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.

QSYMIA (NDA-022580)

(PHENTERMINE HYDROCHLORIDE; TOPIRAMATE)

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

Download Data

Expand all

03/06/2026 (SUPPL-31)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

QSYMIA is contraindicated in patients:

. . .

With known hypersensitivity to phentermine, topiramate or any of the excipients in QSYMIA, or idiosyncrasy to the sympathomimetic amines. Anaphylaxis and angioedema have occurred with topiramate [see Warnings and Precautions (5.15)].

5 Warnings and Precautions

5.13 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions

Newly added subsection

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity has been reported in patients taking topiramate. DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. QSYMIA should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

5.15 Anaphylaxis and Angioedema

Newly added subsection

Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients treated with topiramate in the postmarketing setting. If a hypersensitivity reaction occurs, discontinue QSYMIA and initiate appropriate therapy [see Contraindications (4)].

6 Adverse Reactions

Additions and/or revisions underlined:

The following clinically significant adverse reactions are described elsewhere in the labeling:

. . .

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions (5.13)]
Serious Skin Reactions [see Warnings and Precautions (5.14)]
Anaphylaxis and Angioedema [see Warnings and Precautions (5.15)]
Allergic Reactions Due to Inactive Ingredients FD&C Yellow No. 5 [see Warnings and Precautions (5.16)]

6.2 Postmarketing Experience

Additions and/or revisions underlined:

. . .

Topiramate

Hypersensitivity: immediate hypersensitivity reactions (including anaphylaxis and angioedema, delayed hypersensitivity reactions (including facial swelling, lip swelling, periorbital swelling, tongue swelling) anaphylaxis, angioedema, facial swelling, lip swelling, tongue swelling, periorbital edema

Dermatologic: bullous skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), pemphigus, urticaria

. . .

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

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

Before taking QSYMIA, tell your health care provider about all of your medical conditions, including if you:

. . .

are allergic to FD&C Yellow No. 5 (tartrazine)

. . .

What are the possible side effects of QSYMIA? QSYMIA can cause serious side effects, including:

. . .

Severe multiorgan reactions. Treatment with QSYMIA may cause a serious allergic reaction that may affect your skin or other parts of your body such as your liver, kidneys, heart, or blood cells. This allergic reaction can be life threatening and can cause death, particularly if it is not treated as early as possible. Contact your healthcare provider or get medical help right away if you have:

blistering and peeling of your skin or skin rash
fever or swollen glands that do not go away
hives
swelling of your face, eyes, lips, tongue, or throat
sores in your mouth
trouble swallowing or breathing
dark urine
yellowing of the skin or whites of the eyes

. . .

Allergic reactions.

Serious allergic reactions can happen after you take QSYMIA. Get emergency help right away if you have swelling of the face, lips, eyes, tongue, or throat, or trouble swallowing or breathing.

. . .

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions

Instruct patients that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related. Advise patients to report such reactions to a healthcare provider immediately [see Warnings and Precautions (5.13)].

Serious Skin Reactions

Inform patients about the signs of serious skin reactions. Instruct patients to immediately inform their healthcare provider at the first appearance of skin rash [see Warnings and Precautions (5.14)].

Anaphylaxis and Angioedema

Inform patients about the signs and symptoms of hypersensitivity reactions such as anaphylaxis and angioedema, which can occur with QSYMIA. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.15)].

. . .

09/13/2024 (SUPPL-25)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and revisions underlined:

…

Increase in Heart Rate

In adult and pediatric clinical trials, there was a higher incidence of heart rate elevations observed in QSYMIA- treated compared to placebo-treated patients. In an 8-week ambulatory blood pressure monitoring (ABPM) study in adults, QSYMIA increased the 24-hr average heart rate by 3.6 beats per minute (bpm) (95% CI 2.1, 5.2) compared to the placebo group [see Clinical Pharmacology (12.2)].

In clinical trials, a higher percentage of QSYMIA-treated adults and pediatric patients aged 12 years and older experienced heart rate increases from baseline of more than 5, 10, 15, and 20 bpm compared to placebo-treated patients. Table 3 and Table 4 provide the numbers and percentages of adult and pediatric patients, respectively, with elevations in heart rate in clinical studies of up to one year.

Please refer to label to view Table 3 and Table 4.

