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Appetite Suppressants, Sympathomimetic (Systemic)

This monograph includes information on the following:

1) Benzphetamine  
2) Diethylpropion
3) Mazindol
4) Phendimetrazine  
5) Phentermine


INN:
Benzphetamine  —Benzfetamine
Diethylpropion—Amfepramone

VA CLASSIFICATION
Benzphetamine
Primary: GA751

Diethylpropion
Primary: GA751

Mazindol
Primary: GA751

Phendimetrazine
Primary: GA751

Phentermine
Primary: GA751


Note: Controlled substance classification—

Note: Controlled substances in the U.S. and Canada as follows:



Drug
U.S.
Canada
Benzphetamine
III {16}
Not available
Diethylpropion
IV {08}
C {25}
Mazindol
IV {39}
 
Phendimetrazine
III {02}
Not available
Phentermine
IV {01}
C {27}
Commonly used brand name(s): Adipex-P5; Adipost4; Bontril PDM4; Bontril Slow-Release4; Didrex1; Fastin5; Ionamin5; Mazanor3; Melfiat4; Obenix5; Obezine4; PT 1054; Phendiet4; Phendiet-1054; Phentercot5; Phentride5; Plegine4; Prelu-24; Pro-Fast5; Sanorex3; Tenuate2; Tenuate Dospan2; Tepanil Ten-Tab2; Teramine5; Zantryl5.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Appetite suppressant—

Indications

General considerations
Short-term clinical trials have shown that subjects treated with an appetite suppressant and dietary management instruction lose more weight than subjects treated with a placebo and dietary management instruction {01} {39}. However, the additional weight loss averages less than 0.5 kg (1 pound) per week, and tolerance to the effects of medications in this class usually develops within a few weeks {01} {16}. Rebound weight gain may occur after the medication is discontinued {04} {25}. Also, abuse of and dependence on the appetite suppressant may develop {39}. The limited usefulness of these agents should be measured against risk factors inherent in their use {01} {16}.

Accepted

Obesity, exogenous (treatment)—Benzphetamine {16}, diethylpropion {08} {25}, mazindol {04}, phendimetrazine {15}, and phentermine {01} {27} are indicated in the short-term (a few weeks) treatment of exogenous obesity in conjunction with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of ³ 30 kg of body weight per height in meters squared (kg/m 2) or in patients with a body mass index of ³ 27 kg/m 2 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia {01} {60}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Benzphetamine {16}, diethylpropion {08}, phendimetrazine {15}, and phentermine {09} are phenylalkylamines, related to amphetamine both chemically and pharmacologically.
    Mazindol is an isoindole with pharmacological effects similar to those of amphetamine {39}.
Molecular weight—
    Benzphetamine hydrochloride: 275.82 {05}
    Diethylpropion hydrochloride: 241.76 {05}
    Mazindol: 284.75 {05}
    Phendimetrazine tartrate: 341.36 {05}
    Phentermine: 149.24 {05}
    Phentermine hydrochloride: 185.70 {05}

Mechanism of action/Effect:

Although the mechanism of action of the sympathomimetic appetite suppressants in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Amphetamine and related sympathomimetic medications, except for mazindol, are thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite {20} {41}. Mazindol is thought to inhibit the reuptake of norepinephrine rather than to cause its release {48}. It has not been established that the action of these medications in treating obesity is primarily suppression of appetite {01} {08} {41}; other central nervous system (CNS) actions and/or metabolic effects, such as decreased gastric acid secretion or increased energy expenditure, may be involved {01} {08} {41}. Tolerance to the pharmacological effects of drugs of this class has been shown to develop {01} {08}.


Other actions/effects:

The sympathomimetic appetite suppressants produce CNS stimulation and elevation of blood pressure {01} {08} {39}. The CNS-stimulating effect of mazindol may be less than that of other sympathomimetics {20}.

Biotransformation:

Hepatic {18}.

Benzphetamine's metabolites include amphetamine and methamphetamine, which may cause positive results in urine screens for amphetamines {46}.

Diethylpropion undergoes complex metabolism, involving N-dealkylation and reduction, to several active metabolites {47}.

Phentermine is not significantly biotransformed {53}; 70 to 80% of a given dose is excreted in the urine unchanged {53}.

Elimination:
    Primarily renal {21} {47} {48}; excretion is increased by acidifying the urine {16} {21} {46}.




Drug
Half-life (hr)
Duration of action (hr)
Benzphetamine
6–12 {37}
 
Diethylpropion
4–6 {36}
 
-Tablets
  6–8 {61}
-Extended-release Tablets
  12
Mazindol
10 {04}–13 {57}
8–15
Phendimetrazine
*
 
 
Phentermine
19–24 {38} {57}
 
-Capsules (30 mg), Tablets
   
(37.5 mg), or Resin Capsules
  12–14 {01} {26}
* Plasma concentrations of phendimetrazine decline by 50% in approximately 1.9 hours with the tablet dosage form and in approximately 9.8 hours with the extended-release capsule dosage form {21}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other sympathomimetics (for example, amphetamines, ephedrine, epinephrine, isoproterenol, metaproterenol, norepinephrine, phenylephrine, phenylpropanolamine, pseudoephedrine, terbutaline) may be sensitive to this medication also {09}.

