Complete SPL Sections#
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Phentermine and topiramate extended-release capsules are indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adults and pediatric patients aged 12 years and older with obesity Adults with overweight in the presence of at least one weight-related comorbid condition Limitations of Use The effect of phentermine and topiramate extended-release capsules on cardiovascular morbidity and mortality has not been established. The safety and effectiveness of phentermine and topiramate extended-release capsules in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Phentermine and topiramate extended-release capsules are available in four strengths (phentermine mg/topiramate mg): 3.75 mg/23 mg - White opaque cap printed with WPI, orange opaque body printed with 2196 7.5 mg/46 mg - White opaque cap printed with WPI, green opaque body printed with 2195 11.25 mg/69 mg - Light yellow opaque cap printed with WPI, white opaque body printed with 2299 15 mg/92 mg - White opaque cap printed with WPI, dark scarlet opaque body printed with 2194
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Phentermine and topiramate extended-release capsules are contraindicated in patients: Who are pregnant [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] With glaucoma [see Warnings and Precautions ( 5.3 )] With hyperthyroidism Taking or within 14 days of stopping a monoamine oxidase inhibitors [see Drug Interactions ( 7 )] With known hypersensitivity to phentermine, topiramate or any of the excipients in phentermine and topiramate extended-release capsules, or idiosyncrasy to the sympathomimetic amines. Anaphylaxis and angioedema have occurred with topiramate [see Warnings and Precautions (5.15)] .
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
The following clinically significant adverse reactions are described elsewhere in the labeling: Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 , 8.6 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.2 )] Risk of Ophthalmologic Adverse Reactions [see Warnings and Precautions ( 5.3 )] Mood and Sleep Disorders [see Warnings and Precautions ( 5.4 )] Cognitive Impairment [see Warnings and Precautions ( 5.5 )] Slowing of Linear Growth [see Warnings and Precautions ( 5.6 )] Metabolic Acidosis [see Warnings and Precautions ( 5.7 )] Decrease in Renal Function [see Warnings and Precautions ( 5.8 )] Risk of Seizures with Abrupt Withdrawal of Phentermine and Topiramate Extended-Release Capsules [see Warnings and Precautions ( 5.9 )] Kidney Stones [see Warnings and Precautions ( 5.10 )] Oligohidrosis and Hyperthermia [see Warnings and Precautions ( 5.11 )] Hypokalemia [see Warnings and Precautions ( 5.12 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions ( 5.13 )] Serious Skin Reactions [see Warnings and Precautions ( 5.14 )] Anaphylaxis and Angioedema [see Warnings and Precautions ( 5.15 )]
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
Table 5 displays clinically significant drug interactions with phentermine and topiramate extended-release capsules. Table 5. Clinically Significant Drug Interactions with Phentermine and Topiramate Extended-Release Capsules Monoamine Oxidase Inhibitors Clinical Impact Concomitant use of phentermine with monoamine oxidase inhibitors (MAOIs) increases the risk of hypertensive crisis. Intervention Concomitant use of phentermine and topiramate extended-release capsules is contraindicated during MAOI treatment and within 14 days of stopping an MAOI. Oral Contraceptives Clinical Impact Coadministration of multiple-dose phentermine and topiramate extended-release capsules 15 mg/92 mg once daily with a single dose of oral contraceptive containing 35 mcg ethinyl estradiol (estrogen component) and 1 mg norethindrone (progestin component), in obese otherwise healthy volunteers, decreased the exposure of ethinyl estradiol by 16% and increased the exposure of norethindrone by 22% [see Clinical Pharmacology ( 12.3 )] . Although this interaction is not anticipated to increase the risk of pregnancy, irregular bleeding (spotting) may occur more frequently due to both the increased exposure to the progestin and lower exposure to the estrogen, which tends to stabilize the endometrium. Intervention Inform patients not to discontinue their combination oral contraceptive if spotting occurs, but to notify their health care provider if the spotting is troubling to them. CNS Depressants Including Alcohol Clinical Impact The concomitant use of alcohol or CNS depressant drugs (e.g., barbiturates, benzodiazepines, and sleep medications) with phentermine or topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Intervention