Qsymia

— THERAPEUTIC CATEGORIES —
  • Obesity
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Qsymia Generic Name & Formulations

    Legal Class

    CIV

    General Description

    Phentermine HCl/topiramate extended-release; 3.75mg/23mg, 7.5mg/46mg, 11.25mg/69mg, 15mg/92mg; caps; contains tartrazine.

    Pharmacological Class

    Sympathomimetic amine + antiepileptic.

    How Supplied

    Caps 3.75mg/23mg—14, 30; 7.5mg/46mg, 11.25mg/69mg, 15mg/92mg—30; Starter Pack (3.75mg/23mg + 7.5mg/46mg)—28; Dose Escalation Pack (11.25mg/69mg + 15mg/92mg)—28

    How Supplied

    Qsymia is supplied as:

    • Caps 3.75mg/23mg (purple cap imprinted with VIVUS, purple
      body imprinted with 3.75/23) in bottles of 14, 30; 

    • Caps 7.5mg/46mg (purple cap imprinted with VIVUS, yellow body imprinted with 7.5/46), 11.25mg/69mg (yellow cap imprinted with
      VIVUS, yellow body imprinted with 11.25/69), 15mg/92mg (yellow cap imprinted with VIVUS, white body imprinted with 15/92) in bottles of 30; 

    • Starter Pack (3.75mg/23mg + 7.5mg/46mg) in blisters of 28; 

    • Dose Escalation Pack (11.25mg/69mg + 15mg/92mg) in blisters of 28.

    Storage

    Store at 20° C to 25° C (68° F to 77° F), excursions permitted between 15° C and 30° C (59° F and 86° F).  

    Keep container tightly closed and protect from moisture.

    Manufacturer

    Vivus, Inc.

    Generic Availability

    NO

    Mechanism of Action

    The effect of phentermine on chronic weight management is likely mediated by release of catecholamines in the hypothalamus, resulting in reduced appetite and decreased food consumption, but other metabolic effects may also be involved.

    The effect of topiramate may be due to its effects on both appetite suppression and satiety enhancement, induced by a combination of pharmacologic effects including augmenting the activity of the neurotransmitter gamma-aminobutyrate, modulation of voltage-gated ion channels, inhibition of AMPA/kainite excitatory glutamate receptors, or inhibition of carbonic anhydrase.

    Qsymia Indications

    Indications

    As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in: adults with an initial BMI of ≥30kg/m2 or ≥27kg/m2 in the presence of at least one weight related co-morbidity (eg, hypertension, type 2 diabetes, or dyslipidemia); or pediatric patients aged ≥12yrs with BMI in the 95th percentile or greater standardized for age and sex.

    Limitations of Use

    Effects on cardiovascular morbidity/mortality not established. Safety, effectiveness in combination with other weight loss products not established.

    Limitations of Use Expanded

    The effect of phentermine HCl/topiramate on cardiovascular morbidity and mortality has not been established. 

    The safety and effectiveness of phentermine HCl/topiramate in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.

    Qsymia Dosage and Administration

    Prior to Treatment Evaluations

    Obtain a negative pregnancy test before initiating phentermine HCl/topiramate in patients who can become pregnant and monthly during phentermine HCl/topiramate therapy. 

    Obtain a blood chemistry profile that includes bicarbonate, creatinine, and potassium in all patients, and glucose in patients with type 2 diabetes on antidiabetic medication prior to initiating phentermine HCl/topiramate treatment and periodically during treatment.

    Adults and Children

    <12yrs: not established. Take once daily in the AM. ≥12yrs: Initially 3.75mg/23mg for 14 days; then increase to 7.5mg/46mg and evaluate weight loss after 12 weeks on this dose. If patient has not lost ≥3% baseline body wt. or BMI, increase to 11.25mg/69mg for 14 days; followed by an increase to 15mg/92mg and evaluate weight loss after 12 weeks on this dose. If patient has not lost ≥5% baseline body wt. or BMI, discontinue by taking 15mg/92mg every other day for at least 1 week prior to stopping altogether. Consider dose reduction if weight loss exceeds 2lbs (0.9kg) per week. Renal (moderate or severe), hepatic (moderate) impairment: max 7.5mg/46mg once daily.

