QSYMIA SIDE EFFECTS
- Generic Name: phentermine and topiramate
- Brand Name: Qsymia
- Drug Class: Stimulants
SIDE EFFECTS
The following important adverse reactions are described below and elsewhere in the labeling:
- Fetal Toxicity
- Elevation in Heart Rate
- Suicidal Behavior and Ideation
- Acute Angle Closure Glaucoma
- Mood and Sleep Disorders
- Cognitive Impairment
- Metabolic Acidosis
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 occurring at a rate of greater than or equal to 5% and at a rate at least 1.5 times placebo include paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.
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 1.
Table 1. 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 | ||||
| Paraesthesia | 1.9 | 4.2 | 13.7 | 19.9 |
| Headache | 9.3 | 10.4 | 7.0 | 10.6 |
| Dizziness | 3.4 | 2.9 | 7.2 | 8.6 |
| Dysgeusia | 1.1 | 1.3 | 7.4 | 9.4 |
| Hypoesthesia | 1.2 | 0.8 | 3.6 | 3.7 |
| Disturbance in Attention | 0.6 | 0.4 | 2.0 | 3.5 |
| Psychiatric Disorders | ||||
| Insomnia | 4.7 | 5.0 | 5.8 | 9.4 |
| Depression | 2.2 | 3.3 | 2.8 | 4.3 |
| Anxiety | 1.9 | 2.9 | 1.8 | 4.1 |
| Gastrointestinal Disorders | ||||
| Constipation | 6.1 | 7.9 | 15.1 | 16.1 |
| Dry Mouth | 2.8 | 6.7 | 13.5 | 19.1 |
| Nausea | 4.4 | 5.8 | 3.6 | 7.2 |
| Diarrhea | 4.9 | 5.0 | 6.4 | 5.6 |
| Dyspepsia | 1.7 | 2.1 | 2.2 | 2.8 |
| Gastroesophageal Reflux Disease | 1.3 | 0.8 | 3.2 | 2.6 |
| Paraesthesia Oral | 0.3 | 0.4 | 0.6 | 2.2 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 4.3 | 5.0 | 4.4 | 5.9 |
| Irritability | 0.7 | 1.7 | 2.6 | 3.7 |
| Thirst | 0.7 | 2.1 | 1.8 | 2.0 |
| Chest Discomfort | 0.4 | 2.1 | 0.2 | 0.9 |
| Eye Disorders | ||||
| Vision Blurred | 3.5 | 6.3 | 4.0 | 5.4 |
| Eye Pain | 1.4 | 2.1 | 2.2 | 2.2 |
| Dry Eye | 0.8 | 0.8 | 1.4 | 2.5 |
| Cardiac Disorders | ||||
| Palpitations | 0.8 | 0.8 | 2.4 | 1.7 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Rash | 2.2 | 1.7 | 2.0 | 2.6 |
| Alopecia | 0.7 | 2.1 | 2.6 | 3.7 |
| Metabolism and Nutrition Disorders | ||||
| Hypokalemia | 0.4 | 0.4 | 1.4 | 2.5 |
| Decreased Appetite | 0.6 | 2.1 | 1.8 | 1.5 |
| Reproductive System and Breast Disorders | ||||
| Dysmenorrhea | 0.2 | 2.1 | 0.4 | 0.8 |
| Infections and Infestations | ||||
| Upper Respiratory Tract Infection | 12.8 | 15.8 | 12.2 | 13.5 |
| Nasopharyngitis | 8.0 | 12.5 | 10.6 | 9.4 |
| Sinusitis | 6.3 | 7.5 | 6.8 | 7.8 |
| Bronchitis | 4.2 | 6.7 | 4.4 | 5.4 |
| Influenza | 4.4 | 7.5 | 4.6 | 4.4 |
| Urinary Tract Infection | 3.6 | 3.3 | 5.2 | 5.2 |
| Gastroenteritis | 2.2 | 0.8 | 2.2 | 2.5 |
| Musculoskeletal and Connective Tissue Disorders | ||||
| Back Pain | 5.1 | 5.4 | 5.6 | 6.6 |
| Pain in Extremity | 2.8 | 2.1 | 3.0 | 3.0 |
| Muscle Spasms | 2.2 | 2.9 | 2.8 | 2.9 |
| Musculoskeletal Pain | 1.2 | 0.8 | 3.0 | 1.6 |
| Neck Pain | 1.3 | 1.3 | 2.2 | 1.2 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||||
| Cough | 3.5 | 3.3 | 3.8 | 4.8 |
| Sinus Congestion | 2.0 | 2.5 | 2.6 | 2.0 |
| Pharyngolaryngeal Pain | 2.0 | 2.5 | 1.2 | 2.3 |
| Nasal Congestion | 1.4 | 1.7 | 1.2 | 2.0 |
| Injury, Poisoning, and Procedural Complications | ||||
| Procedural Pain | 1.7 | 2.1 | 2.4 | 1.9 |
Paraesthesia/Dysgeusia
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.
Cognitive Disorders
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.
Laboratory Abnormalities
Serum Bicarbonate
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.
Serum Potassium
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.
Serum Creatinine
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.
Nephrolithiasis
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 2.
Table 2. Adverse Reactions Greater Than or Equal To 1% Leading to Treatment Discontinuation (1-Year Clinical Trials)
| Adverse Reaction Leading to Treatment Discontinuationa | 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) % |
| Vision blurred | 0.5 | 2.1 | 0.8 | 0.7 |
| Headache | 0.6 | 1.7 | 0.2 | 0.8 |
| Irritability | 0.1 | 0.8 | 0.8 | 1.1 |
| Dizziness | 0.2 | 0.4 | 1.2 | 0.8 |
| Paraesthesia | 0.0 | 0.4 | 1.0 | 1.1 |
| Insomnia | 0.4 | 0.0 | 0.4 | 1.6 |
| Depression | 0.2 | 0.0 | 0.8 | 1.3 |
| Anxiety | 0.3 | 0.0 | 0.2 | 1.1 |
| a greater than or equal to 1% in any treatment group | ||||
Postmarketing Experience
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.
Qsymia
Psychiatric Disorders
Suicidal ideation, Suicidal behavior
Ophthalmic Disorders
Acute angle closure glaucoma
Increased intraocular pressure
Phentermine
Allergic Adverse Reactions
Urticaria
Cardiovascular Adverse Reactions
Elevation of blood pressure, Ischemic events
Central Nervous System Adverse Reactions
Euphoria, Psychosis, Tremor
Reproductive Adverse Reactions
Changes in libido, Impotence
Topiramate
Dermatologic Disorders
Bullous skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), Pemphigus
Gastrointestinal Disorders
Pancreatitis
Hepatic Disorders
Hepatic failure (including fatalities), Hepatitis
Metabolic Disorders
Hyperammonemia
Hypothermia
Ophthalmic Disorders
Maculopathy
SRC: NLM .