Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

ABILIFY MAINTENA KIT (NDA-202971)

(ARIPIPRAZOLE)

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

Download Data

Expand all

02/05/2020 (SUPPL-13)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post-approval use of oral aripiprazole or ABILIFY MAINTENA. 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: occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups, blood glucose fluctuation, and drug reaction with eosinophilia and systemic symptoms (DRESS).

07/27/2017 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Metabolic Changes

(additions underlined)

Hyperglycemia/Diabetes Mellitus

…

During a 52-week, open-label bipolar I disorder study in those patients who initiated ABILIFY MAINTENA treatment, 1.1% with normal baseline fasting glucose experienced a shift to high while receiving ABILIFY MAINTENA and 9.8% with borderline fasting glucose experienced a shift to high. Combined, 2.9% of these patients with normal or borderline fasting glucose experienced shifts to high fasting glucose during this trial.

Dyslipidemia

…

During a 52-week, open-label bipolar I disorder study in those patients who initiated ABILIFY MAINTENA, shifts from baseline in fasting cholesterol from normal to high were reported in 2.1% (total cholesterol) and 2.2% (LDL cholesterol) and shifts from baseline from normal to low were reported in 8.5% (HDL cholesterol). Of these patients with normal baseline triglycerides, 3.6% experienced shifts to high, and 0.0% experienced shifts to very high. Combined, 1.0% of these patients with normal or borderline fasting triglycerides experienced shifts to very high fasting triglycerides during this trial.

Weight Gain

Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

In one short-term, placebo-controlled trial in adult patients with schizophrenia with ABILIFY MAINTENA, the mean change in body weight at Week 12 was +3.5 kg (N=99) in the ABILIFY MAINTENA-treated patients and +0.8 kg (N=66) in the placebo-treated patients.

Table 6 shows the percentage of adult patients with schizophrenia with weight gain ?7% of body weight in a short-term, placebo-controlled trial with ABILIFY MAINTENA.

(please refer to label to view Table 6)

During a 52-week, open-label bipolar I disorder study in those patients who initiated ABILIFY MAINTENA, 1.8% discontinued ABILIFY MAINTENA treatment due to weight increase. ABILIFY MAINTENA was associated with mean increase from baseline in weight of 1.0 kg at week 52. In this trial, 21.4% of these patients demonstrated equal to or greater than 7% increase in body weight and 15.4% demonstrated an equal to or greater than 7% decrease in body weight.

5.7 Orthostatic Hypotension

(additions underlined)

ABILIFY MAINTENA may cause orthostatic hypotension, perhaps due to its ?1- adrenergic receptor antagonism. In the short-term, placebo-controlled trial in adults with schizophrenia, the adverse event of presyncope was reported in 1/167 (0.6%) of patients treated with ABILIFY MAINTENA, while syncope and orthostatic hypotension were each reported in 1/172 (0.6%) of patients treated with placebo. During the stabilization phase of the randomized-withdrawal (maintenance) study in adult patients with schizophrenia, orthostasis-related adverse events were reported in 4/576 (0.7%) of patients treated with ABILIFY MAINTENA, including abnormal orthostatic blood pressure (1/576, 0.2%), postural dizziness (1/576, 0.2%), presyncope (1/576, 0.2%) and orthostatic hypotension (1/576, 0.2%).

In the short-term placebo-controlled trial in adults with schizophrenia, there were no patients in either treatment group with a significant orthostatic change in blood pressure (defined as a decrease in systolic blood pressure ?20 mmHg accompanied by an increase in heart rate ?25 bpm when comparing standing to supine values). During the stabilization phase of the randomized-withdrawal (maintenance) study in adult patients with schizophrenia, the incidence of significant orthostatic change in blood pressure was 0.2% (1/575).

6 Adverse Reactions

6.1 Clinical Trials Experience

(additions underlined)

…

Safety Database of ABILIFY MAINTENA and Oral Aripiprazole

Oral aripiprazole has been evaluated for safety in 16,114 adult patients who participated in multiple-dose, clinical trials in schizophrenia and other indications, and who had approximately 8,578 patient-years of exposure to oral aripiprazole. A total of 3,901 patients were treated with oral aripiprazole for at least 180 days, 2,259 patients were treated with oral aripiprazole for at least 360 days, and 933 patients continuing aripiprazole treatment for at least 720 days.

ABILIFY MAINTENA has been evaluated for safety in 2,128 adult patients in clinical trials in schizophrenia, with approximately 2,633 patient-years of exposure to ABILIFY MAINTENA. A total of 1,229 patients were treated with ABILIFY MAINTENA for at least 180 days (at least 7 consecutive injections) and 935 patients treated with ABILIFY MAINTENA had at least 1 year of exposure (at least 13 consecutive injections).

ABILIFY MAINTENA has been evaluated for safety in 804 adult patients in clinical trials in bipolar I disorder, with approximately 530 patient-years of exposure to ABILIFY MAINTENA. A total of 419 patients were treated with ABILIFY MAINTENA for at least 180 days (at least 7 consecutive injections) and 287 patients treated with ABILIFY MAINTENA had at least 1 year of exposure (at least 13 consecutive injections).

The conditions and duration of treatment with ABILIFY MAINTENA included double- blind and open-label studies. The safety data presented below are derived from the 12- week double-blind placebo-controlled study of ABILIFY MAINTENA in adult patients with schizophrenia.

Adverse Reactions with ABILIFY MAINTENA

…

Musculoskeletal and Connective Tissue Disorders: infrequent - joint stiffness, muscle twitching, trismus; rare – rhabdomyolysis

…

Reproductive System and Breast Disorders: infrequent- ejaculation delayed

…

02/23/2017 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Falls

(Newly added subsection)

Antipsychotics, including ABILIFY MAINTENA, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following adverse reactions are discussed in more detail in other sections of the labeling:

Falls

08/18/2016 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

Pathological Gambling and Other Compulsive Behaviors

Post-marketing case reports suggest that patients can experience intense urges, particularly for gambling, and the inability to control these urges while taking aripiprazole. Other compulsive urges, reported less frequently include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or intense gambling urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or other urges while being treated with aripiprazole. It should be noted that impulse-control symptoms can be associated with the underlying disorder. In some cases, although not all, urges were reported to have stopped when the dose was reduced or the medication was discontinued. Compulsive behaviors may result in harm to the patient and others if not recognized. Consider dose reduction or stopping the medication if a patient develops such urges.

6 Adverse Reactions

The following adverse reactions are discussed in more detail in other sections of the labeling:

Pathological Gambling and Other Compulsive Behaviors (addition)

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

MG - What are the possible side effects of ABILIFY MAINTENA?

ABILIFY MAINTENA may cause serious side effects, including:

Unusual urges. Some people taking ABILIFY have had unusual urges, such as gambling, binge eating or eating that you cannot control (compulsive), compulsive shopping and sexual urges.

If you or your family members notice that you are having unusual urges or behaviors, talk to your healthcare provider.

PCI - Discuss the following issues with patients prescribed ABILIFY MAINTENA:

Pathological Gambling and Other Compulsive Behaviors

Advise patients and their caregivers of the possibility that they may experience compulsive urges to shop, intense urges to gamble, compulsive sexual urges, binge eating and/or other compulsive urges and the inability to control these urges while taking aripiprazole. In some cases, but not all, the urges were reported to have stopped when the dose was reduced or stopped.

01/15/2016 (SUPPL-8)

Approved Drug Label (PDF)

6 Adverse Reactions

Postmarketing Experience

addition of pathological gambling and hiccups