phentermine and topiramate

Action and Spectrum

Actions and spectrum: 

phentermine and topiramate is a combination medication used for weight loss. phentermine suppresses appetite, while topiramate is an anticonvulsant that increases satiety and reduces food cravings. Together, they work to promote weight loss by reducing food intake and increasing energy expenditure. 

The combination medication is indicated for use in adults having a BMI of 30 or higher (obese) or a BMI of 27 or greater (overweight) with at least one weight-related comorbidity such as hypertension, diabetes, or dyslipidemia. phentermine and topiramate have a broad spectrum of activity, as it targets multiple pathways that are involved in appetite regulation and energy metabolism.

The medication is thought to reduce appetite by increasing the release of neurotransmitters such as norepinephrine and serotonin, which suppress hunger and promote satiety. topiramate is believed to work by affecting neurotransmitters in the brain that regulate appetite and mood, as well as by reducing the hedonic pleasure associated with eating. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Metabolic acidosis (6.4-12.8%) 

Dry mouth (6.7-19.1%) 

Headache (7-10.6%) 

Constipation (7.9-16.1%) 

Paresthesia (4.2-19.9%) 

URI (12.2-15.8%) 

Nasopharyngitis (9.4-12.5%)  

1-10% 

Dysgeusia (1.3-9.4%) 

Increased creatinine (2.1-8.4%) 

Nausea (3.6-7.2%) 

Back pain (5.4-6.6%) 

Blurred vision (4-6.3%) 

UTI (3.3-5.2%)
Cough (3.3-4.8%) 

Anxiety (1.8-4.1%) 

Alopecia (1.7-3.7%) 

attention deficit (0.4-3.5%) 

Extremity pain (2.1-3%) 

Muscle spasms (2.8-2.9%) 

Sinus congestion (2-2.6%) 

Pharyngeal pain (1.2-2.5%) 

Gastroenteritis (0.8-2.5%) 

Palpitations (0.8-2.4%) 

Neck pain (1.2-2.2%) 

Decreased appetite (1.5-2.1%) 

Dysmenorrhea (0.4-2.1%) 

Thirst (1.8-2%) 

Insomnia (5-9.4%) 

Dizziness (2.9-8.6%) 

Sinusitis (6.8-7.8%) 

Bronchitis (4.4-6.7%) 

Diarrhea (5-6.4%) 

Fatigue (4.4-5.9%) 

Hypokalemia (0.4-4.9%) 

Depression (2.8-4.3%) 

Irritability (1.7-3.7%) 

Hypoesthesia (0.8-3.7%) 

GERD (0.8-3.2%) 

Musculoskeletal pain (0.8-3%) 

Dyspepsia (2.1-2.8%) 

Rash (1.7-2.6%) 

Dry eye (0.8-2.5%) 

Hypokalemia (0.4-2.5%) 

Eye pain (2.1-2.2%) 

Oral paresthesia (0.2-2.2%) 

Nephrolithiasis (0.2-1.2%) 

Chest discomfort (0.2-2.1%) 

Nasal congestion (1.2-2%)  

Post marketing Reports 

phentermine 

• CNS: psychosis, Euphoria, tremor 
• Allergic: Urticaria 
• Reproductive: impotence, Changes in libido 
• Cardiovascular: ischemic events, Increased blood pressure

Topiramate 

• Dermatologic: Bullous skin reactions 
• Hepatic: hepatitis, Hepatic failure 
• Ophthalmic: angle closure glaucoma, Maculopathy, increased intraocular pressure 
• Central nervous system: ideation and Suicidal behavior 
• Gastrointestinal: Pancreatitis 
• Metabolic: Hypothermia, hyperammonemia 

Black Box Warning

Black Box Warning: 

phentermine and topiramate combination have a black box warning for an increased risk of suicidal ideation or behaviour. Patients should be monitored for suicidal thoughts or behaviour and appropriate measures should be taken.

