Phentermine and Topiramate (Monograph)

Drug class: Anorexigenic Agents, Miscellaneous
Chemical name: 2-methyl-1-phenylpropan-2-amine
Molecular formula: C₁₀H₁₅NC₁₂H₂₁NO₈S
CAS number: 1197-21-3

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for the fixed combination of phentermine and topiramate (phentermine/topiramate; Qsymia) to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of phentermine/topiramate and consists of the following: elements to assure safe use and implementation system. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Anorexigenic agent; fixed combination containing phentermine (sympathomimetic amine) and topiramate (anticonvulsant agent).

Uses for Phentermine and Topiramate

Chronic Weight Management

Adjunct to caloric restriction and increased physical activity for chronic weight management; appropriate candidates for therapy include obese adults with pretreatment BMI ≥30 kg/m² or overweight adults with pretreatment BMI ≥27 kg/m² who have at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia.

Effects on cardiovascular morbidity and mortality not established.

Safety and efficacy in combination with other products used to promote weight loss, including prescription drugs, nonprescription (OTC) drugs, and herbal preparations, not established.

Clinical practice guidelines recommend treatment for obesity in patients with excess body weight and associated health risks. Initiate comprehensive lifestyle intervention; may consider adjunctive pharmacologic therapy in patients who fail to achieve or sustain clinically meaningful weight loss (generally defined as loss of >4–5% of total body weight) with behavioral modification alone. Evaluate response to drug therapy after 3–4 months; if clinically meaningful weight loss not achieved, consider new treatment plan.

Phentermine and Topiramate Dosage and Administration

General

Withdraw gradually to minimize potential for seizures. (See Discontinuance of Therapy under Cautions.)
Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression. (See Suicidality Risk under Cautions.)

Restricted Distribution

Available only through a limited distribution program under the Qsymia REMS. Only certified pharmacies may distribute the drug. Additional information is available at www.qsymiaREMS.com or 1-888-998-4887.

Administration

Oral Administration

Administer orally as extended-release capsules once daily in the morning with or without food. (See Food under Pharmacokinetics.) Do not administer in the evening to avoid insomnia.

Dosage

Available as extended-release capsules containing immediate-release phentermine hydrochloride and extended-release topiramate in various fixed-dose combinations. Dosage is expressed in terms of dose of phentermine and dose of topiramate.

Adults

Chronic Weight Management

Oral

Initially, 1 capsule (phentermine 3.75 mg/topiramate 23 mg) once daily for 14 days, then increase to recommended dosage of phentermine 7.5 mg/topiramate 46 mg once daily.

Evaluate response after 12 weeks of treatment at a dosage of phentermine 7.5 mg/topiramate 46 mg once daily; if a ≥3% weight loss not achieved, discontinue drug or increase dosage. If a decision is made to escalate dosage, increase to phentermine 11.25 mg/topiramate 69 mg once daily for 14 days, and then to phentermine 15 mg/topiramate 92 mg once daily.

Evaluate response after 12 weeks of treatment at a dosage of phentermine 15 mg/topiramate 92 mg once daily; if a ≥5% weight loss not achieved, discontinue drug as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

Discontinue therapy gradually to prevent precipitation of seizures. In patients receiving a dosage of phentermine 15 mg/topiramate 92 mg once daily, discontinue treatment by taking 1 dose every other day for at least 1 week prior to withdrawing therapy.

Prescribing Limits

Adults

Chronic Weight Management

Oral

Maximum recommended dosage is phentermine 15 mg/topiramate 92 mg once daily.

Special Populations

Hepatic Impairment

In patients with moderate hepatic impairment, do not exceed dosage of phentermine 7.5 mg/topiramate 46 mg once daily. Avoid use in patients with severe hepatic impairment. (See Hepatic Impairment under Cautions.)

Renal Impairment

No dosage adjustment necessary in patients with mild renal impairment.

In patients with moderate (Cl_cr 30–50 mL/minute) or severe (Cl_cr <30 mL/minute) renal impairment, do not exceed dosage of phentermine 7.5 mg/topiramate 46 mg once daily. (See Renal Impairment under Cautions.)

Geriatric Patients

In general, select dosage cautiously, usually starting at the low end of the dosing range.