Carcinogenicity/Mutagenicity

Studies have not been done {01} {08}.

Pregnancy/Reproduction

Pregnancy—

All sympathomimetic appetite suppressants

Abuse of these medications during pregnancy may result in withdrawal symptoms in the neonate {08}.

Infants of mothers who abused amphetamines (to which sympathomimetic appetite suppressants are pharmacologically similar) during pregnancy have shown clefting, cardiac anomalies, and fetal growth retardation {62}. All of these effects have been demonstrated in animal studies of prenatal amphetamine exposure also {62}. Additional adverse effects seen in infants exposed in utero to amphetamines, such as altered behavior, may be related to environmental factors and/or direct medication effects {16}.



Benzphetamine

Benzphetamine is contraindicated during pregnancy because it may cause harm to the fetus {16}.

FDA Pregnancy Category X {16}.



Diethylpropion

Adequate and well-controlled studies in humans have not been done. Studies in rats at doses of up to nine times the human dose have revealed no effect on fertility and no teratogenic effects {08}.

FDA Pregnancy Category B {08}.



Mazindol

Adequate and well-controlled studies in humans have not been done. Studies in rats and rabbits at high doses have shown increases in neonatal mortality and possibly in the incidence of rib anomalies in the rats {39}.

FDA pregnancy category not currently included in product labeling.



Phendimetrazine

Safety in pregnancy has not been established {02}.

FDA pregnancy category not currently included in product labeling.



Phentermine

Studies have not been done in humans or in animals {01}.

FDA Pregnancy Category C {01}.


Breast-feeding

Diethylpropion {08} and/or its metabolites {08}, and benzphetamine {16} are distributed into breast milk. It is not known if the other appetite suppressants are distributed into breast milk {40}. However, because of the potential for serious adverse effects on the nursing infant, breast-feeding while taking an appetite suppressant is not recommended {01} {40}.

Pediatrics

Appetite suppressants are not recommended for use in children up to 16 years of age {60}, because appropriate studies have not been performed in the pediatric population {08}.


Geriatrics


No information is available on the relationship of age to the effects of the appetite suppressants in geriatric patients.


Dental

Appetite suppressants may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

Agranulocytosis or leukopenia, reported rarely with use of diethylpropion {08}, may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. If agranulocytosis or leukopenia occurs, dental work should be deferred until blood counts have returned to normal. Patient instruction in proper oral hygiene should include caution in use of regular toothbrushes, dental floss, and toothpicks.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Acidifiers, urinary, such as:
Ammonium chloride or
Ascorbic acid or
Potassium or sodium phosphates    (excretion of appetite suppressant may be increased, leading to decreased serum concentrations {09} {16} {40})


Alcohol    (concurrent use with appetite suppressants is not recommended {01} {08} since this may increase the potential for CNS effects such as dizziness, lightheadedness, fainting, or confusion)


Alkalizers, urinary, such as:
Antacids, calcium- and/or magnesium-containing or
Carbonic anhydrase inhibitors or
Citrates or
Sodium bicarbonate    (excretion of appetite suppressant may be decreased, leading to increased serum concentrations {16})


Anesthetics, hydrocarbon inhalation, especially:
» Halothane    (halothane, and possibly other inhalation anesthetics, sensitizes the myocardium to the effects of sympathomimetics {13} {14}; cardiac arrhythmias may occur {04} {13} {14}; also, it is theoretically possible for intracellular stores of catecholamines to be depleted by sympathomimetic appetite suppressant use, causing resuscitation efforts to be unsuccessful {59})


» Antidepressants, tricyclic    (cardiovascular response to increased norepinephrine plasma concentrations may be exaggerated, leading to hypertension and/or cardiac arrhythmias {27} {51})


Antidiabetic agents, oral or
Insulin    (when appetite suppressants and the concurrent dietary regimen are used in the treatment of obesity, blood glucose concentrations may be altered in patients with diabetes mellitus {01} {08}; dosage adjustment of the hypoglycemic agent may be necessary during and after concurrent therapy {01} {08} {39})


Antihypertensives, especially clonidine, guanadrel, guanethidine, methyldopa, or rauwolfia alkaloids    (hypotensive effects may be decreased {01} {02} {04})


» Appetite suppressants, other, including amphetamines or
» Selective serotonin reuptake inhibitors (SSRIs)    (an increased prevalence of abnormal cardiac valve function, primarily aortic regurgitation, was found on echocardiographic evaluation in patients receiving phentermine in combination with either dexfenfluramine or fenfluramine, both of which act to suppress appetite by increasing serotonergic function {63} {64} {50}; however, an increased prevalence of abnormal cardiac valve function also has been found in patients receiving dexfenfluramine or fenfluramine alone {54} {64} {65}, and the role of phentermine in producing the cardiotoxic effect is uncertain {28}; because of the severity of these cardiovascular effects and because the safety and efficacy of other appetite suppressant combinations have not been established, combined use is not recommended {01}; also, the safety and efficacy of combining an SSRI, which enhances serotonergic function, with a sympathomimetic appetite suppressant have not been established and combined use is not recommended {01})