The combination may also cause an increased heart rate, which can increase the risk of cardiovascular events. Therefore, patients with a history of cardiovascular disease or stroke should use this combination with caution. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity to sympathomimetic amines or topiramate 
• Hyperthyroidism 
• Glaucoma 
• Pregnancy or breastfeeding 
• History of metabolic acidosis, such as diabetic ketoacidosis 
• Concurrent use of MAO inhibitors or within 14 days of stopping MAOIs 
• Severe renal impairment 
• Severe hepatic impairment

Caution: 

• Cardiovascular disease: phentermine and topiramate can increase heart rate and blood pressure, which may be problematic in individuals with a history of heart disease, stroke, or other cardiovascular conditions. 
• Glaucoma: topiramate can increase intraocular pressure, which may worsen symptoms of glaucoma. 
• Metabolic acidosis: topiramate can cause metabolic acidosis, which is a condition where the body produces too much acid or loses too much bicarbonate. 
• Mood disorders: topiramate can cause mood changes, including depression, anxiety, and suicidal thoughts. 
• Pregnancy and breastfeeding: phentermine and topiramate are classified as pregnancy category X and should not be used during pregnancy or breastfeeding. 
• Renal impairment: phentermine and topiramate should be used with caution in individuals with renal impairment as their clearance is decreased in such cases. 
• Alcohol use: phentermine and topiramate can enhance the effects of alcohol, so patients should avoid alcohol while taking these medications.

Comorbidities: 

phentermine and topiramate are used for the treatment of obesity and weight management in patients having a body mass index of 30 kg/m² or greater or in patients with a BMI of 27 kg/m² or greater with at least one weight-related comorbidity such as type 2 diabetes, hypertension, or dyslipidemia.

The medication should be used under caution in patients with suicidal thoughts or behaviour, depression, or other mental health disorders, as topiramate have an increased risk of suicidal thoughts and behaviour. It should also be used under caution in patients with a history of kidney stones or glaucoma, as topiramate may increase the risk of these conditions. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: It is not known whether phentermine and topiramate is excreted in human milk.  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

phentermine is a sympathomimetic amine, which works by suppressing appetite and increasing energy expenditure through its actions on the central nervous system. It stimulates the release of norepinephrine, dopamine, and serotonin in the brain, which leads to decreased appetite and increased metabolism. 

topiramate, on the other hand, is an anticonvulsant that works by enhancing the activity of gamma-aminobutyric acid (GABA) in the brain. It is believed to reduce appetite and increase satiety through its effects on the hypothalamus and other brain areas involved in the regulation of appetite. 

The combination of phentermine and topiramate is thought to produce a greater weight loss effect than either drug alone due to their complementary mechanisms of action.  

Pharmacodynamics: 

phentermine and topiramate have different mechanisms of action, but they work together to produce weight loss in patients. 

phentermine is a sympathomimetic amine that acts by stimulating the release of norepinephrine in the central nervous system, which decreases appetite and increases energy expenditure. 

topiramate is an antiepileptic drug that also has weight loss effects. The mechanism of action is not fully known, but it is believed to work by enhancing the activity of gamma-aminobutyric acid (GABA) in the brain, which can decrease appetite and promote feelings of fullness. 

Together, phentermine and topiramate work to decrease appetite, increase energy expenditure, and promote feelings of fullness, leading to weight loss in patients.  

Pharmacokinetics: 

phentermine: 

• Absorption: phentermine is readily absorbed after oral administration, with peak plasma concentrations occurring in 3 to 4.4 hours. 
• Distribution: phentermine is widely distributed throughout the body, including the brain and breast milk. 
• Metabolism: phentermine is primarily metabolized by the liver through CYP3A4-mediated oxidation to inactive metabolites. 
• Elimination and excretion: phentermine and its metabolites are excreted in the urine, with a small amount excreted in the feces. 

topiramate: 

• Absorption: topiramate is rapidly and completely absorbed after oral administration, with peak plasma concentrations occurring in 2 to 3 hours. 
• Distribution: topiramate is widely distributed throughout the body, including the brain and breast milk. 
• Metabolism: topiramate is minimally metabolized and primarily eliminated unchanged in the urine. 
• Elimination and excretion: topiramate are eliminated from the body by renal excretion, with a half-life of approximately 21 hours. 

Adminstartion

Administration: 

phentermine and topiramate is an oral medication that is usually administered once daily, with or without food. The dose may be increased gradually over time, as directed by a healthcare provider.

The tablets should be administered whole and not crushed, chewed, or broken. It is recommended to avoid taking this medication late in the day to prevent insomnia. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: phentermine and topiramate 

Pronounced: [ FEN-ter-meen-and-toe-PIR-a-mate]  

Why do we use phentermine and topiramate? 

phentermine and topiramate is a combination medication used for weight loss in overweight adults or obese who have weight-related health problems such as high blood pressure, diabetes, or high cholesterol. It is intended to be used as part of a weight loss program that includes dietary changes and increased physical activity.

phentermine and topiramate can help reduce appetite and increase feelings of fullness, which may lead to decreased food intake and weight loss. It is also being investigated for its potential use in the treatment of binge eating and obstructive sleep apnea.