Advise patients not to drive or operate machinery until they have gained sufficient experience on phentermine and topiramate extended-release capsules to gauge whether it adversely affects their mental performance, motor performance, and/or vision. Caution patients against excessive alcohol intake when taking phentermine and topiramate extended-release capsules. Consider phentermine and topiramate extended-release capsule dosage reduction or discontinuation if cognitive dysfunction persists [see Warnings and Precautions ( 5.5 )] . Non-Potassium Sparing Diuretics Clinical Impact Concurrent use of phentermine and topiramate extended-release capsules with non-potassium sparing diuretics may potentiate the potassium-wasting action of these diuretics. Concomitant administration of hydrochlorothiazide alone with topiramate alone has been shown to increase the C max and AUC of topiramate by 27% and 29%, respectively. Intervention When phentermine and topiramate extended-release capsules are used concomitantly with non-potassium-sparing diuretics, measure potassium before and during phentermine and topiramate extended-release capsule treatment [see Warnings and Precautions ( 5.12 ) and Clinical Pharmacology ( 12.3 )] . Antiepileptic Drugs Clinical Impact 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 [see Clinical Pharmacology ( 12.3 )] . 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). Intervention Consider measuring blood ammonia in patients in whom the onset of hypothermia or encephalopathy has been reported [see Clinical Pharmacology ( 12.3 )] . Carbonic Anhydrase Inhibitors Clinical Impact 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. Intervention Avoid the use of phentermine and topiramate extended-release capsules with other drugs that inhibit carbonic anhydrase. If concomitant use of phentermine and topiramate extended-release capsules with another carbonic anhydrase inhibitor is unavoidable, monitor patient for the appearance or worsening of metabolic acidosis [see Warnings and Precautions ( 5.7 , 5.10 )] . Pioglitazone Clinical Impact 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. Intervention Consider increased glycemic monitoring when using pioglitazone and phentermine and topiramate extended-release capsules concomitantly [see Clinical Pharmacology ( 12.3 )] . Amitriptyline Clinical Impact Some patients may experience a large increase in amitriptyline concentration in the presence of topiramate. Intervention Any adjustments in amitriptyline dose when used with phentermine and topiramate extended-release capsules should be made according to the patient's clinical response and not on the basis of amitriptyline levels [see Clinical Pharmacology ( 12.3 )] .
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
9 DRUG ABUSE AND DEPENDENCE
DRUG ABUSE AND DEPENDENCE SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
In the event of a significant overdose with phentermine and topiramate extended-release capsules, if the ingestion is recent, the stomach should be emptied immediately by gastric lavage or by induction of emesis. Appropriate supportive treatment should be provided according to the patient’s clinical signs and symptoms. In the event of an overdose of phentermine and topiramate extended-release capsules, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Acute overdose of phentermine may be associated with restlessness, tremor, hyperreflexia, rapid respiration, confusion, aggressiveness, hallucinations, and panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmia, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma. Manifestations of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. A severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. Management of acute phentermine intoxication is largely symptomatic and includes lavage and sedation with a barbiturate. Acidification of the urine increases phentermine excretion. Intravenous phentolamine has been suggested for possible acute, severe hypertension, if this complicates phentermine overdosage. Topiramate overdose has resulted in severe metabolic acidosis. Other signs and symptoms include convulsions, drowsiness, speech disturbance, blurred vision, diplopia, impaired mentation, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness, and depression. The clinical consequences were not severe in most cases, but deaths have been reported after overdoses involving topiramate. A patient who ingested a dose between 96 and 110 gm topiramate was admitted to hospital with coma lasting 20 to 24 hours followed by full recovery after 3 to 4 days. Hemodialysis is an effective means of removing topiramate from the body.