    Renal impairment

    In patients with severe (CrCl <30 mL/min) or moderate (CrCl ≥30-<50 mL/min) renal impairment: maximum dosage is 7.5 mg/46 mg once daily.

    Hepatic Impairment

    In patients with moderate hepatic impairment (Child-Pugh score 7–9): maximum dosage is 7.5 mg/46 mg once daily.

    Qsymia Contraindications

    Contraindications

    Pregnancy. Glaucoma. Hyperthyroidism. During or within 14 days of MAOIs.

    Qsymia Boxed Warnings

    Not Applicable

    Qsymia Warnings/Precautions

    Warnings/Precautions

    Embryo-fetal toxicity: obtain a negative pregnancy test before initiating and monthly during therapy; advise females of reproductive potential to use effective contraception. Recent or unstable cardiac or cerebrovascular disease: not recommended. Measure resting heart rate regularly. History of suicidal attempts or active suicidal ideation: avoid. Monitor for worsening of depression, suicidal thoughts, unusual behaviors; discontinue if occurs. History of depression. Sleep disorders. Discontinue if acute myopia and secondary angle-closure glaucoma syndrome occur. Consider discontinuing if visual field defects occur. Kidney stones. Maintain adequate hydration; avoid ketogenic diets. Measure electrolytes including serum bicarbonate, potassium, creatinine, blood glucose (in diabetics), BP (in patients on antihypertensives) prior to starting and during therapy. Monitor height velocity in children. Monitor for decreased sweating and increased body temperature during physical activity. Discontinue at the 1st sign of a rash. Avoid abrupt withdrawal (seizure risk). ESRD on dialysis, severe hepatic impairment: avoid. Elderly. Nursing mothers: not recommended.

    Warnings/Precautions

    Embryo-Fetal Toxicity 

    Qsymia can cause fetal harm. 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.

    Increase in Heart Rate

    Qsymia can cause an increase in resting heart rate. Measure resting heart rate regularly in all patients taking Qsymia, especially those with cardiac or cerebrovascular disease and when initiating or increasing the dosage of Qsymia. 

    Qsymia has not been studied in patients with recent or unstable cardiac or cerebrovascular disease and therefore use is not recommended.   

    For patients who experience a sustained increase in resting heart rate while taking Qsymia, reduce the dosage or discontinue Qsymia.

    Suicidal Behavior and Ideation

    Monitor all patients for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Qsymia in patients who experience suicidal thoughts or behaviors. Avoid Qsymia in patients with a history of suicidal attempts or active suicidal ideation. 

    Risk of Ophthalmologic Adverse Reactions  

    • 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. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Discontinue immediately if acute myopia and secondary angle-closure glaucoma syndrome develops. 

    • 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. If visual problems occur at any time during treatment, consider discontinuing Qsymia. 

    Mood and Sleep Disorders

    Qsymia can cause mood disorders, including depression and anxiety, as well as insomnia. Patients with a history of depression may be at increased risk of recurrent depression or other mood disorders while taking Qsymia. Consider dosage reduction or discontinuation of Qsymia if clinically significant or persistent symptoms occur. Discontinue Qsymia if patients have symptoms of suicidal ideation or behavior.

    Cognitive Impairment  

    Qsymia can cause cognitive dysfunction (eg, 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. If cognitive dysfunction persists, consider dosage reduction or discontinuation of Qsymia. 

    Slowing of Linear Growth 

    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. 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.

    Metabolic Acidosis

    Hyperchloremic, non-anion gap, metabolic acidosis has been reported in patients treated with Qsymia.

    Conditions or therapies that predispose to acidosis (eg., renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, or ketogenic diet) may be additive to the bicarbonate lowering effects of Qsymia.

    Measure electrolytes including serum bicarbonate prior to starting and during Qsymia treatment. If persistent metabolic acidosis develops while taking Qsymia, reduce the dosage or discontinue Qsymia.

    Decrease in Renal Function 

    Qsymia can cause an increase in serum creatinine that reflects a decrease in renal function.

    Measure serum creatinine prior to starting and during Qsymia treatment. If persistent elevations in creatinine occur, reduce the dosage or discontinue Qsymia.

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

    Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (eg., sulfonylureas). Qsymia has not been studied in combination with insulin. Measure blood glucose levels prior to starting 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.