…

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of QSYMIA as an adjunct to a reduced-calorie diet and increased physical activity for weight reduction and long-term maintenance of body weight have been established in pediatric patients aged 12 years and older with obesity. Use of QSYMIA for this indication is supported by a 56-week, double-blind, placebo-controlled study in 223 pediatric patients aged 12 years and above, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

…

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

MEDICATION GUIDE

Additions and/or revisions for consistency with the Prescribing Information; please refer to label for complete information.

06/28/2023 (SUPPL-23)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Embryo-Fetal Toxicity

Additions and/or revisions underlined

QSYMIA can cause fetal harm. Data from pregnancy registries and epidemiologic studies indicate that a fetus exposed to topiramate in the first trimester of pregnancy has an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (SGA). When multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring. A negative pregnancy test is recommended before initiating QSYMIA treatment in patients who can become pregnant and monthly during QSYMIA therapy. Advise patients who can become pregnant of the potential risk to a fetus and to use effective contraception during QSYMIA therapy [see Use in Specific Populations (8.1,8.3)].

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

QSYMIA is contraindicated in pregnant patients. The use of QSYMIA can cause fetal harm, and weight loss offers no clear clinical benefit to a pregnant patient (see Clinical Considerations). Available data from pregnancy registries and epidemiologic studies indicate an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being SGA in infants exposed in utero to topiramate (see Data). When phentermine and topiramate were co-administered to rats at doses of 3.75 and 25 mg/kg, respectively [approximately 2 times the maximum recommended human dose (MRHD) based on area under the curve (AUC)], or at the same dose to rabbits (approximately 0.1 times and 1 time, respectively, the clinical exposures at the MRHD based on AUC), there were no drug-related malformations. However, structural malformations, including craniofacial defects and reduced fetal weights occurred in offspring of multiple species of pregnant animals administered topiramate at clinically relevant doses (see Data). Advise pregnant women of the potential risk to a fetus.

…

Data

Human Data

…

Major Congenital Malformations

The NAAED Pregnancy Registry indicates an increased risk of major congenital malformations, including but not limited to oral clefts in infants exposed to topiramate during the first trimester of pregnancy. Other than oral clefts, no specific pattern of major congenital malformations or grouping of major congenital malformation types were observed. In the NAAED pregnancy registry, when topiramate-exposed infants with only oral clefts were excluded, the prevalence of major congenital malformations (4.1%) was higher than that in infants exposed to a reference antiepileptic drug (AED) (1.8%) or in infants with mothers without epilepsy and without exposure to AEDs (1.1%).

Oral Clefts

In the NAAED Pregnancy Registry, the prevalence of oral clefts among topiramate-exposed infants (1.4%) was higher than the prevalence in infants exposed to a reference AED (0.3%) or the prevalence in infants with mothers without epilepsy and without exposure to AEDs (0.11%). It was also higher than the background prevalence in United States (0.17%) as estimated by the Centers for Disease Control and Prevention (CDC).

The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 12.5 (95% Confidence Interval [CI] 5.9-26.37) as compared to the risk in a background population of untreated women. The UK Epilepsy and Pregnancy Register reported a prevalence of oral clefts among infants exposed to topiramate monotherapy (3.2%) that was 16 times higher than the background rate in the UK (0.2%).

…

Small for Gestational Age

Data from the NAAED Pregnancy Registry and population-based birth registry cohort indicate that exposure to topiramate in utero is associated with an increased risk of SGA newborns (birth weight <10th percentile). In the NAAED Pregnancy Registry, 19.7% of topiramate-exposed newborns were SGA compared to 7.9% of newborns exposed to a reference AED and 5.4% of newborns of mothers without epilepsy and without AED exposure. In the medical Birth Registry of Norway, a population-based pregnancy registry, 25% of newborns in the topiramate monotherapy exposure group were SGA compared to 9% in the comparison group unexposed to AEDs. The long-term consequences of the SGA findings are not known.

…

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Ophthalmologic Adverse Reactions

Inform patients that QSYMIA can increase the risk of acute myopia, secondary angle closure glaucoma, and visual field defects. Advise patients to immediately report symptoms of severe and persistent eye pain or significant changes in their vision to their healthcare provider(s) [see Warnings and Precautions (5.4)].

…

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about QSYMIA? QSYMIA can cause serious side effects, including:

Birth defects. If you take QSYMIA during pregnancy, your baby has a higher risk for birth defects including cleft lip and cleft palate. Your baby may also be smaller than expected at birth. The long-term effects of this are not known. These defects can begin early in pregnancy, even before you know you are pregnant.
…
Do not stop QYSMIA without first talking to a healthcare provider.

