Medications> Obesity>

INDICATIONS

• Short-term (a few weeks) management of obesity (in adjunct to weight reduction program of exercise, behavioral modification and caloric restriction) in patients with an initial BMI > 30 kg/m2, or BMI > 27 kg/m2 in the presence of other risk factors (e.g., hypertension, diabetes, hyperlipidemia).

MECHANISM

• Sympathomimetic amine with pharmacologic properties similar to the amphetamines.
• Mechanism of action in reducing appetite appears to be secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine.

USUAL ADULT DOSING

• Oral: 18.75-37.5 mg/ day (phentermine hydrochloride) or 15-30 mg/day (phentermine resin)
• Administer before breakfast or 1-2 hours after breakfast.
• To decrease insomnia, phentermine should be administered 10-14 hours before bedtime.

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

• Use lower doses in patients with decreased renal function.

• Use with caution, consider lower doses with decreased hepatic function.

• Category C.

• Avoid due to potential for serious adverse reactions in nursing infant.

ADVERSE DRUG REACTIONS

• Compared to amphetamines, phentermine causes less euphoriant properties and causes less central nervous system or cardiovascular toxicity.

• Palpitations, tachycardia, elevation of blood pressure.
• CNS: overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache.

• Genitourinary/endocrine: impotence; changes in libido.
• GI: dry mouth; unpleasant taste; diarrhea; constipation.
• Dermatologic: allergic urticaria.

• Primary pulmonary hypertension (PPH) most commonly reported with concurrent use of phentermine with fenfluramine or dexfenfluramine, but rare reports of PPH have been reported in patients taking phentermine alone.
• Valvular heart disease: serious regurgitant cardiac valvular disease affecting the mitral, aortic and/or tricuspid valves reported with concurrent use of phentermine with fenfluramine or dexfenfluramine, but rare reports of valvular heart disease have been reported with phentermine alone.
• Psychosis (associated with doses above the recommended range)

DRUG INTERACTIONS

• Guanethidine, guanadrel, methyldopa, and reserpine: May decrease hypotensive effect of these agents.
• MAOIs (eg, phenelzine); furazolidone: May cause hypertensive crisis and intracranial hemorrhage. Phentermine should not be administered during or within 14 days following the use of MAOIs or drugs with MAO-inhibiting activity.
• Selective serotonin reuptake inhibitors (eg, fluoxetine): Sympathomimetic effects of phentermine and risk of serotonin syndrome may be increased. Avoid co-administration.
• Tricyclic Antidepressant: Pressor response to phentermine may be exaggerated. Avoid co-administration.
• Phenothiazines: Efficacy of phentermine may be decreased. Avoid co-administration if possible.
• Any agents with sympathomimetic properties (e.g amphetamine, dextroamphetamine, ephedra alkaloids, Ma huang) may result in additive sympathomimetic side effects (e.g hypertensive crisis, cardiac arrhythmias, severe agitation) may occur. Avoid co-administration.

PHARMACOKINETIC

COMMENTS

• Contraindicated in patients with advanced arteriosclerosis, cardiovascular disease, moderate to severe hypertension, hyperthyroidism, and glaucoma.
• Drug dependence: Psychological and physical dependence may occur with continued use; this class of drugs has been extensively abused.
• Avoid in patients with history of drug abuse.
• Compared to amphetamine products, phentermine produces the same degree of weight loss, but causes less euphoriant properties and central nervous system or cardiovascular toxicity.
• Tolerance to the anorexiant effects of phentermine develops within a few weeks of therapy. Dose may be increased to a maximum of 37.5 mg/d, but phentermine should be discontinued if tolerance develops to the maximum recommended dose.
• Use with caution in patients with diabetes mellitus; antidiabetic agent requirements may be altered with anorexigens and concomitant dietary restrictions.
• Average weight loss at 6 months is 3.6 kg compared to placebo.
• Currently being studied as a combination drug with Topiramate. When used at low doses, may have synergistic effects.

REFERENCES