    Risk of Hypotension in Patients Treated with Antihypertensive Medications

    In hypertensive patients being treated with antihypertensive medications, weight loss may increase the risk of hypotension and associated symptoms including dizziness, lightheadedness, and syncope. Measure blood pressure prior to starting and during Qsymia treatment in patients being treated for hypertension. If a patient develops symptoms associated with low blood pressure after starting Qsymia, appropriate changes should be made to the antihypertensive drug regimen.

    Risk of Seizures with Abrupt Withdrawal of Qsymia

    Abrupt withdrawal of topiramate has been associated with seizures in individuals without a history of seizures or epilepsy. Patients discontinuing Qsymia 15 mg/92 mg should be gradually tapered to reduce the possibility of precipitating a seizure.

    Kidney Stones

    Qsymia has been associated with kidney stone formation. Topiramate inhibits carbonic anhydrase activity and promotes kidney stone formation by reducing urinary citrate excretion and increasing urine pH.

    Avoid the use of Qsymia with other drugs that inhibit carbonic anhydrase. Advise patients to increase fluid intake (to increase urinary output), which may decrease the concentration of substances involved in kidney stone formation.

    Avoid ketogenic diets. 

    Oligohidrosis and Hyperthermia

    Oligohidrosis (decreased sweating), infrequently resulting in hospitalization, has been reported in association with the use of topiramate. Decreased sweating and an elevation in body temperature above normal characterized these cases. Some of the cases have been reported with topiramate after exposure to elevated environmental temperatures. 

    The majority of the reports associated with topiramate have been in pediatric patients. Advise patients 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. 

    Hypokalemia

    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.

    Serious Skin Reactions

    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.

    Pregnancy Considerations

    The use of Qsymia can cause fetal harm and weight loss offers no clear clinical benefit to a pregnant patient. Available data from 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 small for gestational age in infants exposed in utero to topiramate.

    Advise pregnant women of the potential risk to a fetus.

    Nursing Mother Considerations

    Topiramate and phentermine, components of Qsymia, are present in human milk. There is no data on the effects of topiramate and phentermine on milk production. 

    There is 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.

    Pediatric Considerations

    The safety and effectiveness of Qsymia in pediatric patients <12 years of age have not been established.

    Geriatric Considerations

    Clinical studies of Qsymia did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    Renal Impairment Considerations

    Qsymia has not been studied in patients with end-stage renal disease on dialysis. Avoid Qsymia in this patient population.

    Hepatic Impairment Considerations

    Qsymia has not been studied in patients with severe hepatic impairment (Child-Pugh score 10–15). Avoid Qsymia in this patient population.

    REMS

    YES

    Qsymia Pharmacokinetics

    Distribution

    Phentermine is 17.5% plasma protein bound. The estimated phentermine apparent volume of distribution (Vd/F) is 348 L via population pharmacokinetic analysis. 

    Topiramate is 15-41% plasma protein bound over the blood concentration range of 0.5 to 250 µg/mL. The estimated topiramate Vc/F (volume of the central compartment), and Vp/F (volume of the peripheral compartment) are 50.8 L, and 13.1 L, respectively, via population pharmacokinetic analysis.

    Metabolism

    Phentermine has two metabolic pathways, namely p-hydroxylation on the aromatic ring and N-oxidation on the aliphatic side chain. Cytochrome P450 (CYP) 3A4 primarily metabolizes phentermine but does not show extensive metabolism. 

    Topiramate does not show extensive metabolism. Six topiramate metabolites (via hydroxylation, hydrolysis, and glucuronidation) exist, none of which constitutes more than 5% of an administered dose.

    Elimination

    Seventy to 80% of a dose exists as unchanged phentermine in urine when administered alone. The mean terminal half-life is about 20 hours.

    About 70% of a dose exists as unchanged topiramate in urine when administered alone. The mean terminal half-life is about 65 hours.

    Qsymia Interactions

    Interactions

    See Contraindications. May potentiate CNS depression with concomitant alcohol or other CNS depressants (eg, barbiturates, benzodiazepines, hypnotics). Avoid excessive alcohol intake. Increased risk of hypokalemia with concomitant non-K+-sparing diuretics (eg, furosemide, HCTZ). Avoid other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, methazolamide). Hyperammonemia (w/ or w/o encephalopathy) and/or hypothermia possible with valproic acid. May be antagonized by phenytoin, carbamazepine. May antagonize pioglitazone (monitor glucose control). May affect oral contraceptives (spotting may occur). May potentiate amitriptyline.