11 DESCRIPTION
DESCRIPTION SECTION
Phentermine and topiramate extended-release capsules are comprised of immediate-release phentermine hydrochloride (expressed as the weight of the free base) and extended-release topiramate. Phentermine and topiramate extended-release capsules contain phentermine hydrochloride USP, a sympathomimetic amine anorectic, and topiramate USP, a sulfamate-substituted monosaccharide. Phentermine Hydrochloride, USP The chemical name of phentermine hydrochloride, USP is α,α-dimethylphenethylamine hydrochloride. The molecular formula is C 10 H 15 N • HCl and its molecular weight is 185.7 (hydrochloride salt) or 149.2 (free base). Phentermine hydrochloride, USP is a white, odorless, hygroscopic, crystalline powder that is soluble in water, methanol, and ethanol. Its structural formula is: Topiramate, USP Topiramate, USP is 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose sulfamate. The molecular formula is C 12 H 21 NO 8 S and its molecular weight is 339.4. Topiramate, USP is a white to off-white crystalline powder with a bitter taste. It is freely soluble in methanol and acetone, sparingly soluble in pH 9 to pH 12 aqueous solutions and slightly soluble in pH 1 to pH 8 aqueous solutions. Its structural formula is: Phentermine and topiramate extended-release capsules are for oral administration and available in four dosage strengths: 3.75 mg/23 mg (phentermine 3.75 mg and topiramate 23 mg extended-release) (equivalent to 4.67 mg of phentermine hydrochloride, USP). 7.5 mg/46 mg (phentermine 7.5 mg and topiramate 46 mg extended-release) (equivalent to 9.33 mg of phentermine hydrochloride, USP). 11.25 mg/69 mg (phentermine 11.25 mg and topiramate 69 mg extended-release) (equivalent to 14.0 mg of phentermine hydrochloride, USP). 15 mg/92 mg (phentermine 15 mg and topiramate 92 mg extended-release) (equivalent to 18.66 mg of phentermine hydrochloride, USP). Each capsule contains the following inactive ingredients: colloidal silicon dioxide, copovidone, ethylcellulose, gelatin, hypromellose, microcrystalline cellulose, polysorbate 80, povidone K-30, sugar spheres (which contain sucrose and corn starch), talc, and titanium dioxide. The 3.75 mg/23 mg strength also contains iron oxide red and iron oxide yellow. The 7.5 mg/46 mg strength also contains FD&C Blue #2 and iron oxide yellow. The 11.25 mg/69 mg strength also contains iron oxide yellow. The 15 mg/92 mg strength also contains iron oxide red. The imprinting ink contains ammonium hydroxide, iron oxide black, propylene glycol, and shellac glaze.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
Clinical Studies in Adults The effect of phentermine and topiramate extended-release capsules on weight loss in conjunction with reduced caloric intake and increased physical activity was studied in two randomized, double-blind, placebo-controlled studies in patients with obesity (Study 1) and patients with obesity or overweight with two or more significant co-morbidities (Study 2). Both studies had a 4-week titration period, followed by 52 weeks of treatment. There were two co-primary efficacy outcomes measured after 1 year of treatment (Week 56): 1) the percent weight loss from baseline; and 2) treatment response defined as achieving at least 5% weight loss from baseline. In Study 1, patients with obesity (BMI greater than or equal to 35 kg/m 2 ) were randomized to receive 1 year of treatment with placebo (N=514), phentermine and topiramate extended-release capsules 3.75 mg/23 mg (N=241), or phentermine and topiramate extended-release capsules 15 mg/92 mg (N=512) in a 2:1:2 ratio. Patients ranged in age from 18-71 