Cautions for Phentermine and Topiramate

Contraindications

Pregnancy.
Glaucoma.
Hyperthyroidism.
Administration during or within 14 days of taking an MAO inhibitor.
Known hypersensitivity or idiosyncrasy to sympathomimetic amines.

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

Risk of fetal harm. In utero exposure to topiramate (during first trimester of pregnancy) associated with increased risk of oral cleft birth defects. Developmental toxicity (e.g., teratogenicity, embryotoxicity) demonstrated with topiramate in multiple species of animals. In animal reproduction studies using phentermine/topiramate, reduced fetal body weight, reduced maternal weight gain, and structural malformations consistent with those observed with topiramate alone reported.

If phentermine/topiramate is used during pregnancy or if a patient becomes pregnant while taking the fixed combination, discontinue treatment immediately and apprise patient of the potential fetal hazard.

In females of reproductive potential, obtain a negative pregnancy test prior to initiating therapy and monthly thereafter while receiving the fixed combination; such patients should use effective contraception during therapy.

Increased Heart Rate

Potential for increased heart rate. In clinical studies, increased heart rate reported in more patients receiving phentermine/topiramate than placebo; however, clinical importance not known, particularly in patients with cardiovascular or cerebrovascular disease (e.g., those with history of MI or stroke in previous 6 months, life-threatening arrhythmias, or CHF).

Measure resting heart rate on a regular basis, especially in patients with cardiovascular or cerebrovascular disease or when initiating therapy or increasing dosage. (See Advice to Patients.)

In patients who experience a sustained increase in resting heart rate during phentermine/topiramate therapy, reduce dosage or discontinue drug.

Not studied in patients with recent or unstable cardiovascular or cerebrovascular disease; therefore, not recommended in such patients.

Suicidality Risk

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants, including topiramate; risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%). Increased suicidality risk was observed as early as 1 week after initiation of anticonvulsant therapy; because most studies were ≤24 weeks' duration, risk of treatment beyond 24 weeks not known. Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.

Monitor closely for emergence or worsening of suicidal thoughts and behavior. If any such symptoms develop, discontinue therapy. Avoid use in patients with a history of suicide attempts or active suicidal ideation. (See Advice to Patients.)

Acute Myopia and Secondary Angle Closure Glaucoma

Acute myopia associated with secondary angle closure glaucoma reported in patients receiving topiramate. Typically occurs within 1 month of initiating topiramate therapy. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings may include myopia, anterior chamber shallowing, ocular hyperemia (redness), and increased intraocular pressure; mydriasis may or may not be present.

If any such symptoms occur, immediately discontinue drug. Elevated intraocular pressure of any etiology, if left untreated, can lead to serious adverse events including permanent loss of vision.

Mood and Sleep Disorders

Mood disorders (e.g., depression, anxiety, insomnia) reported. Patients with a history of depression may be at increased risk of recurrent depression or other mood disorders while receiving the drug. In most cases, symptoms resolved spontaneously or following drug discontinuance.

If clinically important or persistent symptoms occur, consider dosage reduction or discontinuance of therapy. Discontinue therapy in patients who exhibit symptoms of suicidal ideation or behavior.

CNS/Cognitive Effects

Cognitive dysfunction (e.g., impairment of concentration, attention, memory, speech, or language) may occur. Risk is increased with rapid titration or use of high initial dosages.

If cognitive dysfunction persists, consider dosage reduction or discontinuance of therapy.

Concomitant use with alcohol or CNS depressant drugs (e.g., barbiturates, benzodiazepines, hypnotic agents) may potentiate CNS depression or other centrally mediated effects of these agents (e.g., dizziness, adverse cognitive reactions, drowsiness, lightheadedness, impaired coordination, somnolence). Avoid concomitant use of alcohol.

Metabolic Acidosis

Hyperchloremic, non-anion gap metabolic acidosis reported. Risk may be increased in patients with predisposing factors (e.g., renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, ketogenic diet).

Manifestations of acute or chronic metabolic acidosis may include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe complications including cardiac arrhythmias or stupor. Chronic, untreated metabolic acidosis may result in potentially serious sequelae (e.g., nephrolithiasis or nephrocalcinosis, osteomalacia and/or osteoporosis with risk of fractures).

Concomitant use of carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide, dichlorphenamide) may increase severity of metabolic acidosis. (See Specific Drugs under Interactions.)