    (restlessness, racing thoughts, stomach cramps, tremor, palpitation, and hyperreflexia were reported in a woman who took 30 mg of phentermine 8 days after discontinuing fluoxetine {11})


» CNS stimulation–producing medications, other (see Appendix II ) or
Thyroid hormones    (concurrent use may increase the CNS-stimulant effects of either these medications or the appetite suppressant {02} {04})


» Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline    (the sympathomimetic effects of appetite suppressants may be potentiated, possibly resulting in a hypertensive crisis; concurrent use is contraindicated; appetite suppressants should not be administered during or within 14 days following the administration of an MAO inhibitor {01} {02} {39})


Phenothiazines    (anorectic effects of the appetite suppressant may be antagonized {08})


» Vasopressors, especially catecholamines    (vasopressant effect may be potentiated {04} {08}; if necessary to administer a pressor amine agent to a patient who has recently received an appetite suppressant, initiating pressor therapy in reduced dosage and monitoring blood pressure at frequent intervals are recommended {04} {39})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Urine screen for amphetamines    (the use of a sympathomimetic appetite suppressant may produce a positive result {60})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Agitated states{08}{09}{39} or
» Arteriosclerosis, advanced{02}{08}{09} or
» Cardiovascular disease, symptomatic, including arrhythmias{02}{09}{39} or
» Cerebral ischemia{04} or
» Glaucoma{08}{09}{39} or
» Hypertension, moderate to severe{02}{09}{15} or
» Hyperthyroidism{02}{08}{09} or
» Psychosis, especially schizophrenia{04}{60}    (condition may be exacerbated)


» Alcoholism, active or in remission{60} or
» Drug abuse or dependence, or history of{08}{09}{39}    (dependence on appetite suppressants may be more likely to develop)


» Uremia{04}    (excretion of appetite suppressant may be altered)


Risk-benefit should be considered when the following medical problems exist
Affective illness, or family history of or
Psychosis, family history of    (mental depression {19} {44} or psychosis {42} {44} may be more likely to occur)


Diabetes mellitus    (use of appetite suppressants and concomitant dietary restrictions may change the amount of insulin or oral antidiabetic agents needed {01} {02} {39})


Epilepsy    (diethylpropion may increase the number of seizures in patients with epilepsy {08}; careful monitoring is recommended {08})


» Hypertension, mild{01}{02}{39}    (condition may be exacerbated)


» Sensitivity to appetite suppressants or other sympathomimetics{01}{04}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Cardiac evaluations    (recommended to detect cardiopulmonary disease in patients who are receiving appetite suppressants in combination or for long-term treatment {31}; heart murmur usually is detectable before more severe symptoms of valvular heart disease develop {31})




Side/Adverse Effects

Note: An epidemiologic study found an increased risk of primary pulmonary hypertension (PPH) in patients who had used anorexigenic medications within the previous year or for a duration of more than 3 months {33}. Most cases of PPH occurred in patients who had used the serotonin-releasing agents fenfluramine and dexfenfluramine, which are no longer available for clinical use {33}. There have been rare cases of PPH reported in patients who had used sympathomimetic appetite suppressants only {33} {55} {58}; however, the role of these medications in the development of PPH is unclear {33}. The risk in the general population of developing PPH is about one to two cases per million persons per year {33}, and the risk associated with obesity is about twofold higher {15} {25}. This condition has a 4-year survival rate of about 55% {32}.
Abnormalities in the mitral, aortic, and/or tricuspid valves that resemble those seen in carcinoid syndrome or ergotamine toxicity {31} have been reported in patients receiving the combination of phentermine and fenfluramine for 1 to 28 months {31}. Heart murmur was usually detectable before more severe symptoms developed {31}. There have been rare reports of valvular heart disease in patients receiving phentermine monotherapy {01} and in patients with a history of appetite suppressant use who were receiving phendimetrazine monotherapy when diagnosed {49}.
Although both PPH {33} and cardiac-valve disease {56} have been reported primarily with the use of fenfluramine, dexfenfluramine, or combinations that included one of these two medications, the possibility that these conditions may occur with the use of sympathomimetic appetite suppressants should be considered {60}. Appetite suppressant treatment should be discontinued in any patient who develops unexplained dyspnea, angina pectoris, syncope, or lower extremity edema {32}. These patients should be evaluated for pulmonary hypertension {32} and valvular heart disease {29}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Elevated blood pressure{01}{02}{08}