Stopping QYSMIA suddenly can cause serious problems.
Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?
Pay attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings.
Keep all follow-up visits with your healthcare provider as scheduled.
Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Before taking QSYMIA, tell your healthcare provider about all of your medical conditions, including if you:
…

have a history of too much acid in the blood (metabolic acidosis) or a condition that puts you at higher risk for metabolic acidosis such as
- chronic diarrhea, surgery, a diet high in fat and low in carbohydrates (ketogenic diet), weak, brittle, or soft bones (osteoporosis, osteomalacia (rickets), osteopenia), or decreased bone density.
  …
  How should I take QSYMIA?

Your healthcare provider should start you on a diet and exercise program when you start taking QSYMIA. Stay on this program while you are taking QSYMIA.
Take QSYMIA exactly as your healthcare provider tells you to take it.
Do not change your dose without talking to your healthcare provider.
Take QSYMIA daily in the morning.
…
What are the possible side effects of QSYMIA?
QSYMIA can cause serious side effects, including:
…

Low potassium. QSYMIA can increase your risk of low potassium levels. Your healthcare provider should do a blood test to measure the level of potassium in your blood before and during treatment with QSYMIA.
…
How should I store QSYMIA?

Store QSYMIA at room temperature between 68°F to 77°F (20°C to 25°C).
Keep QSYMIA in a tightly closed container.
Keep QSYMIA dry and away from moisture.
…

06/24/2022 (SUPPL-21)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined

…

Taking or within 14 days of stopping a monoamine oxidase inhibitors [see Drug Interactions (7)]
With known hypersensitivity to phentermine, topiramate or other component of QSYMIA, or idiosyncrasy to the sympathomimetic amines [see Adverse Reactions (6.2)].

5 Warnings and Precautions

5.10 Risk of Hypoglycemia in Patients with Type 2 Diabetes Mellitus on Antidiabetic Therapy

Additions and/or revisions underlined

Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (e.g., sulfonylureas). QSYMIA has not been studied in combination with insulin. Measure blood glucose levels prior to starting QSYMIA and during QSYMIA treatment in patients with type 2 diabetes on antidiabetic medication. The risk of hypoglycemia may be lowered by a reduction of the dosage of insulin and/or insulin secretagogues. If a patient develops hypoglycemia after starting QSYMIA, appropriate changes should be made to the antidiabetic drug regimen.

5.13 Kidney Stones

Additions and/or revisions underlined

QSYMIA has been associated with kidney stone formation [see Adverse Reactions (6.1)]. Topiramate inhibits carbonic anhydrase activity and promotes kidney stone formation by reducing urinary citrate excretion and increasing urine pH. Patients on a ketogenic diet may be at increased risk for kidney stone formation. An increase in urinary calcium and a marked decrease in urinary citrate was observed in topiramate-treated pediatric patients in a one-year, active-controlled study. Increased ratio of urinary calcium/citrate increases the risk of kidney stones and/or nephrocalcinosis.

…

5.14 Oligohidrosis and Hyperthermia

Additions and/or revisions underlined

…

The majority of the reports associated with topiramate have been in pediatric patients. Advise all patients and caregivers to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather. Patients on concomitant medications that predispose them to heat-related disorders may be at increased risk.

5.15 Hypokalemia

Additions and/or revisions underlined

QSYMIA can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity. In addition, when QSYMIA is used in conjunction with non-potassium sparing diuretics this may further potentiate potassium-wasting. Measure potassium before and during treatment with QSYMIA. [see Adverse Reactions (6.1), Drug Interactions (7), and Clinical Pharmacology (12.3)].

5.16 Serious Skin Reactions

Newly added subsection

Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) have been reported in patients receiving topiramate. QSYMIA should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. Inform patients about the signs of serious skin reactions.

5.17 Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5

Newly added subsection

This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

5.2 Increase in Heart Rate

Additions and/or revisions underlined

QSYMIA can cause an increase in resting heart rate. A higher percentage of QSYMIA-treated adults and pediatric patients aged 12 years and older experienced heart rate increases from baseline of more than 5, 10, 15, and 20 beats per minute (bpm) compared to placebo-treated patients [see Adverse Reactions (6.1)]. The clinical significance of a heart rate elevation with QSYMIA treatment is unclear, especially for patients with cardiac and cerebrovascular disease.

