Phentermine and Topiramate

Phentermine and topiramate is approved to help people lose and maintain weight when used alongside a reduced-calorie diet and increased physical activity. Specific approvals depend on the product:

• Phentermine and Topiramate Extended-Release (capsule) is approved for adults with obesity
• Phentermine and Topiramate Extended-Release (capsule) is approved for adults who are overweight and have at least one weight-related health condition
• Qsymia (extended-release capsule) is approved for adults and adolescents aged 12 and older with obesity
• Qsymia is also approved for adults who are overweight with at least one weight-related health condition
• Phentermine and topiramate (generic extended-release capsule) is approved for adults and adolescents aged 12 and older with obesity
• Phentermine and topiramate (generic extended-release capsule) is also approved for adults who are overweight with at least one weight-related health condition
• The effect of these medications on heart disease risk or mortality has not been established
• Safety and effectiveness when combined with other weight-loss products — prescription, over-the-counter, or herbal — have not been established

This medication pairs two ingredients with different but complementary effects. Phentermine is a stimulant-type drug that triggers the release of brain chemicals called catecholamines, which reduce appetite and food intake. Topiramate's exact mechanism for weight loss is not fully known, but it appears to work by suppressing appetite and enhancing the feeling of fullness through several effects on the brain, including boosting a calming neurotransmitter (GABA), blocking certain excitatory brain receptors, and inhibiting an enzyme called carbonic anhydrase.

These extended-release capsules are taken once every morning by mouth, with or without food. Evening doses should be avoided because the medication can interfere with sleep. Treatment starts at a low dose for the first two weeks, then increases step by step based on how the body responds — your prescriber will guide this schedule. If you need to stop the highest dose, it must be tapered gradually over at least a week rather than stopped all at once, to lower the risk of seizures.

• Take in the morning — not in the evening
• Can be taken with or without food
• Dose is adjusted based on weight loss in adults, or BMI change in adolescents aged 12 and older
• Never stop the highest dose abruptly; follow your prescriber's tapering plan

The most common side effects in adults include tingling or numbness (especially in the hands, feet, or face), dry mouth, constipation, dizziness, insomnia, metallic or altered taste, headache, and nausea. In adolescents aged 12 and older, commonly reported effects include depression, dizziness, joint pain, fever, flu, and ligament sprains, as well as tingling. This medication also tends to increase heart rate, which your doctor will monitor.

• Tingling or numbness (paraesthesia)
• Dry mouth
• Constipation
• Dizziness
• Insomnia (trouble sleeping)
• Altered or metallic taste (dysgeusia)
• Headache
• Nausea
• Increased heart rate
• Mood changes, anxiety, or depression
• Memory, concentration, or word-finding difficulties

Contact your doctor right away for thoughts of suicide or self-harm, sudden vision changes or eye pain, signs of acid buildup in the blood (rapid breathing, fatigue, confusion), serious skin reactions, or swelling of the face or throat.

• Pregnancy and birth defects: This medication can cause serious birth defects, particularly cleft lip or palate. It must not be taken during pregnancy. Anyone who can become pregnant must use reliable contraception and get a pregnancy test before starting and every month during treatment. The medication is dispensed only through a special restricted pharmacy program (REMS).
• Suicidal thoughts and mood changes: Topiramate, an anti-seizure drug in this combination, is associated with increased risk of suicidal thoughts or behavior. All patients should be monitored for new or worsening depression or unusual mood shifts. Avoid this medication if you have a history of suicidal thoughts or attempts.
• Eye problems: A rare but serious eye condition involving sudden blurred vision, eye pain, and acute glaucoma (high eye pressure) has been reported, usually within the first month of use. Stop the medication immediately and seek care if this occurs.
• Metabolic acidosis: This medication can cause a drop in blood bicarbonate (a buildup of acid in the blood), which may cause rapid breathing, fatigue, or in severe cases, heart rhythm problems. Blood chemistry should be checked before and during treatment.
• Reduced kidney function: Serum creatinine (a marker of kidney health) may rise during treatment. Kidney function should be monitored regularly.
• Seizure risk on abrupt stopping: Stopping the highest dose suddenly may trigger a seizure. Always taper the dose gradually under medical supervision.
• Slowed growth in adolescents: In teens aged 12–17, this medication is associated with reduced height gain and less bone mineral density buildup. Height should be monitored throughout treatment.
• Cognitive effects: Memory problems, difficulty concentrating, and trouble finding words can occur. Use caution when driving or operating machinery until you know how the medication affects you.