Measure serum bicarbonate concentrations prior to and during therapy. In clinical studies, serum bicarbonate concentrations were maximally reduced at 4 weeks and normalized by 56 weeks without any change in therapy. If persistent metabolic acidosis develops, manufacturer states to reduce dosage or discontinue phentermine/topiramate.

Renal Effects

Increased serum creatinine concentrations reported. In clinical studies, peak increases were observed after 4–8 weeks of treatment and generally declined over time. However, effect of chronic treatment on renal function not known.

Measure serum creatinine concentrations prior to and during therapy. If persistent elevations in serum creatinine concentrations occur, reduce dosage or discontinue phentermine/topiramate.

Hypoglycemia in Patients with Type 2 Diabetes Mellitus

Weight loss may increase risk of hypoglycemia in patients with type 2 diabetes mellitus receiving treatment with insulin and/or insulin secretagogues (e.g., sulfonylureas). Phentermine/topiramate has not been studied in combination with insulin.

Measure blood glucose concentrations prior to and during therapy in patients with type 2 diabetes mellitus. To minimize risk of hypoglycemia, consider reducing dosages of non-glucose-dependent antidiabetic agents. If hypoglycemia develops after initiating phentermine/topiramate, adjust patient's antidiabetic regimen accordingly.

Hypotension in Patients Receiving Antihypertensive Agents

Weight loss may increase risk of hypotension in patients receiving antihypertensive agents.

Measure BP prior to and during therapy in such patients. If symptoms of hypotension (e.g., dizziness, lightheadedness, syncope) occur, adjust patient's antihypertensive regimen appropriately.

Discontinuance of Therapy

Abrupt withdrawal of topiramate may precipitate seizures. If immediate discontinuance of phentermine/topiramate is medically necessary, monitor patient.

In patients discontinuing therapy from maximum dosage of phentermine 15 mg/topiramate 92 mg, gradually taper dosage as recommended to reduce risk of seizures. (See Dosage under Dosage and Administration.)

Kidney Stones

Risk of kidney stone formation. Topiramate is a carbonic anhydrase inhibitor; may promote stone formation by reducing urinary citrate excretion and increasing urinary pH. Ketogenic diet or concomitant use of carbonic anhydrase inhibitors may increase risk. (See Specific Drugs under Interactions.)

Instruct patients to increase fluid intake. (See Advice to Patients.)

Oligohidrosis and Hyperthermia

Oligohidrosis, sometimes resulting in hospitalization, reported with topiramate. Manifestations included decreased sweating and elevated body temperature. Some cases occurred with use of topiramate after exposure to elevated environmental temperatures.

Advise patients to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather. Use caution when phentermine/topiramate is administered with other drugs that can also predispose patients to heat-related disorders (e.g., other carbonic anhydrase inhibitors, drugs with anticholinergic activity).

Hypokalemia

Risk of hypokalemia because of potential for topiramate to inhibit carbonic anhydrase. Concomitant use with non-potassium sparing diuretics may increase risk. (See Specific Drugs under Interactions.)

Monitor patients for hypokalemia.

Laboratory Monitoring

Changes in several laboratory parameters reported in clinical studies. Obtain a blood chemistry profile, including bicarbonate, creatinine, potassium, and glucose concentrations, at baseline and periodically during treatment.

Abuse Potential and Dependence

Phentermine/topiramate is subject to control as a schedule IV (C-IV) drug. Phentermine is chemically and pharmacologically similar to amphetamines, which have been extensively abused for their CNS stimulant effects. Consider potential for abuse of phentermine when determining whether to use phentermine/topiramate as part of a weight reduction program.

Potential for phentermine/topiramate to cause physical dependence not systematically evaluated. Limited information available on dependence potential of the individual components. Abrupt discontinuance of topiramate associated with seizures in patients without a history of seizures or epilepsy. Abrupt discontinuance of phentermine following prolonged high-dosage administration resulted in extreme fatigue, depression, and sleep EEG changes. If rapid withdrawal of phentermine/topiramate is required, appropriately monitor patient.

Specific Populations

Pregnancy

Contraindicated in pregnancy. May cause fetal harm and offers no potential benefit to a pregnant woman. If a patient becomes pregnant, discontinue drug immediately and apprise patient of the potential fetal hazard.