…

5.3 Suicidal Behavior and Ideation

Additions and or revisions underlined

…

In a QSYMIA clinical trial of pediatric patients aged 12 years and older, 1 (0.6%) of the 167 QSYMIA-treated patients reported suicidal ideation and behavior which required hospitalization. No placebo-treated patients reported suicidal behavior or ideation.

…

5.4 Risk of Ophthalmologic Adverse Reactions

Additions and /or revisions underlined

Acute Myopia and Secondary Angle Closure Glaucoma

A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients treated with topiramate. Symptoms include acute onset of decreased visual acuity and/or ocular pain.

Ophthalmologic findings can include myopia, mydriasis, anterior chamber shallowing, ocular hyperemia (redness), choroidal detachments, retinal pigment epithelial detachments, macular striae, and increased intraocular pressure. This syndrome may be associated with supraciliary effusion resulting in anteriordisplacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within 1 month of initiating treatment with topiramate but may occur at any time during therapy. In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with topiramate has been reported in pediatric patients as well as adults. The primary treatment to reverse symptoms is discontinuation of QSYMIA as rapidly as possible [see Warnings and Precautions (5.12)]. Elevated intraocular pressure of any etiology, if left untreated, can lead to serious adverse reactions including permanent loss of vision.

Visual Field Defects

Visual field defects (independent of elevated intraocular pressure) have been reported in clinical trials and in postmarketing experience in patients receiving topiramate. In clinical trials, most of these events were reversible after topiramate discontinuation. If visual problems occur at any time during treatment, consider discontinuing QSYMIA.

5.6 Cognitive Impairment

Additions and/or revesions underlined

QSYMIA can cause cognitive dysfunction (e.g., impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties). Rapid titration or high initial doses of QSYMIA may be associated with higher rates of cognitive events such as attention, memory, and language/word-finding difficulties [see Adverse Reactions (6.1)]. The concomitant use of alcohol or central nervous system (CNS) depressant drugs with QSYMIA may potentiate CNS depression or other centrally mediated effects of these agents, such as dizziness, cognitive adverse reactions, drowsiness, light- headedness, impaired coordination, and somnolence.

Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain QSYMIA therapy does not affect them adversely. Caution patients against excessive alcohol intake while receiving QSYMIA.

If cognitive dysfunction persists, consider dosage reduction or discontinuation of QSYMIA [see Warnings and Precautions (5.12)].

5.7 Slowing of Linear Growth

Newly added subsection

QSYMIA is associated with a reduction in height velocity (centimeters of height gained per year) in obese pediatric patients 12 to 17 years of age. In a 56-week study, average height increased from baseline in both QSYMIA- and placebo-treated patients; however, a lower height velocity of -1.3 to -1.4 cm/year was observed in QSYMIA-treated compared to placebo-treated patients. Monitor height velocity in pediatric patients treated with QSYMIA. Consider dosage reduction or discontinuation of QSYMIA if pediatric patients are not growing or gaining height as expected [see Warnings and Precautions (5.12)].

5.8 Metabolic Acidosis

Additions and/or revisions underlined

…

Chronic metabolic acidosis in pediatric patients may also reduce growth rates, which may decrease the maximal height achieved.

…

Measure electrolytes including serum bicarbonate prior to starting QSYMIA and during QSYMIA treatment. In QSYMIA clinical trials, the peak reduction in serum bicarbonate typically occurred within 4 weeks of titration to the assigned dose, and in most patients there was a correction of bicarbonate by week 56, without any dosage reduction. However, if persistent metabolic acidosis develops while taking QSYMIA, reduce the dosage or discontinue QSYMIA [see Warnings and Precautions (5.12)].

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Slowing of Linear Growth [see Warnings and Precautions (5.7)]
Decrease in Renal Function [see Warnings and Precautions (5.9)]
Risk of Seizures with Abrupt Withdrawal of QSYMIA [see Warnings and Precautions (5.12)]
Kidney Stones [see Warnings and Precautions (5.13)]
Oligohydrosis and Hyperthermia [see Warnings and Precautions (5.14)]
Hypokalemia [see Warnings and Precautions (5.15)]
Serious Skin Reactions [see Warnings and Precautions (5.16)]

6.1 Clinical Trials Experience

Extensive additions and/or revisions, please refer to label for complete information.

