PRALUENT. In a pool of ten placebo- and active-controlled trials, 4.8% of patients treated with PRALUENT 75 mg and/or 150 mg every 2 weeks (Q2W) exhibited anti-drug antibodies (ADA) newly detected after initiating treatment as compared with 0.6% of patients treated with control. In a separate study, 6.3% of patients treated with PRALUENT 75 mg Q2W or 300 mg every 4 weeks (Q4W) (including some patients with dose adjustment to 150 mg Q2W) exhibited a newly detected ADA versus 2.6% of patients treated with placebo.

In a pool of ten placebo- and active-controlled trials, patients treated with PRALUENT 75 mg and/or 150 mg Q2W who developed ADA had a higher incidence …

A total of 1.2% of patients treated with PRALUENT 75 mg and/or 150 mg Q2W developed neutralizing antibodies (NAb) … or prolonged loss of efficacy. In a separate study, 0.9% of patients treated with PRALUENT 75 mg Q2W or 300 mg Q4W (including some patients with dose adjustment to 150 mg Q2W) developed NAb on at least one occasion; no NAb were observed in patients treated with placebo. The long-term consequences …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

How should I use PRALUENT?

Additions and/or revisions underlined:

  • PRALUENT is injected under the skin (subcutaneously) every 2 weeks or every 4 weeks (monthly).

  • If your healthcare provider prescribes you the monthly dose, you will give yourself 2 separate injections in a row, using a different syringe or pen for each injection and two different injection sites.

  • If you forget to use PRALUENT or are not able to take the dose at your regular time, inject your missed dose as soon as you remember, within 7 days. Then, if you inject every 2 weeks take your next dose in 2 weeks from the day you missed your dose or if you inject every 4 weeks take your next dose in 4 weeks from the day you missed your dose. This will put you back on your original schedule.

  • If you missed a dose  by more than 7 days and you inject every 2 weeks wait until your next scheduled dose to re-start PRALUENT or if you inject every 4 weeks start a new schedule from the time you remember to take your dose.

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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