Bontril

Generic Name: Phendimetrazine Tartrate
Class: Amphetamine Derivatives
VA Class: GA751
CAS Number: 50-58-8

Introduction

Amphetamine congener;c anorexigenic agent.a b c d f

Uses for Bontril

Exogenous Obesity

Adjunct to caloric restriction in the short-term management (a few weeks) of exogenous obesity.a b c d f

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Use only for short-term monotherapy; not for use in combination with any other drug for weight loss.100 120 d

Bontril Dosage and Administration

General

  • Teach patient to curtail overeating and consume a suitable diet to help induce and maintain weight loss.c

Administration

Oral Administration

Administer conventional tablets orally 2 or 3 times daily, 1 hour before meals.b c f

Administer extended-release capsules orally once daily, 30–60 minutes before the morning meal.a c d

Dosage

Available as phendimetrazine tartrate; dosage expressed in terms of the salt.b d f

Pediatric Patients

Exogenous Obesity
Conventional Tablets
Oral

Children ≥12 years of age: 35 mg 2 or 3 times daily, given 1 hour before meals.b A dosage of 17.5 mg 2 or 3 times daily may be adequate for some patients.b

Extended-release Capsules
Oral

Children ≥12 years of age: 105 mg once daily, given 30–60 minutes before the morning meal.a

Adults

Exogenous Obesity
Conventional Tablets
Oral

35 mg 2 or 3 times daily, given 1 hour before meals.b c f A dosage of 17.5 mg 2 or 3 times daily may be adequate for some patients.b f

Extended-release Capsules
Oral

105 mg once daily, given 30–60 minutes before the morning meal.a c d

Prescribing Limits

Pediatric Patients

Exogenous Obesity
Oral

Children ≥12 years of age: Maximum 70 mg 3 times daily (as conventional tablets).b

Children ≥12 years of age: Maximum 105 mg once daily (as extended-release capsules).d

Adults

Exogenous Obesity
Oral

Maximum 70 mg 3 times daily (as conventional tablets).b c f

Maximum 105 mg once daily (as extended-release capsules).d

Cautions for Bontril

Contraindications

  • Symptomatic cardiovascular disease, hyperthyroidism, moderate to severe hypertension, pulmonary hypertension, glaucoma, or advanced arteriosclerosis.a b c d f

  • Highly nervous or agitated state or history of drug abuse.a b c d f

  • Concurrent therapy with other CNS stimulantsa b c d f or anorexigenic drugs.d

  • Within 14 days of MAO inhibitor therapy.c

  • Known hypersensitivity or idiosyncrasy to sympathomimetic amines.a b c d f

Warnings/Precautions

Warnings

Primary Pulmonary Hypertension

Risk of primary pulmonary hypertension (frequently fatal), particularly when used in combination with at least one other anorexigenic agent, or in those with a history of receiving at least one other anorexigenic agent.100 d Risk increased by 23-fold when anorexigenic agents are used for >3 months.d Increased risk following repeated courses of phendimetrazine cannot be ruled out.d

Discontinue immediately if new-onset or exacerbation of exertional dyspnea or unexplained symptoms of angina, syncope, or edema of the lower extremities occur, and evaluate for possible pulmonary hypertension.d

Valvular Heart Disease

Valvular heart disease reported following use of some anorexigenic agents (e.g., fenfluramine, dexfenfluramine [both no longer commercially available in the US]), particularly when used for extended periods of time, at higher than recommended dosages, and/or in combination with other anorexigenic agents.d

Abnormal heart valve findings have been reported in some patients receiving phendimetrazine.c 100 120 Weigh potential risks against benefits of therapy.d

Consider performing baseline cardiac evaluation to detect preexisting valvular heart diseases prior to initiation of therapy.d Use not recommended in patients with known heart murmur or valvular heart disease.d Echocardiogram during and after treatment may be useful for detecting any valvular disorders that may occur.d

To limit unwarranted exposure and risks, continue therapy only if patient has achieved satisfactory weight loss (e.g., ≥4 pounds [1.8 kg], or as determined by physician and patient) within first 4 weeks of therapy.d

Tolerance to Anorexigenic Effect

Tolerance to anorexigenic effect usually develops within a few weeks.a b d f When it does, discontinue therapy; do not attempt to increase effect by exceeding recommended dosage.a b d f

CNS Effects

Performance of activities requiring mental alertness or physical coordination may be impaired.a b c d f (See Advice to Patients.)