6.2 Postmarketing Experience

Additions and/or revisions underlined

…

Topiramate

…

Metabolic: hyperammonemia with or without encephalopathy has been reported with concomitant valproic acid [see Drug Interactions (7)], hypothermia

…

7 Drug Interactions

Addition of the following information to Table 7:

Amitriptyline

Clinical Impact: Some patients may experience a large increase in amitriptyline concentration in the presence of topiramate.

Intervention: Any adjustments in amitriptyline dose when used with QSYMIA should be made according to the patient's clinical response and not on the basis of amitriptyline levels [see Clinical Pharmacology (12.3)].

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined

The safety and effectiveness of QSYMIA as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in pediatric patients aged 12 years and older with a BMI in the 95th percentile or greater standardized for age and sex have been established. Use of QSYMIA for this indication is supported by a 56-week, double-blind, placebo-controlled study in 223 pediatric patients aged 12 years and above, a pharmacokinetic study in pediatric patients, and studies in adults with obesity [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

In a pediatric clinical trial, there was one episode of serious suicidal ideation in a QSYMIA-treated patient requiring hospitalization and pharmacologic treatment [see Warnings and Precautions (5.3)]; more patients treated with QSYMIA versus placebo reported adverse reactions related to mood (e.g., depression, anxiety) and sleep disorders (e.g., insomnia) [see Warnings and Precautions (5.5)]. Increases in bone mineral density and linear growth were attenuated in QSYMIA- versus placebo-treated patients [see Warnings and Precautions (5.7)]. Serious adverse reactions seen in pediatric patients using topiramate include acute angle glaucoma, oligohidrosis and hyperthermia, metabolic acidosis, cognitive and neuropsychiatric reactions, hyperammonemia and encephalopathy, and kidney stones.

The safety and effectiveness of QSYMIA in pediatric patients below the age of 12 years have not been established.

8.5 Geriatric Use

Additions and/or revisions underlined

In the QSYMIA clinical trials, a total of 254 (7%) of the patients were 65 to 69 years of age; no patients 70 years of age or older were enrolled.

…

8.6 Renal Impairment

Additions and/or revisions underlined

Compared to healthy volunteers with normal renal function, patients with moderate and severe renal impairment as estimated by the Cockcroft-Gault equation had higher exposures to phentermine and topiramate.

The recommended dosage of QSYMIA in patients with mild renal impairment (CrCl greater or equal to 50 and less than 80 mL/min) is the same as the recommended dosage for patients with normal renal function.

…

8.7 Hepatic Impairment

Additions and/or revisions underlined

…

The recommended dosage of QSYMIA in patients with mild hepatic impairment (Child-Pugh 5 - 6) is the same as the recommended dosage in patients with normal hepatic function.

…

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined

…

Ophthalmologic Adverse Reactions

Inform patients that QSYMIA can increase the risk of acute myopia, secondary angle closure glaucoma, and visual field defects. Advise patients to report symptoms of severe and persistent eye pain or significant changes in their vision to their healthcare provider(s) [see Warnings and Precautions (5.4)].

Cognitive Impairment

Inform patients that QSYMIA can cause confusion, concentration, and word-finding difficulties. Inform patients that the concomitant use of alcohol or central nervous system (CNS) depressant drugs with QSYMIA, may increase the risk of dizziness, cognitive adverse reactions, drowsiness, light-headedness, impaired coordination and somnolence.

…

Slowing of Linear Growth

Discuss with the patient and caregiver that long-term QSYMIA treatment may attenuate growth as reflected by slower height increase in pediatric patients [see Warnings and Precautions (5.7)].

…

Risk of Hypotension in Patients Treated with Antihypertensive Medications

Advise patients that weight loss may increase the risk of hypotension. Advise patients to report symptoms of hypotension (e.g., dizziness, lightheadedness, and syncope) to the healthcare provider [see Warnings and Precautions (5.11)].

…

Serious Skin Reactions

Inform patients that serious skin reactions have been reported with use of topiramate, a component of QSYMIA. Inform patients of the signs of serious skin reactions and advise patients to report signs of a skin reaction to their healthcare provider(s) [see Warning and Precautions (5.16)].

…

Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5

Inform patients that this product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons [see Warnings and Precautions (5.17)].

How to Take QSYMIA

Instruct patients on the dosage titration schedule of QSYMIA. Advise patients to take QSYMIA in the morning with or without food [see Dosage and Administration (2.3)].

