Phentermine + Topiramate

Indications

Phentermine + Topiramate is used for: Obesity

Adult Dose

Obesity Indicated as an adjunct to a reduced-calorie diet and exercise for chronic weight management in adults with an initial BMI ?30 kg/m² (obese), or BMI ?27 kg/m² (overweight) in the presence of at least 1 weight related comorbidity (eg, hypertension, type 2 diabetes mellitus, dyslipidemia) Initial: 3.75 mg/23 mg PO qDay for 14 days, THEN Day 15: Increase to 7.5 mg/46 mg PO qDay for 12 weeks, then evaluate weight loss If a patient has not lost at least 3% of baseline body weight on 7.5 mg/46 mg, discontinue or escalate dose, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss at the 7.5 mg/46 mg dose To escalate the dose: Increase to 11.25 mg/69 mg PO qDay for 14 days; followed by dosing 15 mg/92 mg qDay; evaluate weight loss following dose escalation to 15 mg/92 mg after an additional 12 weeks of treatment If a patient has not lost at least 5% of baseline body weight on 15 mg/92 mg, discontinue as directed (ie, gradually), as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment Note: 3.75 mg/23 mg and 11.25 mg/69 mg dosage strengths are for titration purposes only Hepatic impairment Mild (Child-Pugh 5-6): No dose adjustment required Moderate (Child-Pugh 7-9): Not to exceed 7.5 mg/46 mg qDay Severe (Child-Pugh 10-15): Avoid use

Child Dose

Renal Dose

Renal impairment Mild (>50 mL/min): No dose adjustment required Moderate (30-49 mL/min) and severe (<30 mL/min): Not to exceed 7.5 mg/46 mg qDay

Administration

Take once daily in the morning with or without food Avoid dosing in the evening due to the possibility of insomnia Discontinue 15 mg/92 mg gradually by taking a dose every other day for at least 1 week prior to stopping treatment altogether, due to the possibility of precipitating a seizure

Contra Indications

Hypersensitivity or idiosyncrasy to sympathomimetic amines Pregnancy Glaucoma Hyperthyroidism Use of phentermine is contraindicated during or within 14 days following MAOIs due to risk for hypertensive crisis

Precautions

May increase resting heart rate up to 20 bpm; caution in patients with history of cardiac or cerebrovascular disease Antiepileptic drugs (AEDs), including topiramate, increase the risk of suicidal thoughts or behavior Acute myopia associated with secondary angle closure glaucoma has been reported with topiramate; monitor for increased IOP due to risk of permanent loss of vision May cause mood disorders, including depression, and anxiety, as well as insomnia; patient with history of depression may be at increased risk of recurrent depression or other mood disorders Cognitive dysfunction (eg, impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties) reported; rapid titration or high initial doses may be associated with higher rates Hyperchloremic, nonanion gap, and metabolic acidosis reported Increase in serum creatinine that reflects a decrease in renal function (glomerular filtration rate) reported; peak increases were observed in clinical trials after 4-8 weeks of treatment and gradually declined but remained elevated over baseline values Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues; monitor for needed diabetic therapy adjustments In patients treated for hypertension, weight loss may increase the risk of hypotension; monitor for needed antihypertensive dose adjustments Use with combination oral contraceptives may increase frequency of irregular bleeding/spotting; need not discontinue unless spotting is trouble to patient

Pregnancy-Lactation

Pregnancy Category: X Can cause fetal harm and weight loss offers no potential benefit to a pregnant woman Lactation: Distributed in breast milk; because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug

Interactions

Adverse Effects

Side effects of Phentermine + Topiramate : >10% Paresthesia (4.2-19.9%) Dry mouth (6.7-19.1%) Constipation (7.9-16.1%) URI (12.2-15.8%) Metabolic acidosis (6.4-12.8%) Nasopharyngitis (9.4-12.5%) Headache (7-10.6%) 1-10% Insomnia (5-9.4%) Dysgeusia (1.3-9.4%) Dizziness (2.9-8.6%) Increased serum creatinine (2.1-8.4%) Sinusitis (6.8-7.8%) Nausea (3.6-7.2%) Bronchitis (4.4-6.7%) Back pain (5.4-6.6%) Diarrhea (5-6.4%) Blurred vision (4-6.3%) Fatigue (4.4-5.9%) UTI (3.3-5.2%) Hypokalemia (persistent) (0.4-4.9%) Cough (3.3-4.8%) Depression (2.8-4.3%) Anxiety (1.8-4.1%) Irritability (1.7-3.7%) Alopecia (1.7-3.7%) Hypoesthesia (0.8-3.7%) Disturbance in attention (0.4-3.5%) GERD (0.8-3.2%) Extremity pain (2.1-3%) Musculoskeletal pain (0.8-3%) Muscle spasms (2.8-2.9%) Dyspepsia (2.1-2.8%) Sinus congestion (2-2.6%) Rash (1.7-2.6%) Pharyngeal pain (1.2-2.5%) Dry eye (0.8-2.5%) Gastroenteritis (0.8-2.5%) Hypokalemia (acute) (0.4-2.5%) Palpitations (0.8-2.4%) Eye pain (2.1-2.2%) Neck pain (1.2-2.2%) Oral paresthesia (0.2-2.2%) Decreased appetite (1.5-2.1%) Nephrolithiasis (0.2-1.2%) Dysmenorrhea (0.4-2.1%) Chest discomfort (0.2-2.1%) Thirst (1.8-2%) Nasal congestion (1.2-2%)

Mechanism of Action

Phentermine: Sympathomimetic amine; induces anorectic effect via release of norepinephrine in the hypothalamus causing appetite suppression by increasing blood leptin concentration; exact mechanism of action unknown Topiramate: Effect may be through appetite suppression and satiety enhancement that is induced by a combination of pharmacologic effects including augmenting neurotransmitter gamma-aminobutyrate activity, voltage-gated ion channels modulation, AMPA/kainite excitatory glutamate receptor inhibition, or carbonic anhydrase inhibition