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Phentermine


General


Pronunciation

(FEN ter meen)


Brand Names: U.S.

  • Adipex-P
  • Suprenza [DSC]

Indications


Use: Labeled Indications

Short-term (few weeks) adjunct therapy in obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, diabetes, hyperlipidemia, controlled hypertension); therapy should be used in conjunction with a comprehensive weight management program.


Contraindications


Hypersensitivity or idiosyncrasy to phentermine or other sympathomimetic amines or any component of the formulation; history of cardiovascular disease (arrhythmias, congestive heart failure, coronary artery disease, stroke, uncontrolled hypertension); hyperthyroidism, glaucoma, agitated states, history of drug abuse; use during or within 14 days following MAO inhibitor therapy; pregnancy, breast-feeding


Dosing and Administration


Dosing: Adult

Note: Dosing is presented in terms of the salt, phentermine hydrochloride (not as phentermine base).

Obesity (short-term adjunct): Oral:

Capsule, tablet: 15-37.5 mg daily given in 1-2 divided doses. Individualize to achieve adequate response with lowest effective dose.

Orally disintegrating tablet (ODT): One tablet (15-37.5 mg daily) every morning. Individualize to achieve adequate response with lowest effective dose.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Children >16 years: Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment provided in manufacturers labeling (has not been studied). Phentermine is excreted in the urine and systemic exposure may be increased in renal impairment; use with caution.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling (has not been studied).


Administration

Avoid late evening administration.

Capsules, tablets: Administer before breakfast or 1-2 hours after breakfast. Tablets may be divided in half and dose may be given in 2 divided doses.

Orally disintegrating tablets (Suprenza): With dry hands, place tablet on the tongue and allow to dissolve, then swallow with or without water. May administer with or without food.


Dietary Considerations

Capsules, tablets: Should be taken before breakfast or 1-2 hours after breakfast; avoid taking in the late evening. Most effective when combined with a low-calorie diet and behavior modification counseling.


Storage

Store at controlled room temperature of 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

Adipex-P: 37.5 mg

Generic: 15 mg, 30 mg, 37.5 mg

Tablet, Oral, as hydrochloride:

Adipex-P: 37.5 mg [scored; contains brilliant blue fcf (fd&c blue #1)]

Generic: 37.5 mg

Tablet Dispersible, Oral, as hydrochloride:

Suprenza: 15 mg [DSC] [contains fd&c blue #1 aluminum lake, fd&c yellow #5 aluminum lake]

Suprenza: 30 mg [DSC] [contains fd&c yellow #5 aluminum lake]

Suprenza: 37.5 mg [DSC] [contains fd&c blue #1 aluminum lake]


Drug Interactions

Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Avoid combination

Alcohol (Ethyl): May enhance the adverse/toxic effect of Phentermine. Monitor therapy

Alkalinizing Agents: May decrease the excretion of Amphetamines. Consider therapy modification

Ammonium Chloride: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Analgesics (Opioid): Amphetamines may enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Antacids: May decrease the excretion of Amphetamines. Monitor therapy

Antihistamines: Amphetamines may diminish the sedative effect of Antihistamines. Monitor therapy

Antihypertensive Agents: Amphetamines may diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents: May diminish the stimulatory effect of Amphetamines. Monitor therapy

Ascorbic Acid: May decrease the serum concentration of Amphetamines. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Carbonic Anhydrase Inhibitors: May decrease the excretion of Amphetamines. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Ethosuximide: Amphetamines may diminish the therapeutic effect of Ethosuximide. Amphetamines may decrease the serum concentration of Ethosuximide. Monitor therapy

Gastrointestinal Acidifying Agents: May decrease the serum concentration of Amphetamines. Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Amphetamines may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Lithium: May diminish the stimulatory effect of Amphetamines. Monitor therapy

MAO Inhibitors: May enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Tedizolid. Avoid combination

Methenamine: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Monitor therapy

Multivitamins/Fluoride (with ADE): May decrease the serum concentration of Amphetamines. More specifically, the ascorbic acid (vitamin C) in many multivitamins may decrease amphetamine concentrations. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Amphetamines. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Amphetamines. Specifically, vitamin C may impair absorption of amphetamines. Monitor therapy

PHENobarbital: Amphetamines may decrease the serum concentration of PHENobarbital. Monitor therapy

Phenytoin: Amphetamines may decrease the serum concentration of Phenytoin. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy

Urinary Acidifying Agents: May decrease the serum concentration of Amphetamines. Monitor therapy


Monitoring Parameters

Weight, waist circumference; blood pressure


Lab Test Interferences


Test Interactions

May interfere with urine detection of amphetamines/methamphetamines (false-positive).


Adverse Reactions


Frequency not defined.