years old (mean age 43) and 83% were female. Approximately 80% were White, 18% were Black or African American, and 15% were Hispanic or Latino ethnicity. At the beginning of the study the average weight and BMI of patients was 116 kg and 42 kg/m 2 , respectively. Patients with type 2 diabetes mellitus 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), phentermine and topiramate extended-release capsules 7.5 mg/46 mg (N=498), or phentermine and topiramate extended-release capsules 15 mg/92 mg (N=995) in a 2:1:2 ratio. Eligible patients had to have a BMI greater than or equal to 27 kg/m 2 and less than or equal to 45 kg/m 2 (there was no lower limit on BMI for patients with type 2 diabetes mellitus) and two or more of the following obesity-related co-morbid conditions: Elevated blood pressure (greater than or equal to 140/90 mmHg, or greater than or equal to 130/85 mmHg for diabetics) or requirement for greater than or equal to 2 antihypertensive medications; Triglycerides greater than 200 to 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 females. Patients ranged in age from 19 to 71 years of age (mean age 51) and 70% were female. Approximately 86% were White, 12% were Black or African American, and 13% were Hispanic or Latino ethnicity. The average weight and BMI of patients at the start of the study was 103 kg and 36.6 kg/m 2 , respectively. Approximately half (53%) of patients had hypertension at the start of the study. There were 388 (16%) patients with type 2 diabetes mellitus 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. The percentage of randomized patients who withdrew from each study prior to week 56 was 40% in Study 1, and 31% in Study 2. Table 10 provides the results for weight loss at 1 year in Studies 1 and 2. After 1 year of treatment with phentermine and topiramate extended-release capsules, all dose levels resulted in statistically significant weight loss compared to placebo (see Table 10, Figure 1 and Figure 2). A statistically significant greater proportion of the patients randomized to phentermine and topiramate extended-release capsules than placebo achieved 5% and 10% weight loss. Table 10. Weight Loss at One Year in Adult Patients in Studies 1 and 2 Analysis Method Study 1 (Obesity) Study 2 (Obesity or Overweight with Co-morbidities) Placebo Phentermine and Topiramate Extended-Release Capsules 3.75 mg/23 mg Phentermine and Topiramate Extended-Release Capsules 15 mg/92 mg Placebo Phentermine and Topiramate Extended-Release Capsules 7.5 mg/46 mg Phentermine and Topiramate Extended-Release Capsules 15 mg/92 mg ITT-LOCF (Primary)* n = 498 n = 234 n = 498 n = 979 n = 488 n = 981 Weight (kg) Baseline mean (SD) 115.7 (21.4) 118.6 (21.9) 115.2 (20.8) 103.3 (18.1) 102.8 (18.2) 103.1 (17.6) % LS Mean Change from baseline (SE)** -1.6 (0.4) -5.1 (0.5) † -10.9 (0.4) †‡ -1.2 (0.3) -7.8 (0.4) † -9.8 (0.3) †‡ Difference from placebo (95% CI) 3.5 (2.4 to 4.7) 9.4 (8.4 to 10.3) 6.6 (5.8 to 7.4) 8.6 (8.0 to 9.3) Percentage of patients losing greater than or equal to 5% body weight 17% 45% † 67% †‡ 21% 62% † 70% †‡ Risk Difference vs. placebo (95% CI) 27.6 (20.4 to 34.8) 49.4 (44.1 to 54.7) 41.3 (36.3 to 46.3) 49.2 (45.4 to 53.0) Percentage of patients losing greater than or equal to 10% body weight 7% 19% † 47% †‡ 7% 37% † 48% †‡ Risk Difference vs. placebo (95% CI) 11.4 (5.9 to 16.9) 39.8 (34.8 to 44.7) 29.9 (25.3 to 34.5) 40.3 (36.7 to 43.8) SD=standard deviation; LS=least-squares; SE=standard error; CI=confidence interval * Uses all available data from subjects in ITT population, including data collected from subjects who discontinued drug but remained on study. Last