Several important interactions can occur with this medication — be sure your prescriber and pharmacist know everything you take:

• MAO inhibitors (MAOIs): Combining phentermine with MAOIs can cause a dangerous spike in blood pressure (hypertensive crisis). Do not use together or within 14 days of stopping an MAOI.
• Alcohol and CNS depressants (sedatives, benzodiazepines, sleep aids): Increase dizziness, drowsiness, and impaired thinking. Avoid excessive alcohol.
• Other carbonic anhydrase inhibitors: Combining them with topiramate worsens metabolic acidosis and raises the risk of kidney stones. Avoid if possible.
• Non-potassium-sparing diuretics (water pills): Increase the risk of low potassium levels (hypokalemia). Potassium should be monitored.
• Valproic acid: Can raise ammonia levels in the blood and may cause abnormally low body temperature when combined with topiramate.
• Oral contraceptives: Topiramate may alter hormone levels and cause irregular spotting. Do not stop your contraceptive — tell your doctor if spotting is concerning.
• Amitriptyline: Topiramate can increase blood levels of this antidepressant; dose adjustments should be based on clinical response.
• Pioglitazone: Topiramate may reduce the effectiveness of this diabetes medication; blood sugar should be monitored more closely.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Pregnancy: Do not take this medication if you are pregnant. It causes serious fetal harm, including cleft lip and palate. Use effective contraception throughout treatment.
• Breastfeeding: Breastfeeding is not recommended while taking this medication.
• Glaucoma: Do not take if you have glaucoma (a condition of elevated eye pressure).
• Hyperthyroidism (overactive thyroid): Do not take if you have this condition.
• MAOI use: Do not take within 14 days of stopping a monoamine oxidase inhibitor.
• Allergy: Do not take if you have a known allergy to phentermine, topiramate, or any ingredient in the capsule.
• Kidney impairment: Dose should not exceed a moderate level in patients with moderate or severe kidney disease; the medication has not been studied in people on dialysis.
• Liver impairment: Dose should not exceed a moderate level in patients with moderate liver impairment.
• History of depression or suicidal thoughts: Use with caution; avoid if there is a history of active suicidal ideation or past suicide attempts.
• Adolescents aged 12–17: Monitor height, bone growth, and weight loss rate regularly during treatment.

Taking too much phentermine and topiramate can be serious. Phentermine overdose may cause restlessness, tremor, rapid breathing, confusion, hallucinations, high or low blood pressure, and irregular heartbeat. Too much topiramate can cause severe metabolic acidosis, drowsiness, speech problems, blurred vision, confusion, seizures, and low blood pressure. Deaths have been reported with topiramate overdose. If you suspect an overdose, call the Poison Help line at 1-800-222-1222 or seek emergency medical care immediately.

Phentermine acts similarly to amphetamines, stimulating the central nervous system and potentially raising blood pressure, though the combination product did not show a blood pressure–raising (pressor) effect in clinical studies. In fact, at the highest approved dose, it was associated with a modest reduction in systolic blood pressure compared to placebo, while mildly increasing heart rate. The medication can temporarily reduce how well the kidneys filter blood (glomerular filtration rate), but this effect appears to reverse after stopping treatment.

Both phentermine and topiramate are absorbed from the gut and can be taken with or without food — a high-fat meal does not meaningfully change how either drug is absorbed. Phentermine has a half-life of about 20 hours, meaning it takes roughly 20 hours for the body to clear half of the dose. Topiramate has a much longer half-life of about 65 hours. Both drugs are eliminated primarily through the urine in largely unchanged form. People with kidney disease clear both drugs more slowly, leading to higher drug levels, which is why dose limits apply in moderate and severe kidney impairment.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) . protect from moisture.