General

**REMS Drug**

Pronunciation:
fen-ter-meen/toe-pyre-a-mate

Trade Name(s)

• Qsymia

Ther. Class.

weight control agents

Pharm. Class.

appetite suppressants

Controlled Substance Schedule: IV

Indications

• Weight management as part of a program including caloric restriction and increased exercise in adults with an initial body mass index (BMI) of ≥30 kg/m²   or  a BMI of ≥27 kg/m²  with ≥1 other risk factor (hypertension, type 2 diabetes mellitus, or dyslipidemia).
• Weight management as part of a program including caloric restriction and increased exercise in children ≥12 yr old with an initial BMI in the 95th percentile or greater standardized for age and sex.

Action

• Phentermine:  ↓ appetite and food consumption;
• Topiramate:  ↓ appetite and enhances satiety.

Therapeutic Effect(s):

Weight loss.

Pharmacokinetics

Phentermine

Absorption: Extent of absorption following oral administration unknown.

Distribution: Unknown.

Metabolism and Excretion: Metabolized by the liver.

Half-life: 19–24 hr.

Topiramate

Absorption: 80% absorbed following oral administration.

Distribution: Unknown

Metabolism and Excretion: Not extensively metabolized. 70% excreted unchanged in urine.

Half-life: 21 hr.

TIME/ACTION PROFILE (weight loss)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity/idiosyncracy to sympathomimetics (contains tartrazine);
• Glaucoma;
• Hyperthyroidism;
• During/within 14 days of MAO inhibitors;
• End-stage renal disease on dialysis;
• Severe hepatic impairment;
• History of suicidal thought/active suicidal ideation;
• OB:  Pregnancy;
• Lactation: Lactation.

Use Cautiously in:

• Diabetes (weight loss may ↑ risk of hypoglycemia);
• History of substance abuse;
• Ketogenic diet (↑ risk of kidney stones);
• Rep:  Women of reproductive potential;
• Pedi:  Children <12 yr (safety and effectiveness not established); may ↓ vertical growth;
• Geri:  ↑ risk of adverse effects in older adults (consider age-related ↓ in cardiac, renal, and hepatic function; concurrent chronic disease states; and medications).

Adverse Reactions/Side Effects

CV: tachycardia, hypotension, palpitations

Derm: alopecia, ERYTHEMA MULTIFORME, oligohydrosis (↓ sweating), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: acute myopia, blurred vision, eye pain, secondary angle closure glaucoma, visual field defects

Endo: hypoglycemia

F and E: hypokalemia, metabolic acidosis

GI: altered taste, constipation, dry mouth, HEPATOTOXICITY

GU: ↑ serum creatinine, kidney stones

Metabolic: ↓ growth (children)

Neuro: headache, insomnia, paresthesia, cognitive impairment, dizziness, mood disorders, SEIZURES (FOLLOWING ABRUPT DISCONTINUATION), SUICIDAL IDEATION

Misc: ALLERGIC REACTION, hyperthermia

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• ↑ risk of hypokalemia with  non-potassium-sparing diuretics.
• ↑ risk of CNS depression with  other CNS depressants, including  alcohol, some  antihistamines,  sedative/hypnotics,  antipsychotics, and  opioid analgesics ; avoid concurrent use of alcohol.
• Altered exposure to  oral contraceptives  may ↑ risk of irregular bleeding.
•  Carbamazepine  or  phenytoin  may ↓ levels.
• Concurrent use of topiramate with  valproic acid  may ↑ risk of hyperammonemia.
• Concurrent use of topiramate with  carbonic anhydrase inhibitors  may ↑ risk of metabolic acidosis and kidney stones.
• ↑ risk of hypotension with  antihypertensive  and  diuretics.
• May ↓  pioglitazone  levels.

Route/Dosage

PO (Adults): Phentermine 3.75 mg/topiramate 23 mg once daily for 14 days; then ↑ to phentermine 7.5 mg/topiramate 46 mg once daily for 12 wk; then assess weight loss. If patient has not lost at least 3% of baseline body weight, ↑ dose to phentermine 11.25 mg/topiramate 69 mg once daily for 14 days; then phentermine 15 mg/topiramate 92 mg once daily for 12 wk; then assess weight loss. If patient has not lost ≥5% of baseline body weight, discontinue therapy, as success is unlikely. Discontinuation should proceed by taking the phentermine 15 mg/topiramate 92 mg capsule every other day for 1 wk and then discontinue therapy.