    Interactions

    Concomitant use of phentermine with monoamine oxidase inhibitors (MAOIs) increases the risk of hypertensive crisis. Concomitant use of Qsymia is contraindicated during MAOI treatment and within 14 days of stopping an MAOI.

    Co-administration with a single dose of oral contraceptive containing 35 µg ethinyl estradiol and 1 mg norethindrone, in obese otherwise healthy volunteers, decreased the exposure of ethinyl estradiol by 16% and increased the exposure of norethindrone by 22%. Although this interaction is not anticipated to increase the risk of pregnancy, irregular bleeding (spotting) may occur more frequently. Advise patients not to discontinue their combination oral contraceptive if spotting occurs.

    The concomitant use of alcohol or CNS depressant drugs (eg, barbiturates, benzodiazepines, and sleep medications) with phentermine or topiramate may potentiate CNS depression. Caution patients against excessive alcohol intake when taking Qsymia. Consider Qsymia dosage reduction or discontinuation if cognitive dysfunction persists.

    Concurrent use of Qsymia with non-potassium sparing diuretics may potentiate the potassium-wasting action of these diuretics. When Qsymia is used concomitantly with non-potassium-sparing diuretics, measure potassium before and during Qsymia treatment.

    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. 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). Consider measuring blood ammonia in patients in whom the onset of hypothermia or encephalopathy has been reported.

    Concomitant use of topiramate with any other carbonic anhydrase inhibitor 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 (eg, zonisamide, acetazolamide, methazolamide). If concomitant use of Qsymia with another carbonic anhydrase inhibitor is unavoidable, monitor the patient for the appearance or worsening of metabolic acidosis.

    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. Consider increased glycemic monitoring when using pioglitazone and QSYMIA concomitantly.

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

    Qsymia Adverse Reactions

    Adverse Reactions

    Paraesthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth; also in children: depression, arthralgia, pyrexia, influenza, ligament sprain; cognitive impairment, metabolic acidosis, increased serum creatinine, oligohidrosis, hyperthermia, serious skin reactions (eg, SJS, TEN).

    Adverse Reactions

    Most common adverse reactions in:

    • Adults (incidence ≥5% and at least 1.5 times placebo) are: paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.

    • Pediatric patients aged 12 years and older (incidence ≥4% and greater than placebo) are: depression, dizziness, arthralgia, pyrexia, influenza, and ligament sprain.

    Qsymia Clinical Trials

    Clinical Trials

    Clinical Studies in Adults  

    The effect of Qsymia on weight loss in conjunction with reduced caloric intake and increased physical activity was studied in 2 randomized, double-blind, placebo-controlled studies in patients with obesity (Study 1) and patients with obesity or overweight with 2 or more significant co-morbidities (Study 2). Both studies had a 4-week titration period, followed by 52 weeks of treatment.

    There were 2 co-primary efficacy outcomes measured after 1 year of treatment (Week 56):

    • the percent weight loss from baseline;
    • treatment response defined as achieving at least 5% weight loss from baseline.

    In Study 1, patients with obesity (BMI ≥35 kg/m2) were randomized to receive 1 year of treatment with placebo (n=514), Qsymia 3.75 mg/23 mg (n=241), or Qsymia 15 mg/92 mg (n=512) in a 2:1:2 ratio. At the beginning of the study the average weight and BMI of patients was 116 kg and 42 kg/m2, respectively. Patients with type 2 diabetes were excluded from participating in Study 1. During the study, a well-balanced, reduced-calorie diet to result in an approximate 500 kcal/day decrease in caloric intake was recommended to all patients and patients were offered nutritional and lifestyle modification counseling.