MEDICATION GUIDE

Extensive additions and/or revisions, please refer to label for complete information.

10/19/2020 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Embryo-Fetal Toxicity

(Additions and revisions underlined)

… Pregnancy testing is recommended before initiating Qsymia treatment in patients who can become pregnant and monthly during Qsymia therapy. Advise patients who can become pregnant of the potential risk to a fetus and to use effective contraception during Qsymia therapy [see Use in Specific Populations (8.1) and (8.3)].

…

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label for complete information)

8.2 Lactation

(PLLR conversion)

Risk Summary

Topiramate and phentermine, components of Qsymia, are present in human milk. There are no data on the effects of topiramate and phentermine on milk production. Diarrhea and somnolence have been reported in breastfed infants with maternal use of topiramate. There are no data on the effects of phentermine in breastfed infants. Because of the potential for serious adverse reactions, including changes in sleep, irritability, hypertension, vomiting, tremor and weight loss in breastfed infants with maternal use of phentermine, advise patients that breastfeeding is not recommended during Qsymia therapy.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Pregnancy Testing

Pregnancy testing is recommended in patients who can become pregnant before initiating Qsymia and monthly during Qsymia therapy [see Warnings and Precautions (5.1), Use in Specific Populations (8.1)].

Contraception

Females

Qsymia can cause fetal harm when administered to a pregnant patient [see Use in Specific Populations (8.1)]. Advise patients who can become pregnant to use effective contraception during therapy with Qsymia.

For patients taking combined oral contraceptives (COCs), use of Qsymia may cause irregular bleeding [see Drug Interactions (7.2)]. Advise patients not to discontinue taking their COC and to contact their healthcare provider.

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

MEDICATION GUIDE

(Additions underlined)

…

Because of the risk for birth defects (cleft lip and cleft palate), Qsymia is available through a restricted program called the Qsymia Risk Evaluation and Mitigation Strategy (REMS). Qsymia is only available through certified pharmacies that participate in the Qsymia REMS program. Your healthcare provider can give you information about how to find a certified pharmacy. For more information, go to www.QsymiaREMS.com or call 1-888- 998-4887

…

What should I tell my healthcare provider before taking Qsymia?

Before taking Qsymia, tell your healthcare provider about all of your medical conditions, including if you:

…

· have type 2 diabetes and take medicine to control your blood sugar.

…

· are breastfeeding or plan to breastfeed. Qsymia can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Qsymia or breastfeed. You should not do both.

…

Especially tell your healthcare provider if you take:

· Birth control pills. Tell your healthcare provider if your menstrual bleeding changes while you are taking birth control pills that contain both estrogen and progestin (combination oral contraceptives) and Qsymia.

…

PATIENT COUNSELING INFORMATION

(Additions underlined)

…

Pregnancy

Qsymia can cause fetal harm and patients should avoid getting pregnant while taking Qsymia [see Warnings and Precautions (5.1), Drug Interactions (7.2), Use in Specific Populations (8.3))].

Advise patients who can become pregnant:

· that pregnancy testing is recommended before initiating Qsymia and monthly during therapy;

· to use effective contraception during Qsymia therapy;

· who experience spotting while taking a combined oral contraceptive to notify their healthcare provider;

· with a known or suspected pregnancy to stop Qsymia immediately and notify their healthcare provider.

Lactation

Advise patients that breastfeeding is not recommended with Qsymia treatment [see Use in Specific Populations (8.2)].

...

03/23/2018 (SUPPL-16)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Elevation in Creatinine

Additions and/or revisions underlined:

Qsymia can cause an increase in serum creatinine that reflects a decrease in renal function (glomerular filtration rate). In phase 3 trials, peak increases in serum creatinine were observed after 4 to 8 weeks of treatment. On average, serum creatinine gradually declined but remained elevated over baseline creatinine values. The changes in serum creatinine (and measured GFR) with short-term Qsymia treatment appear reversible with treatment discontinuation, but the effect of chronic treatment on renal function is not known. Therefore, measurement of …

7 Drug Interactions

7.7 Pioglitazone

Newly added subsection:

A decrease in the exposure of pioglitazone and its active metabolites were noted with the concurrent use of pioglitazone and topiramate in a clinical trial. The clinical relevance of these observations is unknown; however, when Qsymia is added to pioglitazone therapy or pioglitazone is added to Qsymia therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state.