In women of childbearing potential, perform pregnancy test prior to initiating therapy and monthly thereafter. Advise such women to use effective contraception during therapy.

A Pregnancy Surveillance Program has been established. Encourage women who become pregnant while receiving the drug to call the program at 888-998-4887.

Effect of topiramate-induced metabolic acidosis not specifically studied during pregnancy; however, metabolic acidosis during pregnancy is known to cause decreased fetal growth, decreased fetal oxygenation, and fetal death.

Lactation

Phentermine/topiramate may be distributed into human milk. Discontinue nursing or drug.

Pediatric Use

Safety and efficacy not established; use not recommended. Serious adverse reactions including acute angle glaucoma, oligohidrosis and hyperthermia, metabolic acidosis, cognitive and neuropsychiatric reactions, hyperammonemia and encephalopathy, and kidney stones, reported in pediatric patients receiving topiramate.

Geriatric Use

In clinical trials, only a limited number (7%) of patients were ≥65 years of age; no overall differences in safety or effectiveness observed between these patients and younger adults, but greater sensitivity of some older individuals cannot be ruled out.

Insufficient experience in patients ≥65 years of age to determine whether they respond differently from younger patients. In general, select dosage carefully in geriatric patients, 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.

Hepatic Impairment

In patients with mild (Child-Pugh score 5–6) or moderate (Child-Pugh score 7–9) hepatic impairment, exposure of phentermine may be increased. Adjust dosage of phentermine/topiramate in patients with moderate hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

Not studied in patients with severe hepatic impairment (Child-Pugh score 10–15); avoid use.

Renal Impairment

Both phentermine and topiramate are eliminated by renal excretion. Therefore, exposure to the drugs may be increased in patients with renal impairment. Adjust dosage in patients with moderate or severe renal impairment. (See Renal Impairment under Dosage and Administration.)

Not studied in patients with end-stage renal disease on dialysis; avoid use.

Common Adverse Effects

Paresthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth.

Drug Interactions

Phentermine does not inhibit CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 and does not induce CYP1A2, 2B6, or 3A4. Phentermine is not a substrate of P-glycoprotein (P-gp).

Topiramate is a mild inhibitor of CYP2C19, but does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1, or 3A4/5. Topiramate is a mild inducer of CYP3A4. Topiramate is not a substrate of P-gp.