PO (Children ≥12 yr): Phentermine 3.75 mg/topiramate 23 mg once daily for 14 days; then ↑ to phentermine 7.5 mg/topiramate 46 mg once daily for 12 wk; then assess BMI. If patient has not experienced a reduction of ≥3% of baseline BMI, ↑ dose to phentermine 11.25 mg/topiramate 69 mg once daily for 14 days; then phentermine 15 mg/topiramate 92 mg once daily for 12 wk; then assess BMI. If patient has not experienced a ↓ of ≥5% of baseline BMI, discontinue therapy, as success is unlikely. Discontinuation should proceed by taking the phentermine 15 mg/topiramate 92 mg capsule every other day for 1 wk and then discontinue therapy. If weight loss exceeds 2 lb/wk, consider ↓ dose.

Renal Impairment 
PO (Adults and Children ≥12 yr): CCr <50 mL/min:  Not to exceed phentermine 7.5 mg/topiramate 46 mg once daily.

Hepatic Impairment 
PO (Adults and Children): Moderate hepatic impairment:  Not to exceed phentermine 7.5 mg/topiramate 46 mg once daily.

Availability (generic available)

Capsules (contain tartrazine): phentermine 3.75 mg (immediate-release [IR])/topiramate 23 mg (extended-release [ER]) (for titration only), phentermine 7.5 mg (IR)/topiramate 46 mg (ER), phentermine 11.25 mg (IR)/topiramate 69 mg (ER) (for titration only), phentermine 15 mg (IR)/topiramate 92 mg (ER)

Assessment

• Monitor patients for weight loss and adjust concurrent medications (antihypertensives, antidiabetics, lipid-lowering agents) as needed. Evaluate weight loss after each 12 wk of therapy.
• Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression. Discontinue therapy if these occur.
• Monitor BP and HR periodically during therapy; may cause ↑ in resting HR. May cause hypotension in patients treated with antihypertensives.

Lab Test Considerations:

Verify negative pregnancy test prior to starting therapy and monthly during therapy.

• Before starting and periodically during therapy, obtain a blood chemistry profile in all patients and blood glucose in patients with diabetes on antidiabetic medication.
• May cause hypoglycemia; monitor blood glucose closely in patients with diabetes.
• May cause metabolic acidosis; monitor serum bicarbonate prior to starting and periodically during therapy.
• May cause ↑ serum creatinine; peak ↑ observed after 4–8 wk of therapy. Monitor serum creatinine prior to and periodically during therapy; if persistent ↑ occur, ↓ dose or discontinue therapy.
• May cause hypokalemia; monitor serum potassium periodically during therapy.

Implementation

•  REMS: Because of teratogenic risk,  Qsymia  is only available through certified pharmacies that are enrolled in the Qsymia certified pharmacy network. Information can be obtained at www.QsymiaREMS.com or by calling 1-888-998-4887.
• PO Administer once daily in the morning without regard to food. Avoid dosing in the evening; may cause insomnia.

Patient/Family Teaching

• Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy. Instruct patient to take as directed. Do not stop taking without consulting health care professional. Discontinue gradually, taking one dose every other day for ≥1 wk before stopping to prevent seizures.  REMS: Explain  Qsymia  REMS requirements to patient.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Advise patient to avoid taking other CNS depressants, opioids, or alcohol.
• Advise patient to notify health care professional if sustained periods of heart pounding or racing while at rest; severe and persistent eye pain or significant changes in vision; changes in attention, concentration, memory, or difficulty finding words; or factors that can ↑ risk of acidosis (prolonged diarrhea, surgery, high-protein/low-carbohydrate diet, concomitant medications) occur.
• Inform patients and families of risk of suicidal thoughts and behavior (behavioral changes; emerging or worsening signs and symptoms of depression; unusual changes in mood; or emergence of suicidal thoughts, behavior, or thoughts of self-harm). Advise that these should be reported to health care professional immediately.
• May cause changes in mental performance, motor performance, or vision. Caution patients to avoid driving and other activities requiring alertness until response to medication is known.
• Instruct patient to ↑ fluid intake to ↑ urinary output and ↓ risk of kidney stones.
• Advise patient to monitor for ↓ sweating and ↑ body temperature during physical activity, especially in hot weather.
• Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during therapy. Advise female patients to notify health care professional if pregnancy is planned or suspected. For patients taking combined oral contraceptives, may cause irregular bleeding and spotting; advise patient to continue oral contraceptive and notify health care professional if spotting is concerning.

Evaluation/Desired Outcomes

Decrease in weight and BMI.