Incidence less frequent or rare
    
Agranulocytosis or leukopenia{08} (sore throat and fever; unusual bleeding or bruising)—with diethylpropion{08}
    
allergic reaction{01}{08} (skin rash or hives)
    
cardiomyopathy{45} or valvular heart disease{01}{15} (decreased ability to exercise; swelling of feet or lower legs; trouble in breathing)—may be asymptomatic
    
cerebral ischemia or stroke{43} (headache, severe; numbness, especially on one side of the face or body)
    
dysuria{02}{08}{40} (difficult or painful urination)
    
mania{44} (talking, feeling, and acting with excitement and activity you cannot control)
    
mental depression{08}{19}{24}
    
palpitation{01}{08}{39} (fast or irregular heartbeat)
    
primary pulmonary hypertension{01}{32}{33} (chest pain; decreased ability to exercise; fainting; swelling of feet or lower legs; trouble in breathing)
    
psychosis{08}{42}{44} (feeling that others can hear your thoughts; feeling that others are watching you or controlling your behavior; feeling, seeing, or hearing things that are not there)—may be more likely to occur in patients with a family history of affective illness{19} or psychosis{42}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
CNS stimulation{01}{08}{39} (false sense of well-being or mild euphoria; irritability; nervousness or restlessness; trembling or shaking; trouble in sleeping)—may be followed by drowsiness, fatigue, or mental depression{27}
    
constipation{08}{39}{41}
    
dizziness or lightheadedness{08}{40}{41}
    
dryness of mouth{08}{39}{41}
    
headache{01}{08}{40}
    
nausea or vomiting{08}{39}{41}
    
stomach cramps or pain{02}{41}

Incidence less frequent or rare
    
Blurred vision{02}{08}{40}
    
changes in libido{01}{08}{39} (changes in sexual desire)
    
diarrhea{01}{08}{39}
    
drowsiness{08}{39}
    
impotence{01}{08} (decreased sexual ability)
    
increased sweating{08}{39}
    
polyuria or urinary frequency{02}{08} (frequent urge to urinate or increased urination)
    
unpleasant taste{01}{08}{39}



Those indicating possible abuse and/or the need for medical attention
    
Dermatoses, severe{01}{08} (skin disease)
    
hyperactivity{01}
    
insomnia, severe{01}{08} (trouble in sleeping)
    
irritability, severe{01}{08}
    
personality changes{01}{08}
    
psychosis{01}{02}{08} —often indistinguishable from schizophrenia{01}{02}{08}


Those indicating possible withdrawal and/or the need for medical attention if they occur after medication is discontinued
    
Fatigue, severe{01}{02}{08} (extreme tiredness or weakness)
    
mental depression{01}{02}{08}
    
nausea or vomiting
    
stomach cramps or pain
    
trembling
    
trouble in sleeping or nightmares{18}




Overdose
For specific information on the agents used in the management of appetite suppressant overdose, see:
   • Barbiturates (Systemic) monograph;
   • Beta-adrenergic Blocking Agents (Systemic) monograph;
   • Charcoal, Activated (Oral-Local) monograph;
   • Diazepam in Benzodiazepines (Systemic) monograph;
   • Lidocaine (Systemic) monograph;
   • Neuromuscular Blocking Agents (Systemic) monograph;
   • Nitrates (Systemic) monograph;
   • Phentolamine (Systemic) monograph; and/or
   • Phenytoin in Anticonvulsants, Hydantoin (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Cardiovascular effects
including arrhythmias {01} {08}
irregular blood pressure {01} {08}
or circulatory collapse {01} {08} (dizziness, lightheadedness, or fainting; irregular heartbeat)
    
CNS effects
including confusion {01} {08} {16}
hallucinations {01} {08} ( seeing, hearing, or feeling things that are not there), hostility with assaultiveness {01} {08} {10}
panic state {01} {08}
or restlessness {01} {08} —CNS excitement is usually followed by fatigue and depression {01} {02} {08}
    
convulsions {24} and coma {02} {24} —seen in most cases of fatal overdose {01} {16}
    
fast breathing {08} {16}
    
gastrointestinal effects
including abdominal or stomach cramps {01} {08}
diarrhea {01} {08}
nausea {01} {08}
or vomiting {01} {08}
    
hyperreflexia {01} {08} (overactive reflexes)
    
hyperthermia {52} (fever)
    
tremor {01} {08} (trembling or shaking)


Treatment of overdose
There is no specific antidote for overdosage with appetite suppressants; treatment is symptomatic and supportive {01} {16} {52}.


To decrease absorption:
Induction of emesis {04} {40} and/or use of gastric lavage {01} {08} {40} followed by the administration of activated charcoal {04}.



To enhance elimination:
Acidification of urine {01} {40} and forced diuresis {40}, with serum electrolyte evaluations during prolonged diuresis {40}.



Specific treatment:
Barbiturate sedatives {01} {08} or diazepam {52} sometimes used to control excessive CNS stimulation.

Intravenous diazepam to control seizures {52}; phenytoin to control seizures that are refractory to diazepam {52}. When hyperthermia and rhabdomyolysis are present, curarization may be required {52}.

Intravenous phentolamine {01} {08} or nitrates {23}, if necessary, to control acute, severe hypertension.

Intravenous lidocaine for cardiac arrhythmias {04}.

Beta-adrenergic blocking agent for control of tachycardia {52}.



Monitoring:
Monitoring of cardiovascular and respiratory functions and body temperature {52}.



Supportive care:
Intravenous fluids for hypotension control {52}.

Mechanical respiration, when necessary.

