Dosing and uses of Qsymia (phentermine/topiramate)
Adult dosage forms and strengths
phentermine/topiramate (combination of immediate-release phentermine and extended-release topiramate)
capsule: Schedule IV
- 3.75mg/23mg
- 7.5mg/46mg
- 11.25mg/69mg
- 15mg/92mg
Obesity
Indicated as an adjunct to a reduced-calorie diet and exercise for chronic weight management in adults with an initial BMI ≥30 kg/m² (obese), or BMI ≥27 kg/m² (overweight) in the presence of at least 1 weight related comorbidity (eg, hypertension, type 2 diabetes mellitus, dyslipidemia)
Initial: 3.75 mg/23 mg PO qDay for 14 days, THEn
Day 15: Increase to 7.5 mg/46 mg PO qDay for 12 weeks, then evaluate weight loss
If a patient has not lost at least 3% of baseline body weight on 7.5 mg/46 mg, discontinue or escalate dose, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss at the 7.5 mg/46 mg dose
To escalate the dose: Increase to 11.25 mg/69 mg PO qDay for 14 days; followed by dosing 15 mg/92 mg qDay; evaluate weight loss following dose escalation to 15 mg/92 mg after an additional 12 weeks of treatment
If a patient has not lost at least 5% of baseline body weight on 15 mg/92 mg, discontinue as directed (ie, gradually), as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment
Note: 3.75 mg/23 mg and 11.25 mg/69 mg dosage strengths are for titration purposes only
Administration
Take once daily in the morning with or without food
Avoid dosing in the evening due to the possibility of insomnia
Discontinue 15 mg/92 mg gradually by taking a dose every other day for at least 1 week prior to stopping treatment altogether, due to the possibility of precipitating a seizure
Renal & Hepatic Impairment
Renal impairment
- Mild (≥50 mL/min): No dose adjustment required
- Moderate (30-49 mL/min) and severe (<30 mL/min): Not to exceed 7.5 mg/46 mg qDay
Hepatic impairment
- Mild (Child-Pugh 5-6): No dose adjustment required
- Moderate (Child-Pugh 7-9): Not to exceed 7.5 mg/46 mg qDay
- Severe (Child-Pugh 10-15): Avoid use
Pediatric dosage forms and strengths
Safety and efficacy not established
Qsymia (phentermine/topiramate) adverse (side) effects
>10%
Paresthesia (4.2-19.9%)
Dry mouth (6.7-19.1%)
Constipation (7.9-16.1%)
URI (12.2-15.8%)
Metabolic acidosis (6.4-12.8%)
Nasopharyngitis (9.4-12.5%)
Headache (7-10.6%)
1-10%
Insomnia (5-9.4%)
Dysgeusia (1.3-9.4%)
Dizziness (2.9-8.6%)
Increased serum creatinine (2.1-8.4%)
Sinusitis (6.8-7.8%)
Nausea (3.6-7.2%)
Bronchitis (4.4-6.7%)
Back pain (5.4-6.6%)
Diarrhea (5-6.4%)
Blurred vision (4-6.3%)
Fatigue (4.4-5.9%)
UTI (3.3-5.2%)
Hypokalemia (persistent) (0.4-4.9%)
Cough (3.3-4.8%)
Depression (2.8-4.3%)
Anxiety (1.8-4.1%)
Irritability (1.7-3.7%)
Alopecia (1.7-3.7%)
Hypoesthesia (0.8-3.7%)
Disturbance in attention (0.4-3.5%)
GERD (0.8-3.2%)
Extremity pain (2.1-3%)
Musculoskeletal pain (0.8-3%)
Muscle spasms (2.8-2.9%)
Dyspepsia (2.1-2.8%)
Sinus congestion (2-2.6%)
Rash (1.7-2.6%)
Pharyngeal pain (1.2-2.5%)
Dry eye (0.8-2.5%)
Gastroenteritis (0.8-2.5%)
Hypokalemia (acute) (0.4-2.5%)
Palpitations (0.8-2.4%)
Eye pain (2.1-2.2%)
Neck pain (1.2-2.2%)
Oral paresthesia (0.2-2.2%)
Decreased appetite (1.5-2.1%)
Nephrolithiasis (0.2-1.2%)
Dysmenorrhea (0.4-2.1%)
Chest discomfort (0.2-2.1%)
Thirst (1.8-2%)
Nasal congestion (1.2-2%)
Postmarketing Reports
Phentermine
- Allergic: Urticaria
- Cardiovascular: Increased blood pressure, ischemic events
- CNS: Euphoria, psychosis, tremor
- Reproductive: Changes in libido, impotence
Topiramate
- Central nervous system: Suicidal behavior and ideation
- Dermatologic: Bullous skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), pemphigus
- Gastrointestinal: Pancreatitis
- Hepatic: Hepatic failure (including fatalities), hepatitis
- Metabolic: Hyperammonemia, hypothermia
- Ophthalmic: Maculopathy, angle closure glaucoma, increased intraocular pressure
Warnings
Contraindications
Hypersensitivity or idiosyncrasy to sympathomimetic amines
Pregnancy
Glaucoma
Hyperthyroidism
Use of phentermine is contraindicated during or within 14 days following MAOIs due to risk for hypertensive crisis
Cautions
May cause fetal harm (see Contraindications; see Pregnancy and lactation)
May increase resting heart rate up to 20 bpm; caution in patients with history of cardiac or cerebrovascular disease
Antiepileptic drugs (AEDs), including topiramate, increase the risk of suicidal thoughts or behavior
Acute myopia associated with secondary angle closure glaucoma has been reported with topiramate; monitor for increased IOP due to risk of permanent loss of vision