Specific Drugs

Drug	Interaction	Comments
Amitriptyline	Increased plasma amitriptyline concentrations	Adjust amitriptyline dosage based on clinical response
Anticholinergic agents	Possible increased risk of hyperthermia	Use concomitantly with caution
Carbamazepine	Clinically important decreases in plasma concentrations of topiramate observed; plasma concentrations of carbamazepine or its active metabolite not substantially altered
Carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide, zonisamide)	Possible increased risk or severity of metabolic acidosis and kidney stone formation; possible increased risk of hyperthermia	Avoid concomitant use If used concomitantly in patients with predisposing risk factors for metabolic acidosis, monitor for onset or worsening of this condition
CNS depressants (alcohol, barbiturates, benzodiazepines, hypnotics)	May potentiate CNS depression or other CNS effects (e.g., dizziness, drowsiness, impaired coordination, somnolence)	Avoid concomitant use of alcohol
Digoxin	Serum digoxin AUC was decreased by 12% in one study; however, clinical importance not known
Dihydroergotamine	Pharmacokinetics of both drugs not affected
Diltiazem	Decreased peak plasma concentrations and AUC of diltiazem by 10 and 25%, respectively; systemic exposure to desacetyl diltiazem also decreased, but no effect on N-desmethyl diltiazem Increased peak plasma concentrations and AUC of topiramate by 16 and 19%, respectively
Glyburide	Concomitant administration in patients with type 2 diabetes mellitus decreased peak plasma concentrations and AUC of glyburide by 22 and 25%, respectively; systemic exposure of the active metabolites, 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide, also were reduced Pharmacokinetics of topiramate not affected
Haloperidol	Pharmacokinetics of haloperidol not affected
Hydrochlorothiazide	Peak plasma concentrations and AUC of topiramate increased by 27 and 29%, respectively; pharmacokinetics of hydrochlorothiazide not substantially altered Non-potassium sparing diuretics such as hydrochlorothiazide may potentiate hypokalemia	Monitor patients for hypokalemia; measure potassium concentrations prior to and during treatment
Lamotrigine	Plasma concentrations of lamotrigine were altered by <10% and plasma topiramate concentrations were decreased by 13%
Lithium	Pharmacokinetics of lithium not affected during concurrent administration of topiramate 200 mg daily, but peak plasma concentrations and AUC of lithium increased by 27 and 26%, respectively, during concurrent administration of topiramate dosages up to 600 mg daily	Monitor serum lithium concentrations in patients receiving concurrent high-dose topiramate therapy
Loop diuretics (e.g., furosemide)	Non-potassium sparing diuretics such as loop diuretics may potentiate hypokalemia	Monitor patients for hypokalemia; measure potassium concentrations prior to and during treatment
MAO inhibitors	Risk of hypertensive crisis	Concomitant use during and within 14 days following administration of MAO inhibitor contraindicated
Metformin	Increased peak plasma concentrations and AUC of metformin by 16 and 23%, respectively; pharmacokinetics of phentermine/topiramate altered to only a slight extent
Oral contraceptives	Systemic exposure of ethinyl estradiol decreased by 16% and exposure of norethindrone increased by 16% Effect on contraceptive efficacy not evaluated	Increased risk of pregnancy not anticipated; however, irregular bleeding may occur as a result of altered concentrations of the estrogen and progestin components Advise patients to not discontinue oral contraceptives if spotting occurs, but to notify clinician if spotting is troublesome
Phenobarbital	Altered plasma concentrations of phenobarbital by <10%
Phenytoin	Clinically important decreases in plasma topiramate concentrations observed; possible increase in serum phenytoin concentrations (generally in those receiving twice-daily phenytoin regimen)
Pioglitazone	Decreased systemic exposure to pioglitazone and its active metabolites observed; however, clinical importance not known	Monitor patients for adequate glycemic control when pioglitazone is added to phentermine/topiramate therapy or vice versa
Primidone	Altered plasma concentrations of primidone by <10%
Propranolol	Pharmacokinetics of either drug not affected
Risperidone	No clinically important changes in systemic exposure of risperidone plus 9-hydroxyrisperidone or topiramate; therefore, interaction not likely to be clinically important
Sitagliptin	Pharmacokinetics of both drugs unaffected
Sumatriptan	No effects on pharmacokinetics of sumatriptan
Valproic acid	Decreased topiramate plasma concentrations by 14% and valproic acid plasma concentrations by 11% Concomitant use also associated with hyperammonemia with and without encephalopathy, and also with hypothermia (with and without hyperammonemia)	May be prudent to measure blood ammonia concentrations in patients who develop hypothermia or encephalopathy during concomitant therapy
Venlafaxine	Pharmacokinetics of venlafaxine, O-desmethylvenlafaxine, and topiramate not affected

Phentermine and Topiramate Pharmacokinetics

Absorption

Bioavailability

Following oral administration of fixed combination, peak plasma concentrations of phentermine and topiramate achieved in 6 and 9 hours, respectively.

Food

Pharmacokinetics of both phentermine and topiramate were not altered when administered with a high-fat meal.

Special Populations

In patients with mild (Child-Pugh score 5–6) or moderate (Child-Pugh score 7–9) hepatic impairment, exposure of phentermine may be increased.

Exposure to both phentermine and topiramate may be increased in patients with moderate (Cl_cr 30 to <50 mL/minute) or severe (Cl_cr <30 mL/minute) renal impairment.

Distribution

Plasma Protein Binding

Phentermine: 17.5%.

Topiramate: 15–41%.

Elimination

Metabolism

Phentermine: Minimally metabolized by CYP3A4.

Topiramate: Not extensively metabolized.

Elimination Route

Phentermine: Approximately 70–80% of an administered dose is eliminated in urine as unchanged drug.

Topiramate: Approximately 70% of an administered dose is found in urine as unchanged drug.

Half-life

Phentermine: Mean terminal half-life is about 20 hours.

Topiramate: Mean terminal half-life is about 65 hours.

Stability

Storage

Oral

Fixed-combination Capsules

15–25°C; keep container tightly closed and protect from moisture.