Observation Carried Forward (LOCF) method used to impute missing data. † p < 0.0001 vs. placebo based on least-squares (LS) mean from an analysis of covariance. ‡ p < 0.01 vs. 3.75 mg/23 mg (Study 1) or 7.5 mg/46 mg (Study 2) dose. Type 1 error was controlled across all pairwise treatment comparisons. ** Adjusted for baseline bodyweight (Study 1) and baseline bodyweight and diabetic status (Study 2). Figure 1. Study 1 Percent Weight Change from Baseline to Week 56 in Adults with Obesity Figure 2. Study 2 Percent Weight Change from Baseline to Week 56 in Adults with Obesity or Overweight with Co-morbidities The changes in cardiovascular, metabolic, and anthropometric risk factors associated with obesity from Study 1 and 2 are presented in Table 11 and Table 12. Table 11. Least-Squares (LS) Mean † Change from Baseline and Treatment Difference from Placebo in Cardiometabolic Parameters in Adults Following One Year of Treatment in Study 1 (Obesity) Study 1 (Obesity) Placebo (N=498) Phentermine and Topiramate Extended-Release Capsules 3.75 mg/23 mg (N=234) Phentermine and Topiramate Extended-Release Capsules 15 mg/92 mg (N=498) Phentermine and Topiramate Extended-Release Capsules – Placebo: LS Mean Phentermine and Topiramate Extended-Release Capsules 3.75 mg/23 mg Phentermine and Topiramate Extended-Release Capsules 15 mg/92 mg Heart Rate, bpm Baseline mean (SD) 73.2 (8.8) 72.3 (9.2) 73.1 (9.6) +1.1 +1.8 LS Mean Change (SE) -0.8 (0.5) +0.3 (0.6) +1.0 (0.5) Systolic Blood Pressure, mmHg Baseline mean (SD) 121.9 (11.5) 122.5 (11.1) 121.9 (11.6) -2.8 -3.8 LS Mean Change (SE) +0.9 (0.6) -1.8 (0.8) -2.9 (0.6) Diastolic Blood Pressure, mmHg Baseline mean (SD) 77.2 (7.9) 77.8 (7.5) 77.4 (7.7) -0.5 -1.9 LS Mean Change (SE) +0.4 (0.4) -0.1 (0.6) -1.5 (0.4) Total Cholesterol, % Baseline mean (SD) 194.3 (36.7) 196.3 (36.5) 192.7 (33.8) -1.9 -2.5 LS Mean Change (SE) -3.5 (0.6) -5.4 (0.9) -6.0 (0.6) LDL-Cholesterol, % Baseline mean (SD) 120.9 (32.2) 122.8 (33.4) 120.0 (30.1) -2.2 -2.8 LS Mean Change (SE) -5.5 (1.0) -7.7 (1.3) -8.4 (0.9) HDL-Cholesterol, % Baseline mean (SD) 49.5 (13.3) 50.0 (11.1) 49.7 (11.7) +0.5 +3.5 LS Mean Change (SE) +0.0 (0.8) +0.5 (1.1) +3.5 (0.8) Triglycerides, % Baseline mean (SD) 119.0 (39.3) 117.5 (40.3) 114.6 (37.1) -3.9 -14.3 LS Mean Change (SE) +9.1 (2.3) +5.2 (3.1) -5.2 (2.2) Fasting Glucose, mg/dL Baseline mean (SD) 93.1 (8.7) 93.9 (9.2) 93.0 (9.5) -1.2 -2.5 LS Mean Change (SE) +1.9 (0.5) +0.8 (0.7) -0.6 (0.5) Waist Circumference, cm Baseline mean (SD) 120.5 (14.0) 121.5 (15.2) 120.0 (14.7) -2.5* -7.8* LS ...
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
Phentermine and topiramate extended-release capsules are available as follows (see Table 15): Table 15. Phentermine and Topiramate Extended-Release Capsules Presentations Strength (phentermine mg/topiramate mg) Description How Supplied NDC # 3.75 mg/23 mg extended-release capsules White opaque cap printed with WPI, orange opaque body printed with 2196 Unit of Use Bottle (30 capsules) 0480-3297-56 7.5 mg/46 mg extended-release capsules White opaque cap printed with WPI, green opaque body printed with 2195 Unit of Use Bottle (30 capsules) 0480-3296-56 11.25 mg/69 mg extended-release capsules Light yellow opaque cap printed with WPI, white opaque body printed with 2299 Unit of Use Bottle (30 capsules) 0480-2299-56 15 mg/92 mg extended-release capsules White opaque cap printed with WPI, dark scarlet opaque body printed with 2194 Unit of Use Bottle (30 capsules) 0480-3295-56 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep container tightly closed and protect from moisture. Keep out of reach of children.