May cause mood disorders, including depression, and anxiety, as well as insomnia; patient with history of depression may be at increased risk of recurrent depression or other mood disorders
Cognitive dysfunction (eg, impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties) reported; rapid titration or high initial doses may be associated with higher rates
Hyperchloremic, nonanion gap, and metabolic acidosis reported
Increased serum creatinine reported; peak increases were observed after 4-8 weeks of treatment and gradually declined but remained elevated over baseline values
Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues; monitor for needed diabetic therapy adjustments
In patients treated for hypertension, weight loss may increase the risk of hypotension; monitor for needed antihypertensive dose adjustments
Coadministration with alcohol or CNS depressants drugs with phentermine or topiramate may potentiate CNS depression or other centrally mediated effects of these agents (eg, dizziness, cognitive adverse reactions, drowsiness, light-headedness, impaired coordination, somnolence)
Abrupt withdrawal of topiramate associated with seizures in individuals without a history of seizures or epilepsy; gradually discontinue if taking 15 mg/92 mg
Caution with renal or hepatic impairment and adjust dose (see Renal & Hepatic Impairment)
Kidney stone formation reported; topiramate inhibits carbonic anhydrase activity and promotes kidney stone formation by reducing urinary citrate excretion and increasing urine pH; avoid coadministration with other carbonic anhydrase inhibitors; use in patients on a ketogenic diet may also increase this risk; increase fluid intake to decrease risk
Oligohidrosis (resulting in hyperthermia) reported with topiramate
Can cause changes in laboratory values; can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity; caution with coadministration of drug that cause hypokalemia (eg, furosemide, hydrochlorothiazide)
Obtain blood chemistry profile that includes bicarbonate, creatinine, potassium, and glucose at baseline and periodically during treatment
Use with combination oral contraceptives may increase frequency of irregular bleeding/spotting; need not discontinue unless spotting is trouble to patient
Consider dose reduction in patients with hepatic impairment; use with caution
Pregnancy and lactation
Pregnancy category: X
Can cause fetal harm and weight loss offers no potential benefit to a pregnant woman
Available epidemiologic data indicate an increased risk in oral clefts of 9.6% (cleft lip with or without cleft palate) with first trimester exposure to topiramate (NAAED Pregnancy Registry)
The effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus??? ability to tolerate labor
Qsymia Pregnancy Surveillance Program to monitor maternal-fetal outcomes of pregnancies that occur during therapy 1-888-998-4887
Lactation: Distributed in breast milk; because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Qsymia (phentermine/topiramate)
Mechanism of action
Phentermine: Sympathomimetic amine; induces anorectic effect via release of norepinephrine in the hypothalamus causing appetite suppression by increasing blood leptin concentration; exact mechanism of action unknown
Topiramate: Effect may be through appetite suppression and satiety enhancement that is induced by a combination of pharmacologic effects including augmenting neurotransmitter gamma-aminobutyrate activity, voltage-gated ion channels modulation, AMPA/kainite excitatory glutamate receptor inhibition, or carbonic anhydrase inhibition
Absorption
Phentermine (15 mg dose)
- Peak Plasma Time: 6 hr
- Peak Plasma Concentration: 49.1 ng/mL
- AUC: 1990-2000 ng???hr/mL
Topiramate (92 mg dose)
- Peak Plasma Time: 9 hr
- Peak Plasma Concentration: 1020 ng/mL
- AUC: 61,600-68,000 ng???hr/mL
Distribution
Phentermine
- Protein Bound: 17.5%
- Vd: 348 L
Topiramate
- Protein Bound: 15-41%
- Vd: 50.8 L (central compartment); 13.1 L (peripheral compartment)
Metabolism
Phentermine
- Metabolized by 2 metabolic pathways, p-hydroxylation on the aromatic ring and N-oxidation on the aliphatic side chain
- CYP3A4 primarily metabolizes phentermine but does not show extensive metabolism
- Monoamine oxidase (MAO)-A and MAO-B do not metabolize phentermine
Topiramate
- Not extensively metabolized
Elimination
Phentermine
- Half-life: 20 hr (terminal)
- Clearance: 8.79 L/hr
- Excretion: 70-80% urine (as unchanged drug)
Topiramate
- Half-life: 65 hr (terminal)
- Clearance: 1.17 L/hr
- Excretion: 70% urine (as unchanged drug)
