"U.S. Marshals, acting on behalf of the U.S. Food and Drug Administration, today seized tainted dietary supplements from Globe All Wellness, LLC (Globe All), in Hollywood, Fla. The products may be unsafe because they contain an undisclosed active "...
The following important adverse reactions are described below and elsewhere in the labeling:
- Fetal Toxicity: [see WARNINGS AND PRECAUTIONS and Use in Specific Populations]
- Elevation in Heart Rate [see WARNINGS AND PRECAUTIONS]
- Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
- Acute Angle Closure Glaucoma [see WARNINGS AND PRECAUTIONS]
- Mood and Sleep Disorders [see WARNINGS AND PRECAUTIONS]
- Cognitive Impairment [see WARNINGS AND PRECAUTIONS]
- Metabolic Acidosis [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
The data described herein reflects exposure to Qsymia in two, 1-year, randomized, double-blind, placebo-controlled, multicenter clinical trials, and two Phase 2 supportive trials in 2318 adult patients (936 [40.4%] patients with hypertension, 309 [13.3%] patients with type 2 diabetes, 808 [34.9%] patients with BMI greater than 40 kg/m²) exposed for a mean duration of 298 days.
Common Adverse Reactions
Adverse reactions reported in greater than or equal to 2% of Qsymia-treated patients and more frequently than in the placebo group are shown in Table 3.
Table 3: Adverse Reactions Reported in Greater Than or
Equal to 2% of Patients and More Frequently than Placebo during 1 Year of
Treatment – Overall Study Population
|System Organ Class Preferred Term||Placebo
(N = 1561) %
|Qsymia 3.75 mg/23 mg
(N = 240) %
|Qsymia 7.5 mg/46 mg
(N = 498) %
|Qsymia 15 mg/92 mg
(N = 1580) %
|Nervous System Disorders|
|Disturbance in Attention||0.6||0.4||2.0||3.5|
|Gastroesophageal Reflux Disease||1.3||0.8||3.2||2.6|
|General Disorders and Administration Site Conditions|
|Skin and Subcutaneous Tissue Disorders|
|Metabolism and Nutrition Disorders|
|Reproductive System and Breast Disorders|
|Infections and Infestations|
|Upper Respiratory Tract Infection||12.8||15.8||12.2||13.5|
|Urinary Tract Infection||3.6||3.3||5.2||5.2|
|Musculoskeletal and Connective Tissue Disorders|
|Pain in Extremity||2.8||2.1||3.0||3.0|
|Respiratory, Thoracic, and Mediastinal Disorders|
|Injury, Poisoning, and Procedural Complications|
Reports of paraesthesia, characterized as tingling in hands, feet, or face, occurred in 4.2%, 13.7%, and 19.9% of patients treated with Qsymia 3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively, compared to 1.9% of patients treated with placebo. Dysgeusia was characterized as a metallic taste, and occurred in 1.3%, 7.4%, and 9.4% of patients treated with Qsymia 3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively, compared to 1.1% of patients treated with placebo. The majority of these events first occurred within the initial 12 weeks of drug therapy; however, in some patients, events were reported later in the course of treatment. Only Qsymia-treated patients discontinued treatment due to these events (1% for paraesthesia and 0.6% for dysgeusia).
Mood and Sleep Disorders
The proportion of patients in 1-year controlled trials of Qsymia reporting one or more adverse reactions related to mood and sleep disorders was 15.8%, 14.5%, and 20.6% with Qsymia 3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively, compared to 10.3% with placebo. These events were further categorized into sleep disorders, anxiety, and depression. Reports of sleep disorders were typically characterized as insomnia, and occurred in 6.7%, 8.1%, and 11.1% of patients treated with Qsymia 3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively, compared to 5.8% of patients treated with placebo. Reports of anxiety occurred in 4.6%, 4.8%, and 7.9% of patients treated with Qsymia 3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively, compared to 2.6% of patients treated with placebo. Reports of depression/mood problems occurred in 5.0%, 3.8%, and 7.6% of patients treated with Qsymia 3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively, compared to 3.4% of patients treated with placebo. The majority of these events first occurred within the initial 12 weeks of drug therapy; however, in some patients, events were reported later in the course of treatments. In the Qsymia clinical trials, the overall prevalence of mood and sleep adverse reactions was approximately twice as great in patients with a history of depression compared to patients without a history of depression; however, the proportion of patients on active treatment versus placebo who reported mood and sleep adverse reactions was similar in these two subgroups. Occurrence of depression-related events was more frequent in patients with a past history of depression across all treatment groups. However, the placebo-adjusted difference in incidence of these events remained constant between groups regardless of previous depression history.
