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 (ES [Apovian 2015]). Evaluate weight loss after 4 weeks; continue therapy only if satisfactory weight loss (eg, 4 pounds, or as clinically appropriate) has occurred. Maximum duration: 12 weeks.
Immediate release: Oral: 25 mg 3 times daily 1 hour before meals; a fourth dose may be taken in the evening as needed for hunger.
Controlled release: Oral: 75 mg once daily in the midmorning.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling.
Adolescents >16 years: Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
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.
Tablet, Oral, as hydrochloride:
Generic: 25 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Generic: 75 mg
Yes
C-IV
Immediate release: Administer 1 hour before meals; may also administer 1 tablet midevening (to overcome night hunger).
Controlled release: Swallow whole; administer at midmorning.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to IR tablet.
Oral:
Immediate-release tablet: Administer 1 hour before meals; may also administer 1 tablet midevening (to overcome night hunger).
Controlled-release tablet: Swallow whole; administer at midmorning.
Weight management, short-term: Short-term (few weeks) in the management of exogenous obesity. Therapy should be used in conjunction with a comprehensive weight management program.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Cardiac arrhythmia, cerebrovascular accident, ECG changes, heart valve disease, hypertension, palpitations, tachycardia
Central nervous system: Anxiety, depression, dizziness, drowsiness, dysphoria, euphoria, headache, insomnia, jitteriness, malaise, nervousness, overstimulation, precordial pain, psychosis, restlessness, seizure
Dermatologic: Alopecia, diaphoresis, ecchymoses, erythema, skin rash, urticaria
Endocrine & metabolic: Changes in libido, gynecomastia, menstrual disease
Gastrointestinal: Abdominal distress, constipation, diarrhea, dysgeusia, nausea, vomiting, xerostomia
Genitourinary: Dysuria, impotence
Hematologic & oncologic: Agranulocytosis, bone marrow depression, leukopenia
Neuromuscular & skeletal: Dyskinesia, myalgia, tremor
Ophthalmic: Blurred vision, mydriasis
Renal: Polyuria
Respiratory: Dyspnea, pulmonary hypertension
Miscellaneous: Tachyphylaxis
Hypersensitivity or idiosyncrasy to diethylpropion or other sympathomimetic amines; advanced arteriosclerosis, severe hypertension; pulmonary hypertension; hyperthyroidism; glaucoma; agitated states, history of drug abuse; during or within 14 days following MAO inhibitor therapy, concurrent use with other anorectic agents
Concerns related to adverse effects:
• CNS effects: Amphetamines may impair the ability to engage in potentially hazardous activities (eg, driving or operating machinery).
• Heart failure: In a scientific statement from the American Heart Association, diethylpropion 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 found to occur with increased frequency in patients receiving some anorexigens, including diethylpropion; use of anorexigens for >3 months has been associated with a 23-fold increase in risk of pulmonary hypertension. If the patient develops signs or symptoms of pulmonary hypertension (eg, exertional dyspnea, angina, syncope, lower extremity edema), discontinue use immediately and evaluate.
• Valvular heart disease: The use of some anorexigens, including diethylpropion, has been associated with the development of valvular heart disease. The risk may be increased with extended use, higher than recommended doses, or concomitant use with other anorexigens. 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.
Disease-related concerns:
• Diabetes: Use with caution in patients with diabetes mellitus; antidiabetic agent requirements may be altered with anorexigens 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; avoid use in patients with severe hypertension.
• Psychiatric disorders: Use with caution in patients with preexisting psychosis or bipolar disorder (may induce mixed/manic episode). May exacerbate symptoms of behavior and thought disorder in psychotic patients; new-onset psychosis or mania may occur with stimulant use; observe for symptoms of aggression and/or hostility.
• Seizure disorders: Avoid or use with caution in patients with history of seizure disorders (Apovian, 2015).
• Tourette's syndrome: Use with caution in patients with Tourette's syndrome; stimulants may unmask tics.
Concurrent drug therapy issues:
• Anorexigens: Safety and efficacy have not been established for use with other weight loss medications, including over-the-counter or herbal products. Not recommended for use in patients who have used other anorectic agents within the past year.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
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: Diethylpropion 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.
• Discontinuation of therapy: Abrupt discontinuation following high doses or for prolonged periods may result in symptoms for withdrawal. Discontinue if satisfactory weight loss has not occurred within the first 4 weeks of treatment, or if tolerance develops.
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 Diethylpropion. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. 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
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
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
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
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
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
Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Diethylpropion. Risk X: Avoid combination
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. 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
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).
Diethylpropion crosses the human placenta; spontaneous reports of congenital malformations have been reported, but an association with diethylpropion has not been established. Withdrawal symptoms may occur in the neonate following maternal use of diethylpropion.
An increased risk of adverse maternal and fetal events is associated with obesity. However, moderate gestational weight gain based on pre-pregnancy 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).
Diethylpropion is present in breast milk.
The manufacturer recommends that caution be exercised when administering diethylpropion to 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. Take immediate release tablet 1 hour before meals or food.
Baseline cardiac evaluation (for preexisting valvular heart disease, pulmonary hypertension); echocardiogram during therapy; weight, waist circumference, blood pressure; renal function in elderly patients
Adult classification of weight by BMI (kg/m2):
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:
Males >102 cm (>40 in).
Females >88 cm (>35 in).
Diethylpropion is a sympathomimetic amine with pharmacologic properties similar to the amphetamines. It is also structurally similar to bupropion. The mechanism of action in reducing appetite appears to be secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine
Metabolism: Forms active metabolites via N-dealkylation and reduction
Half-life elimination: Aminoketone metabolites: ∼4-6 hours
Excretion: Urine
Tablet, 24-hour (Diethylpropion HCl ER Oral)
75 mg (per each): $1.95
Tablets (Diethylpropion HCl Oral)
25 mg (per each): $0.52 - $1.04
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