Protection of patient from self-injury {52} by use of restraints if necessary.

Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Note: The efficacy of hemodialysis or peritoneal dialysis in the treatment of appetite suppressant overdose is uncertain {01} {08} {39}.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Appetite Suppressants, Sympathomimetic (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to appetite suppressants or other sympathomimetics

Pregnancy—Abuse of medication during pregnancy may lead to withdrawal symptoms in the neonate; abuse of amphetamines during pregnancy can lead to clefting defects, cardiac anomalies, and fetal growth deficits; benzphetamine is contraindicated (FDA Category X) in pregnancy





Breast-feeding—Benzphetamine and diethylpropion are distributed into breast milk; other appetite suppressants may be distributed into breast milk





Use in children—Not recommended for appetite suppression in children up to 16 years of age




Contraindicated medications
Monoamine oxidase (MAO) inhibitors
Other medications, especially other appetite suppressants, other CNS stimulants, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, or vasopressors
Other medical problems, especially agitated states, alcoholism, advanced arteriosclerosis, symptomatic cardiovascular disease including arrhythmias, cerebral ischemia, history of drug abuse or dependence, glaucoma, hypertension, hyperthyroidism, psychosis, or uremia

Proper use of this medication

Timing last dose of day to minimize insomnia
For dosage forms and strengths that allow once-a-day dosing, taking the dose about 10 to 14 hours before bedtime {07}

For dosage forms and strengths that require more than one dose per day to be taken, taking the last dose of the day at least 4 to 6 hours before bedtime
For extended-release dosage forms—Swallowing whole; not breaking, crushing, or chewing

For mazindol—Taking with food if stomach upset occurs

» Not taking more medication than the amount prescribed, because of increased incidence of side effects and habit-forming potential

» Proper dosing
Missed dose: Skipping missed dose and returning to regular dosing schedule; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress during therapy and to check for adverse effects

» Not increasing dose if medication is not effective after a few weeks; checking with physician

» Not taking appetite suppressant with or less than 14 days after taking an MAO inhibitor

Possible positive result in urine screen for amphetamines

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks

» Caution if dizziness, drowsiness, lightheadedness, or elated mood or euphoria occurs; not driving or using machines or doing other things that require alertness until effects of medication are known

» Caution if any kind of surgery, dental treatment, or emergency treatment is required, because of possible interaction with medications used in these situations

» Reporting chest pain, decreased exercise tolerance, fainting, swelling of feet or lower legs, or trouble in breathing to physician immediately

» Suspected physical or psychological dependence: Checking with physician

Diabetic patients: Insulin or oral antidiabetic–agent requirements may be altered; checking with physician

» Checking with physician before discontinuing medication after prolonged or high-dose therapy; gradual dosage reduction may be necessary to avoid withdrawal symptoms


Side/adverse effects
Symptoms of potential side effects, especially elevated blood pressure, agranulocytosis or leukopenia (with diethylpropion), allergic reaction, cardiomyopathy or valvular heart disease, cerebral ischemia or stroke, dysuria, mania, mental depression, palpitation, primary pulmonary hypertension or psychosis

Effects of abuse, including severe dermatoses, hyperactivity, severe insomnia, severe irritability, personality changes, or psychosis

Possibility of withdrawal symptoms


General Dosing Information
The dosing of appetite suppressants should be individualized to obtain an adequate response with the lowest effective dosage {15} {39}.

To reduce the possibility of insomnia caused by sympathomimetic appetite suppressants, the last dose of the regular dosage form for each day should be taken approximately 4 to 6 hours before bedtime and the daily dose of the extended-release or long-acting dosage form should be taken approximately 10 to 14 hours before bedtime {07}.

Sympathomimetic appetite suppressants are recommended for short-term use only {01} {39}. Tolerance to the anorectic effect may develop in a few weeks {01} {39}.

If tolerance to the anorectic effect develops, the medication should be discontinued {16}. The dosage should not be increased in an attempt to increase the effect {01} {39}.

Patients should report decreased exercise tolerance to physician immediately, as this may be an early symptom of primary pulmonary hypertension {32} or a symptom of valvular heart disease {31}. Also, any chest pain, fainting, swelling of feet or lower legs, or trouble in breathing should be reported to physician immediately, and appetite suppressant treatment should be discontinued {32}.

Prolonged use, especially of larger-than-usual therapeutic doses, may result in psychological or physical dependence {01} {39}.

When the medication is to be discontinued following prolonged or high-dose administration, the dosage should be reduced gradually in order to avoid the possibility of a rebound increase in appetite {12} and to minimize withdrawal symptoms {25}.

Diet/Nutrition
Appetite suppressants are meant to be used in conjunction with a reduced-calorie diet as well as an exercise program and behavior modification. Changes in eating and activity behaviors must be long-term in order to maintain weight loss {60}.

BENZPHETAMINE

Summary of Differences


Pharmacology/pharmacokinetics:
Biotransformation—Metabolites include amphetamine and methamphetamine.



Precautions:
Pregnancy/reproduction—FDA Pregnancy Category X.



