Phentermine and Topiramate

Name: Phentermine and Topiramate

Description

Qsymia capsule is a combination oral product comprised of immediate-release phentermine hydrochloride (expressed as the weight of the free base) and extended-release topiramate. Qsymia contains phentermine hydrochloride, a sympathomimetic amine anorectic, and topiramate, a sulfamate-substituted monosaccharide related to fructose antiepileptic drug.

Phentermine Hydrochloride

The chemical name of phentermine hydrochloride is α,α-dimethylphenethylamine hydrochloride. The molecular formula is C10H15N •HCl and its molecular weight is 185.7 (hydrochloride salt) or 149.2 (free base). Phentermine hydrochloride is a white, odorless, hygroscopic, crystalline powder that is soluble in water, methanol, and ethanol. Its structural formula is:

Topiramate

Topiramate is 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose sulfamate. The molecular formula is C12H21NO8S and its molecular weight is 339.4. Topiramate 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:

Qsymia

Qsymia is available in four dosage strengths:

  • Qsymia 3.75 mg/23 mg (phentermine 3.75 mg and topiramate 23 mg extended-release) capsules;
  • Qsymia 7.5 mg/46 mg (phentermine 7.5 mg and topiramate 46 mg extended-release) capsules;
  • Qsymia 11.25 mg/69 mg (phentermine 11.25 mg and topiramate 69 mg extended-release) capsules;
  • Qsymia 15 mg/92 mg (phentermine 15 mg and topiramate 92 mg extended-release) capsules.

Each capsule contains the following inactive ingredients: methylcellulose, sucrose, starch, microcrystalline cellulose, ethylcellulose, povidone, gelatin, talc, titanium dioxide, FD&C Blue #1, FD&C Red #3, FD&C Yellow #5 and #6, and pharmaceutical black and white inks.

What should i avoid while taking phentermine and topiramate (qsymia)?

Do not take any other prescription or over-the-counter weight-loss products without your doctor's advice.

Drinking alcohol can increase certain side effects of phentermine and topiramate.

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Where can i get more information?

Your pharmacist can provide more information about phentermine and topiramate.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.01. Revision date: 8/15/2012.

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What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of phentermine and topiramate can be fatal.

Overdose symptoms may include confusion, hallucinations, panic, tremors, nausea, vomiting, diarrhea, stomach cramps, irregular heartbeat, rapid breathing, seizure (convulsions), and restless feeling followed by severe tiredness.

Phentermine and topiramate side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • pounding heartbeats or fluttering in your chest (even if you are resting);

  • sudden vision problems, sometimes with eye pain or redness;

  • trouble concentrating, problems with speech or memory;

  • a seizure (convulsions);

  • feeling very thirsty or hot, decreased sweating, hot and dry skin;

  • low blood sugar--headache, hunger, weakness, sweating, irritability, dizziness, or feeling jittery;

  • signs of metabolic acidosis--confusion, vomiting, lack of energy, irregular heartbeats; or

  • signs of a kidney stone--pain in your side or lower back, blood in your urine, painful or difficult urination.

Common side effects may include:

  • dizziness;

  • constipation;

  • numbness or tingly feeling;

  • sleep problems (insomnia); or

  • dry mouth, changes in your sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What are some things I need to know or do while I take Phentermine and Topiramate?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how phentermine and topiramate affects you.
  • Do not stop taking this medicine all of a sudden without calling your doctor. You may have a greater risk of seizures. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Avoid drinking alcohol while taking phentermine and topiramate.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • If you have high blood sugar (diabetes) and take drugs to lower blood sugar, talk with your doctor. Weight loss may raise the chance of low blood sugar if you take drugs to lower blood sugar. Call your doctor right away if you have signs of low blood sugar like dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating.
  • If you are being treated for high blood pressure, talk with your doctor. Weight loss may raise the chance of low blood pressure in people who are treated for high blood pressure. Call your doctor right away if you have signs of low blood pressure like very bad dizziness or passing out.
  • This medicine may cause an acid blood problem (metabolic acidosis). The chance may be higher in children and in people with kidney problems, breathing problems, or loose stools (diarrhea). The chance may also be higher if you take certain other drugs, if you have surgery, or if you are on a ketogenic diet. Over time, metabolic acidosis can cause kidney stones, bone problems, or growth problems in children. Talk with your doctor.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Follow the diet and workout plan that your doctor told you about.
  • If you take birth control, your monthly period (menstrual bleeding) may change while taking this medicine. Talk with your doctor if this happens.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant.
  • If you are a woman of childbearing age, take a pregnancy test 1 week before you start therapy and monthly while using phentermine and topiramate.
  • Use birth control that you can trust to prevent pregnancy while taking this medicine.
  • If you are pregnant or you get pregnant while taking phentermine and topiramate, call your doctor right away.

How do I store and/or throw out Phentermine and Topiramate?