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Embryo-Fetal Toxicity Inform patients who can become pregnant that phentermine and topiramate extended-release capsules can cause fetal harm and patients should avoid getting pregnant while taking phentermine and topiramate extended-release capsules [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7 ), and Use in Specific Populations ( 8.3 )] . Advise patients who can become pregnant: that pregnancy testing is recommended before initiating phentermine and topiramate extended-release capsules and monthly during therapy; to use effective contraception during phentermine and topiramate extended-release capsule therapy; who experience spotting while taking a combined oral contraceptive to notify their health care provider; with a known or suspected pregnancy to stop phentermine and topiramate extended-release capsules immediately and notify their health care provider. Access to Phentermine and Topiramate Extended-Release Capsules Advise patients that phentermine and topiramate extended-release capsules is only available through certified pharmacies that are enrolled in the phentermine and topiramate extended-release capsules certified pharmacy network. Advise patients on how to access phentermine and topiramate extended-release capsules through certified pharmacies. Additional information may be obtained via the website www.PhenTopREMS.com or by telephone at 1-800-269-6816 or by FAX at 1-800-558-6165. Suicidal Behavior and Ideation and Mood and Sleep Disorders Inform patients that phentermine and topiramate extended-release capsules can increase the risk of mood changes, sleep disorders, depression, and suicidal ideation. Advise patients to tell their health care provider(s) immediately if mood changes, depression, or suicidal ideation occur [see Warnings and Precautions ( 5.2 , 5.4 )] . Ophthalmologic Adverse Reactions Inform patients that phentermine and topiramate extended-release capsules can increase the risk of acute myopia, secondary angle closure glaucoma, and visual field defects. Advise patients to immediately report symptoms of severe and persistent eye pain or significant changes in their vision to their health care provider(s) [see Warnings and Precautions ( 5.3 )] . Cognitive Impairment Inform patients that phentermine and topiramate extended-release capsules can cause confusion, concentration, and word-finding difficulties. Inform patients that the concomitant use of alcohol or central nervous system (CNS) depressant drugs with phentermine and topiramate extended-release capsules, may increase the risk of dizziness, cognitive adverse reactions, drowsiness, light-headedness, impaired coordination and somnolence. Advise patients to tell their health care 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 phentermine and topiramate extended-release capsules to gauge whether it adversely affects their mental performance, motor performance, and/or vision. Advise patients to avoid excessive alcohol intake while taking phentermine and topiramate extended-release capsules [see Warnings and Precautions ( 5.5 )] . Slowing of Linear Growth Discuss with the patient and caregiver that long-term phentermine and topiramate extended-release capsules treatment may attenuate growth as reflected by slower height increase in pediatric patients [see Warnings and Precautions ( 5.6 )] . Metabolic Acidosis Inform patients that phentermine and topiramate extended-release capsules can increase the risk of metabolic acidosis. Advise patients to tell their health care provider(s) about any factors that can increase the risk of acidosis (e.g. prolonged diarrhea, surgery, and high protein/low carbohydrate diet, and/or concomitant medications such as carbonic anhydrase inhibitors) [see Warnings and Precautions ( 5.7 )] . Risk of Seizures with Abrupt Withdrawal of Phentermine and Topiramate Extended-Release Capsules Inform patients that abrupt withdrawal of topiramate has been associated with seizures in individuals without a history of seizures or epilepsy. Advise patients not to abruptly stop phentermine and topiramate extended-release capsules without first talking to their health care provider(s) [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.9 )] . Kidney Stones Inform patients that use of phentermine and topiramate extended-release capsules 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 health care provider(s) [see Warnings and Precautions ( 5.10 ) and Adverse Reactions ( 6.1 )] . Oligohidrosis and Hyperthermia Inform patients that oligohidrosis (decreased sweating) has been reported in association with the use of topiramate, particularly in pediatric patients. Advise patients to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather [see Warnings and Precautions ( 5.11 )] . Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions Instruct patients that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related. Advise patients to report such reactions to a healthcare provider immediately [see Warnings and Precautions ( 5.13 )] . Serious Skin Reactions Inform patients about the signs of serious skin reactions. Instruct patients to immediately inform their healthcare provider at the first appearance of skin rash [see Warnings and Precautions ( 5.14 )] . Anaphylaxis and Angioedema Inform patients about the signs and symptoms of hypersensitivity reactions such as anaphylaxis and angioedema, which can occur with phentermine and topiramate extended-release capsules. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions ( 5.15 )] . Lactation Advise patients that breastfeeding is not recommended during phentermine and topiramate extended-release capsule treatment [see Use in Specific Populations ( 8.2 )] . How to Take Phentermine and Topiramate Extended-Release Capsules Instruct patients on the dosage titration schedule of phentermine and topiramate extended-release capsules. Advise patients to take phentermine and topiramate extended-release capsules in the morning with or without food [see Dosage and Administration ( 2.2 )] . Brands listed are the trademarks of their respective owners. Dispense with Medication Guide available at: www.tevausa.com/medguides Manufactured In Bulgaria By: Balkanpharma Dupnitsa AD Dupnitsa 2600, Bulgaria Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. D 3/2026
SPL MEDGUIDE SECTION
SPL MEDGUIDE SECTION
Dispense with Medication Guide available at: www.tevausa.com/medguides MEDICATION GUIDE Phentermine (fen' ter meen) and Topiramate (toe pir' a mate) Extended-Release Capsules for oral use, CIV What is the most important information I should know about phentermine and topiramate extended-release capsules ? Phentermine and topiramate extended-release capsules can cause serious side effects, including: Birth defects. If you take phentermine and topiramate extended-release capsules during pregnancy, your baby has a higher risk for birth defects including cleft lip and cleft palate. Your baby may also be smaller than expected at birth. The long-term effects of this are not known. These defects can begin early in pregnancy, even before you know you are pregnant. Patients who are pregnant must not take phentermine and topiramate extended-release capsules . Patients who can become pregnant should: Have a pregnancy test before taking phentermine and topiramate extended-release capsules and every month while taking phentermine and topiramate extended-release capsules. Use effective birth control (contraception) consistently while taking phentermine and topiramate extended-release capsules. Talk to your health care provider about how to prevent pregnancy. If you become pregnant while taking phentermine and topiramate extended-release capsules , stop taking phentermine and topiramate extended-release capsules immediately and tell your health care provider right away. Health care providers and patients who become pregnant should report all cases of pregnancy to: FDA MedWatch at 1-800-FDA-1088 Because of the risk for birth defects (cleft lip and cleft palate), phentermine and topiramate extended-release capsules are available through a restricted program called the Phentermine and Topiramate Extended-Release Capsules Risk Evaluation and Mitigation Strategy (REMS) . Phentermine and topiramate extended-release capsules are only available through certified pharmacies that participate in the Phentermine and Topiramate Extended-Release Capsules REMS. Your health care provider can give you information about how to find a certified pharmacy. For more information, go to www.PhenTopREMS.com or call 1-800-269-6816. Suicidal thoughts or actions. Topiramate, an ingredient in phentermine and topiramate extended-release capsules, may cause you to have suicidal thoughts or actions. Call your health care provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying attempts to commit suicide new or worse depression new or worse anxiety feeling agitated or restless panic attacks trouble sleeping (insomnia) new or worse irritability acting aggressive, being angry, or violent acting on dangerous impulses an extreme increase in activity and talking (mania) other unusual changes in behavior or mood Do not stop phentermine and topiramate extended-release capsules without first talking to a health care provider. Stopping phentermine and topiramate extended-release capsules suddenly can cause serious problems. Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your health care provider may check for other causes. How can I watch for early symptoms of suicidal thoughts and actions? Pay attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings. Keep all follow-up visits with your health care provider as scheduled. Call your health care provider between visits as needed, especially if you are worried about symptoms. Serious eye problems which include: any sudden decrease in vision, with or without eye pain and redness, a blockage of fluid in the eye causing increased pressure in the eye (secondary angle closure glaucoma). These problems can lead to permanent vision loss if not treated. Tell your health care provider right away if you have any new eye symptoms. Phentermine and topiramate extended-release capsules can have other serious side effects. See “What are the possible side effects of phentermine and topiramate extended-release capsules ?”