Phentermine

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 [contains brilliant blue fcf (fd&c blue #1), corn starch]

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

Lomaira: 8 mg [scored; contains brilliant blue fcf (fd&c blue #1), corn starch]

Generic: 37.5 mg

Tablet Disintegrating, 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]

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

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 C_max by ~5% and AUC by ~12%.

Distribution

V_d: 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%

Use in Specific Populations

Special Populations: Renal Function Impairment

Exposure increases can be expected in patients with renal impairment.

Use: Labeled Indications

Obesity (short-term adjunct): Short-term (few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity 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).

Contraindications

Hypersensitivity or idiosyncrasy to phentermine, other sympathomimetic amines or any component of the formulation; history of cardiovascular disease (eg, arrhythmias, 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

Dosage and Administration

Dosing: Adult

Note: Suprenza has been discontinued in the US for more than 1 year.

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

Obesity (short-term adjunct): Oral:

Capsule, tablet (excluding Lomaira): 15 to 37.5 mg/day in 1 to 2 divided doses. Individualize to achieve adequate response with lowest effective dose.

Tablet (Lomaira only): 8 mg 3 times daily. Individualize to achieve adequate response with lowest effective dose.

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Obesity (short-term adjunct): Adolescents >16 years: Refer to adult dosing.

Administration

Avoid late evening administration. Most effective when combined with a low-calorie diet and behavior modification counseling.

Capsules, tablets (excluding Lomaira): Administer before breakfast or 1 to 2 hours after breakfast. Tablets may be divided in half and dose may be given in 2 divided doses.

Tablet (Lomaira only): Administer 30 minutes before meals. Tablets are scored and may be divided in half.

Orally disintegrating tablets (ODT): 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 (excluding Lomaira): Should be taken before breakfast or 1 to 2 hours after breakfast.

Tablet (Lomaira only): Should be taken 30 minutes before meals.

Storage

Store at 20°C to 25°C (68°F to 77°F).

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. Management: Consider alternatives to using amphetamines and alkalinizing agents in combination. If these agents must be used together, patients should be monitored closely for excessive amphetamine effects. Consider therapy modification

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

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

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

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. 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

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Amphetamines. Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Amphetamines. Exceptions: FLUoxetine; PARoxetine. Monitor therapy

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

Esketamine: May enhance the hypertensive effect of CNS Stimulants. 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

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Iobenguane Radiopharmaceutical Products: Amphetamines may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Avoid combination

Iobenguane Radiopharmaceutical Products: CNS Stimulants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Avoid combination

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

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

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

Monoamine Oxidase 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. Avoid combination

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

Opioid Agonists: Amphetamines may enhance the analgesic effect of Opioid Agonists. Monitor therapy

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

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

Quinolones: Amphetamines may enhance the cardiotoxic effect of Quinolones. Monitor therapy

Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Amphetamines may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Amphetamines. Management: Monitor for increased amphetamine toxicities, including signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability) when these agents are combined. Monitor therapy

Serotonergic Agents (High Risk): Amphetamines may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Amitriptyline; Amoxapine; ClomiPRAMINE; Desipramine; Dothiepin; Doxepin (Systemic); Doxepin (Topical); FLUoxetine; Imipramine; Isocarboxazid; Linezolid; Lofepramine; Melitracen [INT]; Methylene Blue; Moclobemide; Nortriptyline; PARoxetine; Phenelzine; Protriptyline; Tranylcypromine; Trimipramine. Monitor therapy

Sibutramine: May enhance the adverse/toxic effect of Centrally Acting Weight Loss Agents. Avoid combination

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. 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 adverse/toxic effect of Amphetamines. Tricyclic Antidepressants may potentiate the cardiovascular effects of Amphetamines. Amphetamines may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased cardiovascular effects when these agents are combined. Monitor therapy

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

Test Interactions

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

Adverse Reactions

Frequency not defined.

Cardiovascular: Hypertension, ischemia, palpitations, tachycardia

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

Dermatologic: Urticaria

Endocrine & metabolic: Change in libido

Gastrointestinal: Constipation, diarrhea, gastrointestinal distress, unpleasant taste, xerostomia

Genitourinary: Impotence

Neuromuscular & skeletal: Tremor

<1%, postmarketing, and/or case reports: Acquired valvular heart disease (regurgitant), primary pulmonary hypertension

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Heart failure: In a scientific statement from the American Heart Association, phentermine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).
• 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. Use with caution in patients with mild hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate.
• 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.
• Renal impairment: Use caution in patients with renal impairment; an increase in exposure is expected. Avoid use in patients with eGFR <15 mL/minute/1.73 m², including end-stage renal disease (ESRD) requiring dialysis (has not been studied).
• Seizure disorders: Avoid or use with caution in patients with history of seizures (Apovian 2015).
• Tourette syndrome: Use with caution in patients with Tourette 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: Some products may contain tartrazine Some products may contain tartrazine (FDC yellow #5), 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. Therapy should be used in conjunction with a comprehensive weight management program.
• 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.

Monitoring Parameters

Weight and waist circumference every month for the first 3 months, then at 3-month intervals (Apovian 2015); blood pressure

Pregnancy

Pregnancy Risk Factor

X

Pregnancy Considerations

Use of phentermine is contraindicated during pregnancy (lack of potential benefit and possible fetal harm). Limited information is available about the use of phentermine in pregnancy (Jones 2002; McElhatton 2006). An increased risk of adverse maternal and fetal outcomes is associated with obesity; however, medications for weight loss therapy are not recommended at conception or during pregnancy (ACOG 156 2015).

Patient Education

What is this drug used for?

• It is used to treat obesity.

Frequently reported side effects of this drug

• Anxiety
• Constipation
• Diarrhea
• Dry mouth
• Trouble sleeping
• Bad taste
• Decreased sex drive
• Sexual dysfunction
• Agitation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Behavioral changes
• Chest pain
• Fast heartbeat
• Abnormal heartbeat
• Mood changes
• Tremors
• Shortness of breath
• Swelling of arms or legs
• Vision changes
• Severe dizziness
• Passing out
• Severe headache
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.