In the 1-year controlled trials of Qsymia, the proportion of patients who experienced one or more cognitive-related adverse reactions was 2.1% for Qsymia 3.75 mg/23 mg, 5.0% for Qsymia 7.5 mg/46 mg, and 7.6% for Qsymia 15 mg/92 mg, compared to 1.5% for placebo. These adverse reactions were comprised primarily of reports of problems with attention/concentration, memory, and language (word finding). These events typically began within the first 4 weeks of treatment, had a median duration of approximately 28 days or less, and were reversible upon discontinuation of treatment; however, individual patients did experience events later in treatment, and events of longer duration.
In the 1-year controlled trials of Qsymia, the incidence of persistent treatment-emergent decreases in serum bicarbonate below the normal range (levels of less than 21 mEq/L at 2 consecutive visits or at the final visit) was 8.8% for Qsymia 3.75 mg/23 mg, 6.4% for Qsymia 7.5 mg/46 mg, and 12.8% for Qsymia 15 mg/92 mg, compared to 2.1% for placebo. The incidence of persistent, markedly low serum bicarbonate values (levels of less than 17 mEq/L on 2 consecutive visits or at the final visit) was 1.3% for Qsymia 3.75 mg/23 mg, 0.2% for Qsymia 7.5 mg/46 mg dose, and 0.7% for Qsymia 15 mg/92 mg dose, compared to 0.1% for placebo. Generally, decreases in serum bicarbonate levels were mild (average 1-3 mEq/L) and occurred early in treatment (4-week visit), however severe decreases and decreases later in treatment occurred.
In the 1-year controlled trials of Qsymia, the incidence of persistent low serum potassium values (less than 3.5 mEq/L at two consecutive visits or at the final visit) during the trial was 0.4% for Qsymia 3.75 mg/23 mg, 3.6% for Qsymia 7.5 mg/46 mg dose, and 4.9% for Qsymia 15 mg/92 mg, compared to 1.1% for placebo. Of the subjects who experienced persistent low serum potassium, 88% were receiving treatment with a non-potassium sparing diuretic.
The incidence of markedly low serum potassium (less than 3 mEq/L, and a reduction from pre-treatment of greater than 0.5 mEq/L) at any time during the trial was 0.0% for Qsymia 3.75 mg/23 mg, 0.2% for Qsymia 7.5 mg/46 mg dose, and 0.7% for Qsymia 15 mg/92 mg dose, compared to 0.0% for placebo. Persistent markedly low serum potassium (less than 3 mEq/L, and a reduction from pre-treatment of greater than 0.5 mEq/L at two consecutive visits or at the final visit) occurred in 0.0% of subjects receiving Qsymia 3.75 mg/23 mg, 0.2% receiving Qsymia 7.5 mg/46 mg dose, and 0.1% receiving Qsymia 15 mg/92 mg dose, compared to 0.0% receiving placebo.
Hypokalemia was reported by 0.4% of subjects treated with Qsymia 3.75 mg/23 mg, 1.4% of subjects treated with Qsymia 7.5 mg/46 mg, and 2.5% of subjects treated with Qsymia 15 mg/92 mg compared to 0.4% of subjects treated with placebo. “Blood potassium decreased” was reported by 0.4% of subjects treated with Qsymia 3.75 mg/23 mg, 0.4% of subjects treated with Qsymia 7.5 mg/46 mg, 1.0% of subjects treated with Qsymia 15 mg/92 mg, and 0.0% of subjects treated with placebo.
In the 1-year controlled trials of Qsymia, there was a dose-related increase from baseline, peaking between Week 4 to 8, which declined but remained elevated over baseline over 1 year of treatment. The incidence of increases in serum creatinine of greater than or equal to 0.3 mg/dL at any time during treatment was 2.1% for Qsymia 3.75 mg/23 mg, 7.2% for Qsymia 7.5 mg/46 mg, and 8.4% for Qsymia 15 mg/92 mg, compared to 2.0% for placebo. Increases in serum creatinine of greater than or equal to 50% over baseline occurred in 0.8% of subjects receiving Qsymia 3.75 mg/23 mg, 2.0% receiving Qsymia 7.5 mg/46 mg, and 2.8% receiving Qsymia 15 mg/92 mg, compared to 0.6% receiving placebo.
In the 1-year controlled trials of Qsymia, the incidence of nephrolithiasis was 0.4% for Qsymia 3.75 mg/23 mg, 0.2% for Qsymia 7.5 mg/46 mg, and 1.2% for Qsymia 15 mg/92 mg, compared to 0.3% for placebo.
Drug Discontinuation Due to Adverse Reactions
In the 1-year placebo-controlled clinical studies, 11.6% of Qsymia 3.75 mg/23 mg, 11.6% of Qsymia 7.5 mg/46 mg, 17.4% of Qsymia 15 mg/92 mg, and 8.4% of placebo-treated patients discontinued treatment due to reported adverse reactions. The most common adverse reactions that led to discontinuation of treatment are shown in Table 4.
