Home › Drugs › Phentermine And Topiramate Extended-Release

Phentermine And Topiramate Extended-Release

FDA Drug Information • Also known as: Phentermine And Topiramate Extended-Release

Brand Names
Phentermine And Topiramate Extended-Release
Route
ORAL
Dosage Form
CAPSULE
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Phentermine and topiramate extended-release capsules are comprised of immediate-release phentermine hydrochloride, USP (expressed as the weight of the free base) and extended-release topiramate, USP. 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 16 ClN and its molecular weight is 185.69 g mol -1 (hydrochloride salt) or 149.2 (free base). Phentermine hydrochloride, USP is a white, odourless, hygroscopic, crystalline powder that is soluble in water and lower alcohols. It is also slightly soluble in chloroform and insoluble in ether. 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 339.36.Topiramate, USP is a white to off-white powder. It is freely soluble in dichloromethane. Its structural formula is: Phentermine and Topiramate Extended-Release Capsules 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 USP, 23 mg) (equivalent to 4.665 mg of Phentermine Hydrochloride, USP).
  • 7.5 mg/46 mg (phentermine 7.5 mg and topiramate USP, 46 mg) (equivalent to 9.33 mg of Phentermine Hydrochloride, USP).
  • 11.25 mg/69 mg (phentermine 11.25 mg and topiramate USP, 69 mg) (equivalent to 14 mg of Phentermine Hydrochloride, USP).
  • 15 mg/92 mg (phentermine 15 mg and topiramate USP, 92 mg) (equivalent to 18.66 mg of Phentermine Hydrochloride, USP). Each capsule contains the following inactive ingredients: ethocel, gelatin, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, talc and titanium dioxide....

    • What Is Phentermine And Topiramate Extended-Release Used For?

    1 INDICATIONS AND USAGE 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: Adult patients 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. Pediatric use information is approved for Vivus LLC's Qsymia ® (phentermine and topiramate) extended-release capsules. However, due to Vivus LLC's marketing exclusivity rights, this drug product is not labeled with that information. Phentermine and topiramate extended-release capsules are a combination of phentermine, a sympathomimetic amine anorectic, and topiramate indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adult patients with obesity ( 1 ) 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 ( 1 ). The safety and effectiveness of phentermine and topiramate extended-release capsules in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, have not been established ( 1 ).

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION

  • Take orally once daily in morning. Avoid administration in evening to prevent insomnia ( 2.2 ).
  • Recommended starting dosage is 3.75 mg/23 mg (phentermine mg/topiramate mg) daily for 14 days; then increase to 7.5 mg/46 mg daily ( 2.2 ).
  • Escalate dosage based on weight loss in adults. See the Full Prescribing Information for details regarding discontinuation or dosage escalation. ( 2.2 ).
  • Gradually discontinue 15 mg/92 mg dosage to prevent possible seizure ( 2.3 ).
  • Do not exceed 7.5 mg/46 mg dosage for patients with moderate or severe renal impairment or patients with moderate hepatic impairment ( 2.4 , 2.5 ). 2.1 Recommended Testing Prior to and During Treatment with Phentermine and Topiramate Extended-Release Capsules Prior to phentermine and topiramate extended-release capsules initiation and during treatment with phentermine and topiramate extended-release capsules, the following is recommended: Obtain a negative pregnancy test before initiating phentermine and topiramate extended-release capsules in patients who can become pregnant and monthly during phentermine and topiramate extended-release capsules therapy. Phentermine and topiramate extended-release capsules are contraindicated during pregnancy [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.3 )] . Obtain a blood chemistry profile that includes bicarbonate, creatinine, and potassium in all patients, and glucose in patients with type 2 diabetes mellitus on antidiabetic medication prior to initiating phentermine and topiramate extended-release capsules treatment and periodically during treatment [see Warnings and Precautions ( 5.7 , 5.8 , 5.12 )]. 2.2 Recommended Dosage and Administration The recommended dosage, titration, and administration of phentermine and topiramate extended-release capsules are as follows: Take phentermine and topiramate extended-release capsules orally once daily in the morning with or without food. Avoid administration of phentermine and topiramate extended-release capsules in the evening due to the possibility of insomnia. The recommended starting dosage of phentermine and topiramate extended-release capsules is one capsule (containing 3.75 mg of phentermine and 23 mg of topiramate) (3.75 mg/23 mg) taken orally once daily for 14 days; after 14 days increase to the recommended dosage of phentermine and topiramate extended-release capsules 7.5 mg/46 mg orally once daily. After 12 weeks of treatment with phentermine and topiramate extended-release capsules 7.5 mg/46 mg, evaluate weight loss for adults. If an adult patient has not lost at least 3% of baseline body weight, increase the dosage to phentermine and topiramate extended-release capsules 11.25 mg/69 mg orally once daily for 14 days; followed by an increase in the dosage to phentermine and topiramate extended-release capsules 15 mg/92 mg orally once daily. After 12 weeks of treatment with phentermine and topiramate...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS 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 )] Oligohydrosis and Hyperthermia [see Warnings and Precautions ( 5.11 )] Hypokalemia [see Warnings and Precautions ( 5.12 )] Serious Skin Reactions [see Warnings and Precautions ( 5.13 )] Most common adverse reactions in:

  • Adults (incidence ≥ 5% and at least 1.5 times placebo) are: paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The data described herein reflect exposure to phentermine and topiramate extended-release in two 1-year, randomized, double-blind, placebo-controlled, multicenter clinical trials and two supportive trials in 2,318 adult patients with overweight or obesity [936 (40%) patients with hypertension, 309 (13%) patients with type 2 diabetes mellitus, 808 (35%) patients with BMI greater than 40 kg/m 2 ] exposed for a mean duration of 298 days [see Clinical Studies ( 14 )]. Adults Adverse reactions occurring at greater than or equal to 5% and at least 1.5 times placebo in adults include paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. Adverse reactions reported in greater than or equal to 2% of phentermine and topiramate extended-release-treated adults and more frequently than in the placebo group are shown in Table 1. Table 1. Adverse Reactions Reported in ≥2% of Phentermine and Topiramate Extended-Release-Treated Adults with Overweight or Obesity and More Frequently than Placebo in Overall Study Population of 1 Year Duration Adverse Reaction Placebo (N = 1561) % Phentermine and topiramate extended-release 3.75 mg/23 mg (N = 240) % Phentermine and topiramate extended-release 7.5 mg/46 mg (N = 498) % Phentermine and topiramate extended-release 15 mg/92 mg (N = 1,580) % Paraesthesia 2 4 14 20 Dry Mouth 3 7 14 19 Constipation 6 8 15 16 Upper Respiratory Tract Infection 13 16 12 14 Headache 9 10 7 11 Dysgeusia 1 1 7 9 Insomnia 5 5 6 9 Nasopharyngitis 8 13 11 9 Dizziness 3 3 7 9 Sinusitis 6 8 7 8 Nausea 4 6 4 7 Back Pain 5 5 6 7 Fatigue 4 5 4 6 Diarrhea 5 5 6 6 Vision Blurred 4 6 4 5 Bronchitis 4 7 4 5 Urinary Tract Infection 4 3 5 5 Cough 4 3 4 5 Influenza 4 8 5 4 Depression 2 3 3 4 Anxiety 2 3 2 4 Hypoesthesia 1 1 4 4 Irritability 1 2 3 4 Alopecia 1 2 3 4 Disturbance in Attention 1 0 2 4 Pain in Extremity 3 2 3 3 Muscle Spasms 2 3 3 3 Dyspepsia 2 2 2 3 Gastroesophageal Reflux Disease 1 1 3 3 Rash 2 2 2 3 Hypokalemia 0 0 1 3 Dry Eye 1 1 1 3 Gastroenteritis 2 1 2 3 Pharyngolaryngeal Pain 2 3 1 2 Paraesthesia Oral 0 0 1 2 Eye Pain 1 2 2 2 Nasal Congestion 1 2 1 2 Thirst 1 2 2 2 Sinus Congestion 2 3 3 2 Procedural Pain 2 2 2 2 Palpitations 1 1 2 2 Musculoskeletal Pain 1 1 3 2 Decreased Appetite 1 2 2 2 Neck Pain 1 1 2 1 Dysmenorrhea 0 2 0 1 Chest Discomfort 0 2 0 1 Increase...