Oral Dosage Forms

BENZPHETAMINE HYDROCHLORIDE TABLETS

Usual adult dose
Appetite suppressant
Oral, initially, 25 to 50 mg once per day in midmorning or midafternoon, depending on the patient's eating habits; the dosage may be increased, as needed and tolerated, to 25 to 50 mg one to three times per day {16}.


Usual adult prescribing limits
150 mg per day {37}.

Usual pediatric dose
Children up to 16 years of age—Use is not recommended {16}.

Strength(s) usually available
U.S.—


50 mg (Rx) [Didrex (scored) (lactose) (sorbitol){16}]

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a tight container, unless otherwise specified by manufacturer.

Note: Controlled substance in the U.S.



DIETHYLPROPION

Summary of Differences


Precautions:
Medical considerations/contraindications—Caution also needed in epilepsy.



Side/adverse effects:
Agranulocytosis or leukopenia has occurred rarely.



Oral Dosage Forms

DIETHYLPROPION HYDROCHLORIDE TABLETS USP

Usual adult dose
Appetite suppressant
Oral, 25 mg three times per day, one hour before meals {08} {25}. One dose may be taken in mid-evening, if desired, to overcome night hunger {08}.


Usual pediatric dose
Children up to 16 years of age—Use is not recommended {08} {25}.

Strength(s) usually available
U.S.—


25 mg (Rx) [Tenuate (lactose){08}][Generic]

Canada—


25 mg (Rx) [Tenuate (lactose){25}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Note: Controlled substance in both the U.S. and Canada.



DIETHYLPROPION HYDROCHLORIDE EXTENDED-RELEASE TABLETS

Usual adult dose
Appetite suppressant
Oral, 75 mg once per day at mid-morning {08} {25}.


Usual pediatric dose
Children up to 16 years of age—Use is not recommended {08} {25}.

Strength(s) usually available
U.S.—


75 mg (Rx) [Tenuate Dospan{08}] [Tepanil Ten-Tab][Generic]

Canada—


75 mg (Rx) [Tenuate Dospan{25}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Swallow tablets whole.

Note: Controlled substance in both the U.S. and Canada.



MAZINDOL

Summary of Differences


Pharmacology/pharmacokinetics:
Chemical group—Isoindole.

Mechanism of action/effect—Inhibits reuptake of norepinephrine rather than causing its release.

Other actions/effects—May have less CNS-stimulating effect than other sympathomimetics.



Oral Dosage Forms

MAZINDOL TABLETS USP

Usual adult dose
Appetite suppressant
Oral, initially, 1 mg once per day, the dosage being increased as needed and tolerated {39} {40}; usual dosage is 1 mg three times per day one hour before meals {04}, or 2 mg once per day one hour before lunch {39}.

Note: Doses may be taken with meals to prevent stomach upset {04} {39}.



Usual adult prescribing limits
3 mg per day {40}.

Usual pediatric dose
Children up to 16 years of age—Use is not recommended {04} {39}.

Strength(s) usually available
U.S.—


1 mg (Rx) [Mazanor (scored) (lactose){39}] [Sanorex (lactose){40}]


2 mg (Rx) [Sanorex (scored) (lactose){40}]

Canada—


1 mg (Rx) [Sanorex (corn starch) (lactose) (tartrazine){04}]


2 mg (Rx) [Sanorex (scored) (corn starch) (lactose) (tartrazine){04}]

Packaging and storage:
Store below 25 °C (77 °F), unless otherwise specified by manufacturer. Store in a tight container.

Note: Controlled substance in the U.S.



PHENDIMETRAZINE


Oral Dosage Forms

PHENDIMETRAZINE TARTRATE EXTENDED-RELEASE CAPSULES

Usual adult dose
Appetite suppressant
Oral, 105 mg once per day, thirty to sixty minutes before the morning meal {21}.


Usual pediatric dose
Children up to 16 years of age—Use is not recommended {21}.

Strength(s) usually available
U.S.—


105 mg (Rx) [Adipost{22}] [Bontril Slow-Release{21}] [Melfiat{22}] [Phendiet-105{22}] [Prelu-2{22}] [PT 105{22}][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Swallow capsules whole.

Note: Controlled substance in the U.S.



PHENDIMETRAZINE TARTRATE TABLETS USP

Usual adult dose
Appetite suppressant
Oral, 17.5 to 35 mg two or three times per day one hour before meals {02} {15} {23}.


Usual adult prescribing limits
70 mg three times per day (210 mg per day) {02} {15} {23}.

Usual pediatric dose
Children up to 16 years of age—Use is not recommended {23}.

Strength(s) usually available
U.S.—


35 mg (Rx) [Bontril PDM (scored){23}] [Obezine{22}] [Phendiet{22}] [Plegine (scored) (lactose){15}][Generic] (may be single- or double-scored{02})

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Note: Controlled substance in the U.S.



PHENTERMINE


Oral Dosage Forms

PHENTERMINE HYDROCHLORIDE CAPSULES USP

Usual adult dose
Appetite suppressant
Oral, 15 to 37.5 mg once per day before breakfast {24} or one to two hours after breakfast {01} {24} {26}.