Actions

Exact mechanism of action not known.
Effects of phentermine are likely mediated by release of catecholamines in the hypothalamus, resulting in reduced appetite and decreased food consumption; other metabolic effects also may be involved.
Mechanism of topiramate may be due to its effects on appetite suppression and satiety enhancement induced by a combination of pharmacologic effects, including augmentation of GABA activity, modulation of voltage-gated ion channels, inhibition of AMPA/kainite excitatory glutamate receptors, and inhibition of carbonic anhydrase.

Advice to Patients

Importance of advising patients that phentermine/topiramate is indicated for chronic weight management in conjunction with a reduced-calorie diet and increased physical activity.
Importance of advising patients that phentermine/topiramate is only available through a network of certified pharmacies. Instruct patients on how to access the fixed-combination preparation through these pharmacies. Additional information may be obtained at www.QsymiaREMS.com or at 1-888-998-4887.
Importance of advising patients to take phentermine/topiramate as prescribed.
Risk of fetal harm. Advise patients to avoid getting pregnant while taking phentermine/topiramate and that pregnancy testing is recommended prior to initiating the fixed-combination preparation and monthly thereafter during therapy. Advise patients on effective methods of contraception, as well as the importance of using effective contraception consistently during phentermine/topiramate therapy. Advise females who become pregnant during phentermine/topiramate therapy to immediately discontinue the fixed combination and inform their clinician.
Risk of increased heart rate; importance of advising patients to inform their clinician if they experience sustained periods of heart pounding or racing while at rest.
Anticonvulsants, including topiramate, may increase the risk of suicidal thoughts or behavior. Importance of patients, caregivers, and family members being alert to and immediately reporting emergence or worsening of depression, any unusual changes in mood or behavior, or emergence of suicidal thoughts, behavior, or thoughts of self harm.
Risk of acute myopia and secondary angle closure glaucoma. Advise patients to report symptoms of severe and persistent eye pain or significant vision changes to their clinician.
Risk of CNS/cognitive effects such as dizziness, confusion, visual changes, and impaired concentration. Advise patients to inform their clinician if they experience any changes in attention, concentration, memory, and/or difficulty finding words. Advise patients not to drive or operate machinery until they have gained sufficient experience with the drug.
Risk of metabolic acidosis. Advise patients to inform their clinician about any factors that can increase the risk of acidosis (e.g., prolonged diarrhea, surgery, high protein/low carbohydrate diet, and/or concomitant medications such as carbonic anhydrase inhibitors).
Importance of informing patients that weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus who are being treated with insulin and/or insulin secretagogues (e.g., sulfonylureas). Advise patients with type 2 diabetes mellitus on antidiabetic therapy to monitor their blood glucose levels and report symptoms of hypoglycemia to their clinician.
Importance of advising patients that concomitant use of alcohol or CNS depressants (e.g., barbiturates, benzodiazepines, sleep medications) with phentermine/topiramate may potentiate CNS depression or other centrally-mediated effects of these agents such as dizziness, cognitive adverse reactions, drowsiness, lightheadedness, impaired coordination, and somnolence. Advise patients not to drink alcohol while taking phentermine/topiramate.
Importance of advising patients not to discontinue phentermine/topiramate therapy without consulting with their clinician. Abrupt withdrawal has been associated with seizures in patients without a history of seizures or epilepsy.
Risk of 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 clinician.
Importance of informing patients that oligohidrosis (decreased sweating) and elevations in body temperature above normal have been reported in association with the use of topiramate. Advise patients to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs or herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Phentermine hydrochloride/topiramate is subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

The fixed combination of phentermine and topiramate (phentermine/topiramate; Qsymia) is available only through a REMS program, the Qsymia REMS program, because of the teratogenic risk associated with phentermine/topiramate therapy. (See Restricted Distribution under Dosage and Administration.)

Phentermine Hydrochloride and Topiramate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	Phentermine Hydrochloride 3.75 mg (of phentermine; immediate-release) and Topiramate 23 mg (extended-release)	Qsymia (C-IV)	Vivus
		Phentermine Hydrochloride 7.5 mg (of phentermine; immediate-release) and Topiramate 46 mg (extended-release)	Qsymia (C-IV)	Vivus
		Phentermine Hydrochloride 11.25 mg (of phentermine; immediate-release) and Topiramate 69 mg (extended-release)	Qsymia (C-IV)	Vivus
		Phentermine Hydrochloride 15 mg (of phentermine; immediate-release) and Topiramate 92 mg (extended-release)	Qsymia (C-IV)	Vivus