    • Drug Interactions

    7 DRUG INTERACTIONS 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 are contraindicated during MAOI treatment and within 14 days of stopping an MAOI. Oral Contraceptives Clinical Impact Co-administration of multiple-dose phentermine and topiramate extended-release 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 capsules 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 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 capsules treatment [see Warnings and...

    Contraindications

    4 CONTRAINDICATIONS 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 )]
  • Wjith 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 amine [see Adverse Reactions ( 6.2 )].
  • Pregnancy ( 4 )
  • Glaucoma ( 4 )
  • Hyperthyroidism ( 4 )
  • Taking or within 14 days of stopping monoamine oxidase inhibitors ( 4 )
  • Known hypersensitivity to any component of phentermine and topiramate extended-release capsules or idiosyncrasy to sympathomimetic amines ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Phentermine and topiramate extended-release capsules are contraindicated in pregnant patients. The use of phentermine and topiramate extended-release capsules can cause fetal harm and weight loss offers no clear clinical benefit to a pregnant patient (see Clinical Considerations) . Available data from pregnancy registries and epidemiologic studies indicate an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being SGA in infants exposed in utero to topiramate (see Data) . When phentermine and topiramate were co-administered to rats at doses of 3.75 and 25 mg/kg, respectively [approximately 2 times the maximum recommended human dose (MRHD) based on area under the curve (AUC)], or at the same dose to rabbits (approximately 0.1 times and 1 time, respectively, the clinical exposures at the MRHD based on AUC), there were no drug-related malformations. However, structural malformations, including craniofacial defects and reduced fetal weights occurred in offspring of multiple species of pregnant animals administered topiramate at clinically relevant doses (see Data) . Advise pregnant women of the potential risk to a fetus. Clinical Considerations Disease Associated Maternal and/or Embryo/Fetal Risk Weight loss during pregnancy may result in fetal harm. Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. Maternal obesity increases the risk for congenital malformations, including neural tube defects, cardiac malformations, oral clefts, and limb reduction defects. Fetal/Neonatal Adverse Reactions Phentermine and topiramate extended-release capsules can cause metabolic acidosis [see Warnings and Precautions ( 5.7 )] . The effect of topiramate-induced metabolic acidosis has not been...

    Overdosage

    10 OVERDOSAGE 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...

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Phentermine and topiramate extended-release capsules are available as follows:

  • Phentermine and topiramate extended-release capsules, 3.75 mg/23 mg are two-piece hard gelatin capsule with white opaque cap and white opaque body, filled with white to pale yellow pellets, imprinted in black ink with DRL on cap and 624 on body. Free from physical defects. They are supplied in: Bottles of 14 43598-624-13 Bottles of 30 43598-624-30 Bottles of 100 43598-624-01
  • Phentermine and topiramate extended-release capsules 7.5 mg/46 mg are two-piece hard gelatin capsule with red opaque cap and white opaque body, filled with white to pale yellow pellets, imprinted in black ink with DRL on cap and 625 on body. Free from physical defects. They are supplied in: Bottles of 30 43598-625-30 Bottles of 100 43598-625-01
  • Phentermine and topiramate extended-release capsules, 11.25 mg/69 mg are two-piece hard gelatin capsule with green opaque cap and white opaque body, filled with white to pale yellow pellets, imprinted in black ink with DRL on cap and 626 on body. Free from physical defects. They are supplied in: Bottles of 30 43598-626-30 Bottles of 100 43598-626-01
  • Phentermine and topiramate extended-release capsules, 15 mg/92 mg are elongated two-piece hard gelatin capsule with orange opaque cap and white opaque body, filled with white to pale yellow pellets, imprinted in black ink with DRL on cap and 627 on body. Free from physical defects. They are supplied in: Bottles of 30 43598-627-30 Bottles of 100 43598-627-01 Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Keep container tightly closed and protect from moisture.

    • About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.