Usual pediatric dose
Children up to 16 years of age—Use is not recommended {26}.

Strength(s) usually available
U.S.—


15 mg (Rx)[Generic]


18.75 mg (Rx) [Phentercot{22}] [Pro-Fast (parabens){55}][Generic]


30 mg (Rx) [Fastin (sucrose){01}] [Phentercot{22}] [Phentride{22}] [Teramine{22}] [Zantryl{22}][Generic]


37.5 mg (Rx) [Adipex-P{24}] [Obenix{22}] [Phentercot{22}] [Pro-Fast (FD&C Yellow #5 [tartrazine]) (parabens){55}][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Note: Controlled substance in both the U.S. and Canada.



PHENTERMINE HYDROCHLORIDE TABLETS USP

Usual adult dose
Appetite suppressant
Oral, 15 to 37.5 mg per day, as a single dose before breakfast or one to two hours after breakfast {24}, or in two {24} or three divided doses one half hour before meals {09}.


Usual pediatric dose
Children up to 16 years of age—Use is not recommended {26}.

Strength(s) usually available
U.S.—


8 mg (Rx) [Phentercot{22}] [Teramine{22}][Generic] (may be scored){09}


37.5 mg (Rx) [Adipex-P (scored){24}] [Phentercot{22}][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Note: Controlled substance in the U.S.



PHENTERMINE RESIN CAPSULES

Usual adult dose
Appetite suppressant
Oral, 15 or 30 mg once per day before breakfast {07} {27}.


Usual pediatric dose
Children up to 16 years of age—Use is not recommended {27}.

Strength(s) usually available
U.S.—


15 mg (Rx) [Ionamin (lactose){07}]


30 mg (Rx) [Ionamin (lactose){07}]

Canada—


15 mg (Rx) [Ionamin (lactose){27}]


30 mg (Rx) [Ionamin (lactose){27}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a tight container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Swallow capsules whole.
   • Take in the morning.

Note: Controlled substance in both the U.S. and Canada.




