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Phendimetrazine

Medically reviewed by Drugs.com. Last updated on Aug 10, 2020.

Pronunciation

(fen dye ME tra zeen)

Index Terms

  • Bontril PDM
  • Phendimetrazine Tartrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as tartrate:

Generic: 105 mg

Tablet, Oral, as tartrate:

Generic: 35 mg

Pharmacologic Category

  • Anorexiant
  • Sympathomimetic

Pharmacology

Phendimetrazine 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.

Metabolism

Forms 2 metabolites (phenmetrazine and phendimetrazine-N-oxide).

Excretion

Urine

Half-Life Elimination

~3.7 hours

Use: Labeled Indications

Obesity (short-term adjunct): Short-term (eg, ≤12 weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification, and caloric restriction in the management of exogenous obesity in patients with an initial BMI ≥30 kg/m2 or a BMI ≥27 kg/m2 with at least one weight-related comorbidity (eg, controlled hypertension, diabetes, hyperlipidemia) who have not responded to lifestyle modifications alone.

Contraindications

Hypersensitivity or idiosyncrasy to phendimetrazine, other sympathomimetic amines, or any component of the formulation; glaucoma; pregnancy (AACE/ACE [Garvey 2016]); highly nervous or agitated patients; history of drug abuse; hyperthyroidism; coadministration with other anorectic agents or CNS stimulants; during or within 14 days following monoamine oxidase inhibitors therapy.

Additional contraindications:

Extended release: History of cardiovascular disease (eg, arrhythmias, heart failure, coronary artery disease, uncontrolled hypertension, pulmonary hypertension, stroke); breastfeeding.

Immediate release: Advanced arteriosclerosis; symptomatic cardiovascular disease; moderate and severe hypertension.

Dosing: Adult

Obesity (short-term adjunct): Oral:

Extended release: 105 mg once daily 30 to 60 minutes before morning meal.

Immediate release: 35 mg 2 or 3 times daily, 1 hour before meals. In some cases, one-half tablet (17.5 mg) per dose may be adequate (maximum: 70 mg 3 times daily).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Obesity (short-term): Oral: Adolescents ≥17 years: Extended-release: Refer to adult dosing.

Administration

Extended release: Administer 30 to 60 minutes before morning meal.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER capsule should be swallowed whole. Do not chew, crush, or divide. IR tablets are available. Bariatric surgery-induced GI transit alterations may theoretically increase or decrease medication absorption. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, careful evaluation of GI status (gastric emptying and small bowel transit), nutritional intake, and behavioral habits is strongly advised before administering anorexiant agents after bariatric surgery.

Immediate release: Administer 1 hour before meals.

Dietary Considerations

Most effective when combined with a low calorie diet and behavior modification counseling. Extended-release product should be taken 30 to 60 minutes before morning meal; immediate-release product should be taken 1 hour before meals.

Storage

Store at 15°C to 30°C (59°F to 86°F); protect capsules from moisture.

Drug Interactions

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

Alcohol (Ethyl): May enhance the adverse/toxic effect of Phendimetrazine. 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. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a strong CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs. 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

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

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

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

Procarbazine: May enhance the adverse/toxic effect of Sympathomimetics. Management: Consider alternatives to this combination when possible. Procarbazine prescribing information states that this combination should be avoided. Consider therapy modification

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 amphetamine toxicities, including serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust dose as needed. 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). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. 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. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. CNS Stimulants may enhance the tachycardic 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

Adverse Reactions

Frequency not defined.

Cardiovascular: Flushing, hypertension, ischemic events, palpitations, tachycardia, valvular disease (regurgitant)

Central nervous system: Agitation, dizziness, headache, insomnia, overstimulation, psychosis, restlessness

Endocrine & metabolic: Changes in libido

Gastrointestinal: Constipation, diarrhea, nausea, stomach pain, xerostomia

Genitourinary: Dysuria, urinary frequency

Neuromuscular & skeletal: Tremor

Ocular: Blurred vision, mydriasis

Respiratory: Primary pulmonary hypertension

Miscellaneous: Diaphoresis, tachyphylaxis

<1%, postmarketing, and/or case reports: Dilated cardiomyopathy, retinal vein occlusion (Cho 2016)

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: 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, phendimetrazine has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]).

• Pulmonary hypertension: May occur (rarely) and may be fatal. Use of an anorectic agent for >3 months increases the risk of pulmonary hypertension. If onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema occur, immediately discontinue and evaluate for the possible presence of pulmonary hypertension.

• Valvular heart disease: The use of some anorectic agents has been associated with the development of valvular heart disease; contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. Not recommended in patients with known heart murmur or valvular heart disease.

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus; antidiabetic agent requirements may be altered with anorexic agents and concomitant dietary restrictions.

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

• Renal impairment: Use with caution in patients with renal impairment.

• Seizure disorders: Use with caution in patients with a history of seizure disorders.

• 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.

Other warnings/precautions:

• Abuse potential: Phendimetrazine 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: Phendimetrazine is not approved for long-term use. Clinicians should carefully examine the potential benefits against potential risks associated with use of medications in this class. Therapy should be used in conjunction with a comprehensive weight management program. Phendimetrazine is not recommended for patients who used any anorectic agents within the prior year.

• Discontinuation of therapy: Abrupt discontinuation following prolonged high doses may be associated with extreme fatigue and depression.

• Tolerance: Tolerance to the anorectic effect of phendimetrazine develops within a few weeks; discontinue use if tolerance develops; do not exceed recommended dosage in an attempt to overcome tolerance.

Monitoring Parameters

Baseline cardiac evaluation (for preexisting valvular heart disease, pulmonary hypertension); weight; waist circumference; BP; heart rate.

Reproductive Considerations

Medications for weight loss therapy are not recommended at conception (ACOG 156 2015).

Pregnancy Risk Factor

X/C (product dependent)

Pregnancy Considerations

Animal reproduction studies have not been conducted. Use is contraindicated by some manufacturers in pregnant women (lack of potential benefit and possible fetal harm). An increased risk of adverse maternal and fetal outcomes is associated with obesity; however, medications for weight loss therapy are not recommended during pregnancy (ACOG 156 2015).

Patient Education

What is this drug used for?

• It is used to treat obesity.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Anxiety

• Dry mouth

• Trouble sleeping

• Constipation

• Diarrhea

• Flushing

• Nausea

• Abdominal pain

• Agitation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Mood changes

• Chest pain

• Fast heartbeat

• Severe dizziness

• Passing out

• Vision changes

• Severe headache

• Shortness of breath

• Swelling of arms or legs

• Blurred vision

• Sex drive changes

• Abnormal heartbeat

• Passing a lot of urine

• Fatigue

• Loss of strength and energy

• Trouble breathing

• Trouble urinating

• Tremors

• Sweating a lot

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.