phentermine/topiramate

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 patients with an initial body mass index (BMI) of ≥30 kg/m2  or a BMI of ≥27 kg/m2  with at least one other risk factor (hypertension, type 2 diabetes mellitus, or dyslipidemia).

Action

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

Therapeutic Effect(s):

Weight loss.

Pharmacokinetics

Absorption: Phentermine– Unknown;  Topiramate– 80% absorbed following oral administration.

Distribution: Phentermine– Unknown;  Topiramate– Unknown.

Metabolism and Excretion: Phentermine– metabolized by the liver;  Topiramate– 70% excreted unchanged in urine.

Half-life: Phentermine– 19–24 hr;  Topiramate– 21 hr.

TIME/ACTION PROFILE (phentermine–appetite suppression, topiramate–blood levels)

ROUTEONSETPEAKDURATION
PO (weight loss)within 8 wk16–32 wkunknown

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity/idiosyncracy to sympathomimetics;
  • Glaucoma;
  • Hyperthyroidism;
  • During/within 14 days of MAO inhibitors;
  • Severe renal impairment (CCr <30 mL/min);
  • Severe hepatic impairment;
  • History of suicidal thought/active suicidal ideation;
  • OB:  Pregnancy (may cause fetal harm);
  • Lactation: Lactation.

Use Cautiously in:

  • Diabetes (weight loss may ↑ risk of hypoglycemia);
  • History of substance abuse;
  • Rep:  Women of reproductive potential;
  • Pedi:  Safety and effectiveness not established in children;
  • 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: ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, alopecia, oligohydrosis (↓ sweating)

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

Endo: hypoglycemia

F and E: metabolic acidosis, hypokalemia

GI: HEPATOTOXICITY, altered taste, constipation, dry mouth

GU: ↑ serum creatinine, kidney stones

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

Misc: 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.
  • Blood levels of topiramate may be ↓ by  carbamazepine  or  phenytoin.
  • 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): Initial dose– one phentermine 3.75 mg/topiramate 23 mg capsule once daily for 14 days, then ↑ to one phentermine 7.5 mg/topiramate 46 mg capsule once daily for 12 wk, then assess weight loss. If weight loss has not exceeded 3% of baseline, discontinue or ↑ dose to one phentermine 11.25 mg/topiramate 69 mg capsule once daily for 14 days, then one phentermine 15 mg/topiramate 92 mg capsule once daily for 12 wk, if weight loss has not exceeded 5% of baseline, discontinue as success is unlikely. Discontinuation should proceed by taking the phentermine 15 mg/topiramate 92 mg capsule every other day for 1 wk.

Renal Impairment 
PO (Adults): CCr ≥30 mL/min–<50 mL/min– daily dose should not exceed one phentermine 7.5 mg/topiramate 46 mg capsule once daily.

Hepatic Impairment 
PO (Adults): Child-Pugh score 7–9– daily dose should not exceed one phentermine 7.5 mg/topiramate 46 mg capsule once daily.

Availability

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

Cost: 3.75 mg/23 mg $163.24/30, 7.5 mg/46 mg $184.49/30, 11.25 mg/69 mg $221.38/30, 15 mg/92 mg $239.40/30

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 phentermine/topiramate if these occur.

  • Monitor BP and heart rate periodically during therapy; may cause increase in resting heart rate. May cause hypotension in patients treated with antihypertensives.

Lab Test Considerations:

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

  • May cause hypoglycemia; monitor blood glucose closely in diabetic patients.
  • May cause metabolic acidosis; monitor serum bicarbonate, prior to starting and periodically during therapy.
  • May cause ↑ serum creatinine; peak increases observed after 4–8 wk of therapy. Monitor serum creatinine prior to and periodically during therapy; if persistent elevations occur, decrease dose or discontinue therapy.
  • May cause hypokalemia; monitor serum potassium periodically during therapy.

Implementation

  •  REMS: 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

  • Instruct patient to take phentermine/topiramate as directed. Do not stop taking without consulting health care professional. Discontinue gradually taking 1 dose every other day for at least 1 wk before stopping to prevent seizures.  REMS: Explain Qsymia REMS requirements to patient.
  • 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, and/or difficulty finding words; factors that can increase risk of acidosis (prolonged diarrhea, surgery, high-protein/low-carbohydrate diet, and/or concomitant medications).

  • 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, and/or vision. Caution patients to avoid driving and other activities requiring alertness until response to medication is known.
  • Instruct patient to increase fluid intake to increase urinary output and decrease risk of kidney stones.
  • Advise patient to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather.
  • 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.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breast feeding 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. If 3% of baseline body weight is not lost by Week 12, increase dose or discontinue phentermine/topiramate. Evaluate after second 12 wk of therapy. If 5% of baseline body weight is not lost by second 12 wk of therapy, as it is unlikely patient will achieve and sustain clinically meaningful weight loss with continued treatment.