. What are phentermine and topiramate extended-release capsules ? Phentermine and topiramate extended-release capsules are a prescription medicine that contains phentermine and topiramate extended-release. Phentermine and topiramate extended-release capsules may help adults and children 12 years and older with obesity, or some adults with overweight who also have weight-related medical problems, to help them lose excess body weight and keep the weight off. Phentermine and topiramate extended-release capsules should be used with a reduced calorie diet and increased physical activity. It is not known if phentermine and topiramate extended-release capsules change your risk of heart problems or stroke or of death due to heart problems or stroke. It is not known if phentermine and topiramate extended-release capsules are safe and effective when taken with other prescription and over-the-counter medicines, or herbal weight loss products. It is not known if phentermine and topiramate extended-release capsules are safe and effective in children under 12 years old. Phentermine and topiramate extended-release capsules are a federally controlled substance (CIV) because it contains phentermine and can be abused or lead to drug dependence. Keep phentermine and topiramate extended-release capsules in a safe place, to protect it from theft. Never give your phentermine and topiramate extended-release capsules to anyone else, because it may cause death or harm them. Selling or giving away phentermine and topiramate extended-release capsules is against the law. Who should not take phentermine and topiramate extended-release capsules ? Do not take phentermine and topiramate extended-release capsules if you: are pregnant, planning to become pregnant, or become pregnant during phentermine and topiramate extended-release capsule treatment. have glaucoma. have thyroid problems (hyperthyroidism). are taking certain medicines called monoamine oxidase inhibitors (MAOIs) or have taken MAOIs in the past 14 days. are allergic to topiramate, sympathomimetic amines such as phentermine, or any of the ingredients in phentermine and topiramate extended-release capsules. See the end of this Medication Guide for a complete list of ingredients in phentermine and topiramate extended-release capsules. Before taking phentermine and topiramate extended-release capsules , tell your health care provider about all of your medical conditions, including if you: have or have had depression, mood problems, or suicidal thoughts or behavior. have eye problems, especially glaucoma. See “Who should not take phentermine and topiramate extended-release capsules ?” have a history of too much acid in the blood (metabolic acidosis) or a condition that puts you at higher risk for metabolic acidosis such as chronic diarrhea, surgery, a diet high in fat and low in carbohydrates (ketogenic diet), weak, brittle, or soft bones (osteoporosis, osteomalacia (rickets), osteopenia), or decreased bone density. have kidney problems, kidney stones, or are getting kidney dialysis. have liver problems. have seizures or convulsions (epilepsy). are breastfeeding or plan to breastfeed. Phentermine and topiramate can pass into your breast milk and may harm your baby. You and your health care provider should decide if you will take phentermine and topiramate extended-release capsules or breastfeed. You should not do both. Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Phentermine and topiramate extended-release capsules taken with other medicines may affect how each medicine works and may cause side effects. Especially tell your health care provider if you take: Birth control pills. Tell your health care provider if your menstrual bleeding chan...
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0480-3297-56 Phentermine and Topiramate Extended-release Capsules CIV 3.75 mg/23 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Capsules
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0480-3296-56 Phentermine and Topiramate Extended-release Capsules CIV 7.5 mg/46 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Capsules
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0480-2299-56 Phentermine and Topiramate Extended-release Capsules CIV 11.25 mg/69 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Capsules
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 0480-3295-56 Phentermine and Topiramate Extended-release Capsules CIV 15 mg/92 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Capsules