Cardiovascular: Hypertension, ischemic events, palpitation, primary pulmonary hypertension and/or regurgitant cardiac valvular disease, tachycardia

Central nervous system: Dizziness, dysphoria, euphoria, headache, insomnia, overstimulation, psychosis, restlessness

Dermatologic: Urticaria

Endocrine & metabolic: Changes in libido

Gastrointestinal: Constipation, diarrhea, unpleasant taste, xerostomia

Genitourinary: Impotence

Neuromuscular & skeletal: Tremor


Warnings/Precautions


Special Populations: Renal Function Impairment

Exposure increases can be expected in patients with renal impairment.


Warnings/Precautions

Concerns related to adverse effects:

- CNS effects: Amphetamines may impair the ability to engage in potentially hazardous activities (eg, operating machinery or driving).

- Primary pulmonary hypertension (PPH): A rare, frequently fatal disease of the lungs, PPH has been reported to occur in patients receiving a combination of phentermine and fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of phentermine alone cannot be ruled out; rare cases of PPH have been reported in patients taking phentermine alone. Discontinue in patients experiencing new-onset dyspnea, chest pain, syncope, or lower extremity edema.

- Valvular heart disease: Serious regurgitant cardiac valvular disease (primarily affecting the mitral, aortic, and/or tricuspid valves) has been reported to occur in patients receiving a combination of phentermine and fenfluramine or dexfenfluramine. The possibility of an association between valvular heart disease and the use of phentermine alone cannot be ruled out; rare cases of valvular heart disease have been reported in patients taking phentermine alone.

Disease-related concerns:

- Cardiovascular disease: Avoid stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could increase the risk of sudden death that these conditions alone carry.

- Diabetes: Use with caution in patients with diabetes mellitus; antidiabetic agent requirements (eg, insulin or oral hypoglycemic agents) may be decreased with anorexigens and concomitant dietary restrictions.

- Hypertension: Use with caution in patients with mild hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate.

- Renal impairment: Use caution in patients with renal impairment; use has not been studied; however, an increase in exposure is expected in renal impairment.

- Seizure disorders: Avoid or use with caution in patients with history of seizures (Apovian, 2015).

- Tourettes syndrome: Use with caution in patients with Tourette's syndrome; stimulants may unmask tics.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Elderly: Use caution in this age group due to the risk for causing dependence, hypertension, angina, and myocardial infarction.

Dosage form specific issues:

- Tartrazine (FDC yellow #5): Some products may contain tartrazine which may cause allergic reactions in patients with sensitivity (caution in patients with asthma or aspirin hypersensitivity).

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 possibility of overdose.

- Appropriate use: Phentermine is not approved for long-term use. Clinicians should carefully examine the potentially benefits against potential risks associated with use of medications in this class. Consult weight loss guidelines for current pharmacotherapy recommendations.

- Tolerance: Tolerance to the anorectic effect usually develops within a few weeks; discontinue use when tolerance develops, do not exceed recommended dosage in an attempt to overcome tolerance.


Pregnancy Risk Factor

X


Pregnancy Considerations

Use is contraindicated during pregnancy (lack of potential benefit and possible fetal harm). The risks of using appetite suppressing drugs in pregnant women are not known (NHLBI 1998) and limited information is available about the use of phentermine in pregnancy (Jones 2002; McElhatton 2006). Weight loss therapy is generally not recommended for pregnant women. Obese and overweight women should be encouraged to participate in weight reduction programs prior to attempting pregnancy; weight gain during pregnancy should be determined by their prepregnancy BMI and current guidelines (ACOG 2013; ADA 2009).


Actions


Pharmacology

Phentermine is a sympathomimetic amine with pharmacologic properties similar to the amphetamines. The mechanism of action in reducing appetite appears to be secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine.


Absorption

Well absorbed. Rate and extent of exposure of orally disintegrating tablets (ODT) are equivalent to capsules and tablets administered under fasting conditions. Administration of the ODT after a high-fat/high-calorie breakfast decreased Cmax by ~5% and AUC by ~12%.


Distribution

Vd: 348 L


Metabolism

Hepatic via p-hydroxylation (aromatic ring) and N-oxidation (alipthatic side chain); primarily metabolized by CYP3A4 (but does not show extensive metabolism).


Excretion

Primarily urine (62% to 85% as unchanged drug)


Time to Peak

3 to 4.4 hours


Half-Life Elimination

~20 hours


Protein Binding

17.5%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience anxiety, constipation, diarrhea, dry mouth, insomnia, bad taste, decreased libido, sexual dysfunction, or agitation. Have patient report immediately to prescriber behavioral changes, angina, tachycardia, arrhythmia, mood changes, tremors, shortness of breath, swelling of arms or legs, severe dizziness, passing out, or severe headache (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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