  • Store at room temperature.
  • Keep lid tightly closed.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Index Terms

  • Phentermine/Topiramate
  • Qnexa
  • Topiramate and Phentermine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, extended release, oral:

Qsymia: 3.75/23: Phentermine 3.75 mg [immediate release] and topiramate 23 mg [extended release] [contains tartrazine]

Qsymia: 7.5/46: Phentermine 7.5 mg [immediate release] and topiramate 46 mg [extended release] [contains tartrazine]

Qsymia: 11.25/69: Phentermine 11.25 mg [immediate release] and topiramate 69 mg [extended release] [contains tartrazine]

Qsymia: 15/92: Phentermine 15 mg [immediate release] and topiramate 92 mg [extended release] [contains tartrazine]

Dietary Considerations

Take in the morning; avoid taking in the late evening. Most effective when combined with a low calorie diet, increased physical activity and behavior modification counseling.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Can increase resting heart rate; monitor closely when starting or increasing dosage, and in patients with cardiac or cerebrovascular disease. Reduce dose or discontinue use with a sustained increase in resting heart rate.

• CNS effects: Cognitive dysfunction and psychiatric disturbances (mood disorders including anxiety, depression or insomnia) may occur with use; incidence of cognitive events (including attention or memory difficulties) may be related to rapid titration and higher doses; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Risk may be increased in patients with a history of depression; dose reduction or discontinuation may be necessary.

• Glaucoma: Topiramate has been associated with acute myopia and secondary angle-closure glaucoma in adults and children, typically within 1 month of initiation but may occur at any time; discontinue in patients with acute onset of decreased visual acuity or ocular pain.

• Hyperthermia: Topiramate may be associated (rarely) with severe oligohidrosis and hyperthermia; use caution and monitor closely during strenuous exercise, during exposure to high environmental temperature, or in patients receiving other carbonic anhydrase inhibitors and drugs with anticholinergic activity.

• Hypokalemia: Can cause hypokalemia; use caution with concurrent use of hydrochlorothiazide or furosemide as risk of hypokalemia may be increased; monitor potassium closely.

• Hypotension: In hypertensive patients, weight loss in conjunction with antihypertensive therapy may increase the risk of hypotension; monitor blood pressure and adjust antihypertensive treatment as necessary.

• Metabolic acidosis (hyperchloremic, nonanion gap): May decrease serum bicarbonate concentrations, due to inhibition of carbonic anhydrase and increased renal bicarbonate loss. Risk may be increased in patients with conditions that predispose to acidosis (eg, diarrhea, ketogenic diet, renal disease, severe respiratory disorders, status epilepticus, surgery) or concurrent treatment with other carbonic anhydrase inhibitors. Monitor serum electrolytes and bicarbonate prior to and during treatment. Reduce dose or discontinue use if persistent metabolic acidosis develops.

• Renal calculus: Use is associated with kidney stone formation. Topiramate exhibits weak carbonic anhydrase inhibitory properties and may increase the risk of kidney stones. The risk of stones may be increased in patients on a ketogenic diet or concurrent treatment with other carbonic anhydrase inhibitors; risk of stones may be reduced by increasing fluid intake.

• Renal effects: May increase serum creatinine; peak increases from baseline were observed after 4-8 weeks of treatment. Monitor serum creatinine prior to and during treatment. For persistent elevations, dose reduction or discontinuation may be necessary.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Avoid use in patients with history of suicide attempts or current suicidal ideation. Monitor all patients for notable changes in behavior and discontinue use in patients who experience suicidal thoughts or new onset or worsening depression.

Disease-related concerns:

• Diabetes: Use with caution in patients with type 2 diabetes mellitus; antidiabetic agent requirements (eg, insulin or oral hypoglycemic agents) may be decreased with weight loss, anorexigens and concomitant dietary restrictions. Monitor blood glucose levels prior to and during treatment.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment may be required. Avoid use in patients with severe hepatic impairment (Child-Pugh class C).

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required.

Concurrent drug therapy issues:

• Sedatives: Avoid use with other sedative drugs or ethanol; CNS effects may be potentiated

Other warnings/precautions:

• Abuse potential: Phentermine is pharmacologically related to the amphetamines, which have a high abuse potential; prolonged use may lead to dependency. Prescriptions should be written for the smallest quantity consistent with good patient care to minimize the possibility of overdose.

• Withdrawal: Anticonvulsants (including topiramate) should not be discontinued abruptly because of the possibility of increasing seizure frequency. Therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Tapering doses over at least 1 week (1 dose every other day) is recommended.

Usual Adult Dose for Weight Loss

-Initial dose: Take one capsule of the lowest dose (phentermine 3.75 mg/topiramate 23 mg extended-release) orally once a day in the morning for the first 14 days.

-Maintenance dose: After 14 days, take one capsule of the recommended dose (phentermine 7.5 mg/topiramate 46 mg extended-release) orally once a day in the morning.

Comments:
-Weight loss should be evaluated after 12 weeks with phentermine 7.5 mg/topiramate 46 mg extended-release. If a patient has not lost at least 3% of baseline body weight, treatment discontinuation or dose escalation should be considered as it is unlikely the patient will achieve and sustain clinically meaningful weight loss at this dose.

Use: Adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese) OR 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia.

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