    In Study 2, patients with overweight or obesity were randomized to receive 1 year of treatment with placebo (n=994), Qsymia 7.5 mg/46 mg (n=498), or Qsymia 15 mg/92 mg (n=995) in a 2:1:2 ratio. Eligible patients had to have a BMI ≥27 kg/m2 and ≤45 kg/m2 (there was no lower limit on BMI for patients with type 2 diabetes) and two or more of the following obesity-related comorbid conditions:

    • Elevated blood pressure (≥140/90 mmHg, or ≥130/85 mmHg for diabetics) or requirement for ≥2 antihypertensive medications;
    • Triglycerides greater than 200-400 mg/dL or were receiving treatment with 2 or more lipid-lowering agents;
    • Elevated fasting blood glucose (greater than 100 mg/dL) or diabetes; and/or
    • Waist circumference greater than or equal to 102 cm for men or greater than or equal to 88 cm for women.

    The average weight and BMI of patients at the start of the study was 103 kg and 36.6 kg/m2, respectively. Approximately half (53%) of patients had hypertension at the start of the study. There were 388 (16%) patients with type 2 diabetes at the start of the study. During the study, a well-balanced, reduced-calorie diet to result in an approximate 500 kcal/day decrease in caloric intake was recommended to all patients and patients were offered nutritional and lifestyle modification counseling. 

    After 1 year of treatment with Qsymia, all dose levels resulted in statistically significant weight loss compared to placebo. A statistically significant greater proportion of the patients randomized to Qsymia than placebo achieved 5% and 10% weight loss. The following are the results observed for weight loss at 1 year in Studies 1 and 2 of patients treated with Qsymia doses compared to placebo:

    Study 1 (Obesity)
    Qsymia 3.75 mg/23 mg and Qsymia 15 mg/92 mg vs Placebo, respectively:

    • Weight % mean change from baseline:  -5.1 and -10.9 vs -1.6; difference from placebo:  3.5 (95% CI, 2.4-4.7; P <.0001) and 9.4 (95% CI, 8.4-10.3; P <.0001)
    • Percentage of patients losing ≥5% body weight:  45% and 67% vs 17%; risk difference vs placebo:  27.6 (95% CI, 20.4-34.8; P <.0001) and 49.4 (95% CI, 44.1-54.7; P <.0001)
    • Percentage of patients losing ≥10% body weight:  19% and 47% vs 7%; risk difference vs placebo:  11.4 (95% CI, 5.9-16.9; P <.0001) and 39.8 (95% CI, 34.8-44.7; P <.0001)

    Study 2 (Obesity or overweight with comorbidities)
    Qsymia 7.5 mg/46 mg and Qsymia 15 mg/92 mg vs Placebo, respectively:

    • Weight % mean change from baseline:  -7.8 and -9.8 vs -1.2; difference from placebo:  6.6 (95% CI, 5.8-7.4; P <.0001) and 8.6 (95% CI, 8.0-9.3; P <.0001)
    • Percentage of patients losing ≥5% body weight:  62% and 70% vs 21%; risk difference vs placebo:  41.3 (95% CI, 36.3-46.3; P <.0001) and 49.2 (95% CI, 45.4-53.0; P <.0001)
    • Percentage of patients losing ≥10% body weight:  37% and 48% vs 7%; risk difference vs placebo:  29.9 (95% CI, 25.3-34.5; P <.0001) and 40.3 (95% CI, 36.7-43.8; P <.0001)

     

    Clinical Studies in Pediatric Patients Aged 12 Years and Older 

    The effect of Qsymia on BMI in conjunction with reduced caloric intake and increased physical activity was evaluated in Study 3 (NCT 03922945), a 56-week, randomized, double-blind, placebo-controlled study in pediatric patients (12-17 years of age) with BMI ≥ 95th percentile standardized by age and sex. Patients were randomized to receive treatment with placebo (n=56), Qsymia 7.5 mg/46 mg (n=54), or Qsymia 15 mg/92 mg (n=113) in a 1:1:2 ratio. During the study, a well-balanced, reduced-calorie diet to result in an approximate 500 kcal/day decrease in caloric intake was recommended to all patients and patients were offered a family-based lifestyle modification program for adolescents.

    At the beginning of the study, the average weight and BMI of patients was 106 kg and 38 kg/m2, respectively, with approximately 81% considered severely obese (120% of the 95th percentile or greater for BMI standardized by age and sex). Thirty-eight (38%) of randomized patients withdrew from the study prior to week 56. 