Table 4: Adverse Reactions Greater Than or Equal To 1%
Leading to Treatment Discontinuation (1-Year Clinical Trials)
|Adverse Reaction Leading to Treatment Discontinuationa||Placebo
|Qsymia 3.75 mg/23 mg
|Qsymia 7.5 mg/46 mg
|Qsymia 15 mg/92 mg
|a greater than or equal to 1% in any treatment group|
The following adverse reactions have been reported during post approval use of phentermine and topiramate, the components of Qsymia. 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.
Suicidal ideation, Suicidal behavior
Acute angle closure glaucoma
Increased intraocular pressure
Allergic Adverse Reactions
Cardiovascular Adverse Reactions
Elevation of blood pressure, Ischemic events
Central Nervous System Adverse Reactions
Reproductive Adverse Reactions
Hepatic failure (including fatalities), Hepatitis
Read the Qsymia (phentermine and topiramate) Side Effects Center for a complete guide to possible side effects
Monoamine Oxidase Inhibitors
Use of phentermine is contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors because of the risk of hypertensive crisis.
Co-administration of multiple-dose Qsymia 15 mg/92 mg once daily with a single dose of oral contraceptive containing 35 μg ethinyl estradiol (estrogen component) and 1 mg norethindrone (progestin component), in obese otherwise healthy volunteers, decreased the exposure of ethinyl estradiol by 16% and increased the exposure of norethindrone by 22% [see CLINICAL PHARMACOLOGY].
Although this study did not specifically address the impact of the interaction on contraceptive efficacy, an increased risk of pregnancy is not anticipated. The primary determinant of contraceptive efficacy is the progestin component of the combination oral contraceptive, so higher exposure to the progestin would not be expected to be deleterious.
However, irregular bleeding (spotting) may occur more frequently due to both the increased exposure to the progestin and lower exposure to the estrogen, which tends to stabilize the endometrium. Patients should be informed not to discontinue their combination oral contraceptive if spotting occurs, but to notify their healthcare provider if the spotting is troubling to them.
CNS Depressants Including Alcohol
Specific drug interaction studies of Qsymia and alcohol or other CNS depressant drugs have not been performed. The concomitant use of alcohol or CNS depressant drugs (e.g., barbiturates, benzodiazepines, and sleep medications) with phentermine or topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Therefore, if Qsymia is used with alcohol or other CNS depressants, the patient should be counseled regarding possible increased risk of CNS depression or side effects.
Non-Potassium Sparing Diuretics
Concurrent use of Qsymia with non-potassium sparing diuretics may potentiate the potassium-wasting action of these diuretics. Concomitant administration of hydrochlorothiazide alone with topiramate alone has been shown to increase the Cmax and AUC of topiramate by 27% and 29%, respectively. When prescribing Qsymia in the presence of non-potassium-sparing medicinal products, patients should be monitored for hypokalemia [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Concomitant administration of phenytoin or carbamazepine with topiramate in patients with epilepsy, decreased plasma concentrations of topiramate by 48% and 40%, respectively, when compared to topiramate given alone [see CLINICAL PHARMACOLOGY].
Concomitant administration of valproic acid and topiramate has been associated with hyperammonemia with and without encephalopathy. Concomitant administration of topiramate with valproic acid in patients has also been associated with hypothermia (with and without hyperammonemia). It may be prudent to examine blood ammonia in patients in whom the onset of hypothermia or encephalopathy has been reported [see CLINICAL PHARMACOLOGY].
Carbonic Anhydrase Inhibitors
Concomitant use of topiramate, a component of Qsymia, with any other carbonic anhydrase inhibitor (e.g., zonisamide, acetazolamide, or dichlorphenamide) may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation. Avoid the use of Qsymia with other drugs that inhibit carbonic anhydrase [see WARNINGS AND PRECAUTIONS].
Drug Abuse And Dependence
Qsymia is controlled in Schedule IV of the Controlled Substances Act because it contains phentermine a Schedule IV drug. Any material, compound, mixture, or preparation that contains any quantity of phentermine is controlled as a Schedule IV drug.
Topiramate is not controlled in the Controlled Substances Act.
Phentermine, a component of Qsymia, has a known potential for abuse.
Phentermine, a component of Qsymia, is related chemically and pharmacologically to the amphetamines. Amphetamines and other stimulant drugs have been extensively abused and the possibility of abuse of phentermine should be kept in mind when evaluating the desirability of including Qsymia as part of a weight reduction program. Abuse of amphetamines and related drugs (e.g., phentermine) may be associated with impaired control over drug use and severe social dysfunction. There are reports of patients who have increased the dosage of these drugs to many times than recommended.
Qsymia has not been systematically studied for its potential to produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use. Physical dependence manifests by drug-class-specific withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Limited information on the potential for physical dependence for the individual components of Qsymia is available. For topiramate, abrupt discontinuation has been associated with seizures in patients without a history of seizures or epilepsy. For phentermine, abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on a sleep electroencephalogram. Thus, in situations where rapid withdrawal of Qsymia is required, appropriate medical monitoring is recommended.
Read the Qsymia Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 10/9/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Qsymia Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.