Weight management, short-term (alternative agent):
Note: Avoid use due to side effects (eg, tachycardia, hypertension), potential for abuse, and availability of preferred weight-reducing drugs (ES [Apovian 2015]; Perreault 2022). Limit use to patients who cannot take preferred agents and who have a BMI ≥30 kg/m2 or patients with a BMI ≥27 kg/m2 and ≥1 weight-associated comorbidity (eg, dyslipidemia) and who do not have contraindications for use. Maximum duration: 12 weeks. Some patients may develop tolerance to appetite suppressive effects; phendimetrazine should be discontinued when this occurs.
Extended release: Oral: 105 mg once daily 30 to 60 minutes before morning meal.
Immediate release: Oral: 17.5 to 35 mg 2 or 3 times daily, 1 hour before meals (maximum: 70 mg 3 times daily).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution (renally eliminated).
There are no dosage adjustments provided in the manufacturer's labeling.
Obesity (short-term): Oral: Adolescents ≥17 years: Extended-release: Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution (renally eliminated).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
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
Yes
C-III
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.
Oral: Extended-release capsule: Administer 30 to 60 minutes before morning meal.
Weight management, short-term: Short-term (eg, ≤12 weeks) 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, diabetes, hyperlipidemia) who have not responded to lifestyle modifications alone.
Bontril PDM may be confused with Bentyl
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
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)
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.
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.
Special populations:
• Older adult: 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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Risk X: Avoid combination
Alcohol (Ethyl): May enhance the adverse/toxic effect of Phendimetrazine. Risk C: 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. Risk D: Consider therapy modification
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: 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. Risk C: Monitor therapy
Antacids: May decrease the excretion of Amphetamines. Risk C: Monitor therapy
Antihypertensive Agents: Amphetamines may diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents: May enhance the adverse/toxic effect of Amphetamines. Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Antipsychotic Agents: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Amphetamines. Risk C: 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. Risk D: 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 Risk C: 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. Risk C: Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
Esketamine: May enhance the hypertensive effect of CNS Stimulants. Risk C: Monitor therapy
Gastrointestinal Acidifying Agents: May decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: 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. Risk X: 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. Risk X: Avoid combination
Ioflupane I 123: Amphetamines may diminish the diagnostic effect of Ioflupane I 123. Risk C: 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 antiseizure drugs. Risk D: 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 antiseizure drugs. Risk D: 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 antiseizure drugs. Risk D: Consider therapy modification
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Methenamine: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Risk C: 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. Risk X: 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. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Amphetamines. Specifically, vitamin C may impair absorption of amphetamines. Risk C: Monitor therapy
Opioid Agonists: Amphetamines may enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapy
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Quinolones: Amphetamines may enhance the cardiotoxic effect of Quinolones. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Sibutramine: May enhance the adverse/toxic effect of Centrally Acting Weight Loss Agents. Risk X: Avoid combination
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. CNS Stimulants may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: 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. Risk C: Monitor therapy
Urinary Acidifying Agents: May decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Obesity increases the risk of infertility. Optimal weight control prior to conception improves pregnancy outcomes. However, medications for weight loss are not recommended prior to pregnancy due to safety issues and adverse events. Weight loss medications should be discontinued prior to conception (ACOG 2021; Wharton 2020).
An increased risk of adverse maternal and fetal events is associated with obesity. However, moderate gestational weight gain based on prepregnancy BMI is required for positive fetal outcomes in all pregnancies, including patients with overweight or obesity. Therefore, medications for weight loss therapy are not recommended during pregnancy (ACOG 2021; Wharton 2020).
Use is contraindicated by some manufacturers in pregnant patients (lack of potential benefit and possible fetal harm).
It is unknown if phendimetrazine is present in breast milk; however, other amphetamines have been detected in breast milk.
Use is contraindicated by some manufacturers in breastfeeding patients. Due to safety concerns, medications for weight loss therapy are not recommended for patients who are breastfeeding (Wharton 2020).
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.
Baseline cardiac evaluation (for preexisting valvular heart disease, pulmonary hypertension); weight; waist circumference; BP; heart rate.
Adult classification of weight by BMI (kg/m2) (NHLBI 1998):
Underweight: <18.5
Normal: 18.5 to 24.9
Overweight: 25 to 29.9
Obesity, class I: 30 to 34.9
Obesity, class II: 35 to 39.9
Obesity, class III: ≥40
Waist circumference: In adults with a BMI of 25 to 34.9 kg/m2, high-risk waist circumference is defined as (NHLBI 1998):
Males >102 cm (>40 in)
Females >88 cm (>35 in)
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).
Half-life elimination: ~3.7 hours
Excretion: Urine
Capsule ER 24 Hour Therapy Pack (Phendimetrazine Tartrate ER Oral)
105 mg (per each): $3.12
Tablets (Phendimetrazine Tartrate Oral)
35 mg (per each): $0.19 - $0.33
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