    The primary efficacy parameter was mean percent change in BMI. After 56 weeks of treatment with Qsymia, all dose levels resulted in statistically significant reduction in BMI compared to placebo. A greater proportion of patients randomized to Qsymia than placebo achieved 5%, 10%, and 15% BMI reduction. The following are the results observed for BMI reduction at week 56 in Study 3:

    Study 3 (Obesity)
    Qsymia 7.5 mg/46 mg and Qsymia 15 mg/92 mg vs Placebo, respectively:

    • BMI (primary endpoint) % mean change from baseline:  -4.8 and -7.1 vs +3.3; difference from placebo:  -8.1 (95% CI, -11.9, -4.3) and -10.4 (95% CI, -13.9, -7.0)
    • Percentage of patients with a reduction of ≥5% BMI:  44% and 52.2% vs 13.6%; difference vs placebo:  29.7% (95% CI, 11.2-48.3) and 38.6% (95% CI, 23.1-54.1)
    • Percentage of patients with a reduction of ≥10% BMI:  33.5% and 44.4% vs 4.5%; difference vs placebo:  28.8% (95% CI, 13.6-44.0) and 40.5% (95% CI, 28.4-52.6)
    • Percentage of patients with a reduction of ≥15% BMI:  13.6% and 28.9% vs 2.9%; difference vs placebo:  11.7% (95% CI, 1.3-22.2) and 27.4% (95% CI, 17.7-37.1)

    For more clinical trial data, see full labeling.

    Qsymia Note

    Notes

    Only available through certified pharmacies enrolled in the Qsymia REMS program. For more information call (888) 998-4887.

    Qsymia Patient Counseling

    Patient Counseling

    Embryo-Fetal Toxicity 

    Inform patients who can become pregnant that Qsymia can cause fetal harm and patients should avoid getting pregnant while taking Qsymia. 

    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. 

    Increase in Heart Rate 

    Inform patients that Qsymia can increase resting heart rate. Advise patients to report palpitations or feelings of a racing heartbeat while at rest to their healthcare provider(s). 

    Suicidal Behavior and Ideation and Mood and Sleep Disorders 

    Inform patients that Qsymia can increase the risk of mood changes, sleep disorders, depression, and suicidal ideation. Advise patients to tell their healthcare provider(s) immediately if mood changes, depression, or suicidal ideation occur. 

    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). 

    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. 

    Advise patients to tell their healthcare provider(s) about any changes in attention, concentration, memory, difficulty finding words, or other cognitive functions.

    Advise patients not to drive or operate machinery until they have gained sufficient experience on Qsymia to gauge whether it adversely affects their mental performance, motor performance, and/or vision. Advise patients to avoid excessive alcohol intake while taking Qsymia.

    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. 

    Metabolic Acidosis 

    Inform patients that Qsymia can increase the risk of metabolic acidosis. Advise patients to tell their healthcare provider(s) about any factors that can increase the risk of acidosis (eg, prolonged diarrhea, surgery, and high protein/low carbohydrate diet, and/or concomitant medications such as carbonic anhydrase inhibitors). 

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

    Inform patients that weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (eg, sulfonylureas). Advise patients with type 2 diabetes mellitus on antidiabetic therapy to monitor their blood glucose levels and report symptoms of hypoglycemia to their healthcare provider(s). 

    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 (eg, dizziness, lightheadedness, and syncope) to the healthcare provider. 

    Risk of Seizures with Abrupt Withdrawal of Qsymia 

    Inform patients that abrupt withdrawal of topiramate, a component of Qsymia, has been associated with seizures in individuals without a history of seizures or epilepsy. Advise patients not to abruptly stop Qsymia without first talking to their healthcare provider(s).

    Kidney Stones 

    Inform patients that use of Qsymia has been associated with kidney stone formation. Advise patients to increase fluid intake to increase urinary output which can decrease the concentration of substances involved in kidney stone formation. Advise patients to report symptoms of severe side or back pain, and/or blood in their urine to their healthcare provider(s). 

    Oligohidrosis and Hyperthermia 

    Inform patients that oligohidrosis (decreased sweating) has been reported in association with the use of topiramate, a component of Qsymia, particularly in pediatric patients. Advise patients to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather. 

    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).

    Lactation 

    Advise patients that breastfeeding is not recommended during Qsymia treatment.

     

    Cost Savings Program

    The Qsymia savings program is available here.

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