Revised: 04/26/1999



References
  1. Phentermine hydrochloride capsules package insert (Fastin, SmithKline Beecham—US), Rev 3/98, Rec 7/98.
  1. Phendimetrazine tartrate tablets package insert (Camall—US), Rev 8/94, Rec 9/98.
  1. Manufacturer comment, 1987.
  1. Mazindol product monograph (Sanorex, Novartis—Canada). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1507-8.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 90, 234, 440, 566, 569.
  1. Panel comment.
  1. Phentermine resin package insert (Ionamin Capsules, Medeva—US), Rev 2/97, Rec 9/98.
  1. Diethylpropion hydrochloride package insert (Tenuate and Tenuate Dospan, Merrell Pharmaceuticals—US), Rev 2/96, Rec 9/98.
  1. Phentermine hydrochloride package insert (Camall—US), Rev 11/97, Rec 9/98.
  1. Manufacturer comment, 5/89.
  1. Bostwick JM, Brown TM. A toxic reaction from combining fluoxetine and phentermine [letter]. J Clin Psychopharmacol 1996; 16(2): 189-90.
  1. Reviewer comment, 4/89.
  1. Halothane package insert (Fluothane, Ayerst Laboratories—US), Rev 1/91, Rec 6/91.
  1. Bennett JA, Eltringham RJ. Possible dangers of anaesthesia in patients receiving fenfluramine. Anaesthesia 1977; 32: 8-13.
  1. Phendimetrazine tartrate tablets package insert (Plegine, Wyeth-Ayerst—US), Rev 1/98, Rec 9/98.
  1. Benzphetamine package insert (Didrex, Upjohn—US), Rev 1/98, Rec 12/98.
  1. Bray GA. Current status of drug therapy in obesity. In: Morgan JP, Kagan DV, Brody JS, editors. Phenylpropanolamine: risks, benefits, and controversies. New York: Praeger Publishers; 1985. p. 104-5.
  1. Diethylpropion package insert (Tepanil, Riker—US), Rev 9/85, Rec 6/87.
  1. Rihmer Z, Révai K, Arató M, et al. Two case reports of mazindol-induced depression [letter]. Am J Psychiatry 1984; 141(11): 1497-8.
  1. Gilman AG, Hardman JG, Limbird LE, et al, editors. Goodman & Gilman's: the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1996. p. 219-24.
  1. Phendimetrazine tartrate slow-release capsules package insert (Bontril, Carnrick—US), Rev 2/98, Rec 9/98.
  1. Cardinale V, editor. 1998 Drug topics red book. Montvale, NJ: Medical Economics Company; 1998.
  1. Phendimetrazine tartrate tablets package insert (Bontril PDM, Carnrick—US), Rev 7/97, Rec 9/98.
  1. Phentermine hydrochloride package insert (Adipex-P, Gate—US), Rev 8/98, Rec 9/98.
  1. Diethylpropion hydrochloride product monograph (Tenuate, Tenuate Dosepan; Hoechst Marion Roussel—Canada). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1655.
  1. Phentermine hydrochloride product monograph (Fastin, SmithKline Beecham—Canada). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 607.
  1. Phentermine resin complex product monograph (Ionamin, Rhône-Poulenc Rorer—Canada). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 798-9.
  1. Panel comment, 1/18/99.
  1. Questions and answers about withdrawal of fenfluramine (Pondimin) and dexfenfluramine (Redux). 1997 Sep 15. Available from: URL: http://www.fda.gov/cder/news/fenphenqa2.htm
  1. FDA announces withdrawal of fenfluramine and dexfenfluramine (Fen-Phen). 1997 Sep 15. Available from: URL: http://www.fda.gov/cder/news/fenphenpr81597.htm
  1. Food and Drug Administration. FDA public health advisory: reports of valvular heart disease in patients receiving concomitant fenfluramine and phentermine. 1997 Jul 8.
  1. Fenfluramine package insert (Pondimin, AH Robins—US), Rev 4/97.
  1. Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996 Aug 29; 335(9): 609-16.
  1. Manufacturer comment, 3/91.
  1. Manufacturer comment, 3/91.
  1. Manufacturer comment, 3/91.
  1. Manufacturer comment, 3/91.
  1. Weintraub M, Bray GA. Drug treatment of obesity. Med Clin North Am 1989 Jan; 73(1): 237-49.
  1. Mazindol package insert (Mazanor, Wyeth Laboratories—US), Rev 3/94, Rec 9/98.
  1. Mazindol package insert (Sanorex, Sandoz—US), Rev 4/96, Rec 9/98.
  1. Inoue S, Egawa M, Satoh S, et al. Clinical and basic aspects of an anorexiant, mazindol, as an antiobesity agent in Japan. Am J Clin Nutr 1992; 55: 199S-202S.
  1. Cleare AJ. Phentermine, psychosis, and family history [letter]. J Clin Psychopharmacol 1996; 16(6): 470-1.
  1. Kokkinos J, Levine SR. Possible association of ischemic stroke with phentermine. Stroke 1993; 24(2): 310-3.
  1. Carney MWP. Diethylpropion and psychosis. Clin Neuropharmacol 1988; 11(2): 183-8.
  1. Rostagno C, Caciolli S, Felici M, et al. Dilated cardiomyopathy associated with chronic consumption of phendimetrazine. Am Heart J 1996; 131(2): 408-9.
  1. Inoue T, Suzuki S. The metabolism of 1-phenyl-2-( N-methyl- N-benzylamino)propane (benzphetamine) and 1-phenyl-2-( N-methyl- N-furfurylamino)propane (furfenorex) in man. Xenobiotica 1986; 16(7): 691-8.
  1. Beckett AH, Stanojcic M. Re-evaluation of the metabolism and excretion of diethylpropion in non-sustained and sustained release formulations. J Pharm Pharmacol 1987; 39: 409-15.
  1. Dugger HA, Heider JG. Biotransformation of mazindol II: absorption and excretion in the dog and man. Drug Metab Dispos 1979; 7(3): 129-31.
  1. Dear Doctor letter 6/26/98, Wyeth-Ayerst.
  1. Cannistra LB, Davis SM, Bauman AG. Valvular heart disease associated with dexfenfluramine [letter]. N Engl J Med 1997 Aug 28; 337(9): 636.
  1. Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: a review and rationale for use. J Am Dent 1983; 107: 623-30.
  1. Ellenhorn MJ, Schonwald S, Ordog G, et al. Ellenhorn's medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins; 1997. p. 349.
  1. Beckett AH, Brookes LG. The metabolism and urinary excretion in man of phentermine, and the influence of N-methyl and p-chloro-substitution. J Pharm Pharmacol 1971 Apr; 23(4): 288-94.
  1. Weissman NJ, Tighe JF, Gottdiener JS, et al. An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. N Engl J Med 1998; 339(11): 725-32.
  1. Phentermine hydrochloride package insert (Pro-Fast, Camall—US), Rev 2/98, Rec 9/98.
  1. Jick H, Vasilakis C, Weinrauch LA, et al. A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation. N Engl J Med 1998; 339(11): 719-24.
  1. Bray GA. Drug treatment of obesity. Am J Clin Nutr 1992; 55: 538S-544S.
  1. Nall KC, Rubin LJ, Lipskind S, et al. Reversible pulmonary hypertension associated with anorexigen use. Am J Med 1991 Jul; 91: 97-9.
  1. Panel comment, 7/96.
  1. Reviewers' responses to monograph revision of 4/99.
  1. Manufacturer comment, 2/25/99.
  1. Plessinger MA. Prenatal exposure to amphetamines: risks and adverse outcomes in pregnancy. Obstet Gynecol Clin North Am 1998 Mar; 25(1): 119-38.
  1. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997 Aug 28; 337(9): 581-8.
  1. Graham DJ, Green L. Further cases of valvular heart disease associated with fenfluramine-phentermine [letter]. N Engl J Med 1997 Aug 28; 337(9): 635.
  1. Khan MA, Herzog CA, St. Peter JV, et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med 1998 Sep 10; 339(11): 713-8.
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