Abuse Potential

Potential for abuse; habituation or addiction reported with phendimetrazinec and similar drugs (e.g., amphetamines).a b d f

Manifestations of chronic intoxication may include psychosis resembling schizophrenia, severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes.a b d f

Abrupt discontinuance following prolonged high dosage may result in extreme fatigue, depression, and sleep EEG changes.a b d f

Sensitivity Reactions

Tartrazine Sensitivity

Some preparations (e.g., 35-mg conventional tablets manufactured by Sandoz) contain tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.f Incidence of tartrazine sensitivity is low, but it frequently occurs in patients who are sensitive to aspirin.f

General Precautions

Prescribe and dispense in the smallest feasible quantity to minimize possibility of overdosage.a b d f

Hypertension

Use with caution in patients with mild hypertension;a b c d f monitor BP closely.c Contraindicated in those with moderate or severe hypertension.a b c d f

Diabetes Mellitus

Use with caution in patients with diabetes mellitus; insulin requirements may decrease in association with phendimetrazine use and the concomitant dietary regimen and weight loss.c

Specific Populations

Pregnancy

Category C.d e

Whether potential benefits of anorexigenic agents outweigh risks is questionable; use of these agents during pregnancy (especially during the first trimester) probably should be considered a contraindication.c

Lactation

Not known whether phendimetrazine is distributed into milk;d however, because of its low molecular weight, the drug is expected to distribute into milk.e Caution if used in nursing women.d

Pediatric Use

Use not recommended in children <12 years of age.a b c f

Common Adverse Effects

Palpitation, tachycardia, increased BP, overstimulation, restlessness, dizziness, insomnia, agitation, flushing, tremor, sweating, headache, psychosis, blurred vision, dry mouth, diarrhea, constipation, nausea, stomach pain, changes in libido, urinary frequency, dysuria.a b c d f

Interactions for Bontril

Specific Drugs

Drug

Interaction

Comments

Anorexigenic agents

Risk of serious cardiac problemsd

Avoid concomitant use (including with OTC drugs or herbal preparations) (see Contraindications under Cautions); phendimetrazine not recommended for patients who used any anorexigenic agents within prior yeard

CNS stimulants

Concomitant use contraindicateda b d f

Guanethidine (no longer commercially available in the US)

Decreased hypotensive effecta b c d

Insulin

Possible decrease in insulin requirements in patients with diabetes mellitusc

Use concomitantly with cautionc

MAO inhibitors

Potential for hypertensive crisisa b c d f

Phendimetrazine use during or within 14 days of MAO inhibitor use is contraindicatedc

Bontril Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the GI tract following oral administration.c

Duration

Effects persist for about 4 hours.c

Extended-release capsules produce prolonged therapeutic effect.a Effects achieved with one 105-mg extended-release capsule are similar to those achieved with three 35-mg conventional tablets administered at 4-hour intervals.a d

Distribution

Extent

Not known whether phendimetrazine is distributed into milk;d however, because of its low molecular weight, the drug is expected to distribute into milk.e

Elimination

Metabolism

Undergoes limited biotransformation.a d

Elimination Route

Excreted principally in urine.a d

Half-life

Conventional tablets: Approximately 1.9–3.7 hours.a d

Extended-release capsules: Approximately 3.7–9.8 hours.a d

Stability

Storage

Oral

Conventional Tablets and Extended-release Capsules

Tight, light-resistant containersf at 20–25°C.a b d f Protect from moisture.d f

Actions

  • Produces anorexigenic effect and loss of weight.a b c d f

  • Like other amphetamine derivatives, has no primary effect on appetite;a b c d f anorexigenic action probably is secondary to CNS stimulation.c

Advice to Patients

  • Potential for drug to impair mental alertness or physical coordination; caution when driving or operating machinery until effects on individual are known.a b c d f

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., glaucoma, high BP, cardiac disease).a b d f

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a b d f

  • Importance of informing patients of other important precautionary information.a b d f (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule III (C-III) drug.a b c d f

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Phendimetrazine Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

105 mg*

Bontril Slow Release ( C-III)

Valeant

Phendimetrazine Tartrate Extended-release Capsules ( C-III; with povidone)

Sandoz

Tablets

35 mg*

Bontril PDM ( C-III; with isopropyl alcohol and povidone; scored)

Valeant

Phendimetrazine Tartrate Tablets ( C-III; with povidone)

RLC, Sandoz

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 20, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Wyeth-Ayerst. Dear health care professional letter regarding valvular irregularities and primary pulmonary hypertension associated with the use of Plegine. Philadelphia, PA Wyeth-Ayerst; 1998 Jun 15.

101. Deitch MW. Dear health care provider letter: Pondimin and Redux to be voluntarily withdrawn. Philadelphia, PA: Wyeth-Ayerst; 1997 Sep 15.

102. Wyeth-Ayerst. Pondimin and Redux to be voluntarily withdrawn. Philadelphia, PA: 1997 Sep 15. Press release.

103. Lumpkin MM. FDA public health advisory: reports of valvular heart disease in patients receiving concomitant fenfluramine and phentermine. Rockville, MD: Food and Drug Administration; 1997 Jul 8.

104. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997; 337:581-8. [IDIS 391136] [PubMed 9271479]

105. Anon. FDA steps up campaign to discourage off-label “fen/phen” use with public health advisory; agency coordinates message with NEJM, Mayo clinic. FDC Rep. 1997; (Jul 14):4-5.

106. Anon. Knoll Meridia studies continue after Redux, Pondimin withdrawal: lawsuits call for Wyeth to fund medical monitoring of patients exposed to drugs. FDC Rep. 1997; (Sep 22):5.

107. US Food and Drug Administration. Questions and answers about Phen/fen and valvular heart disease. Rockville, MD; 1997 July 8.

108. Plutowski S (Mayo Foundation for Medical Education and Research). Valvular heart disease associated with commonly prescribed diet pills. Rochester, MN; 1997 Jul 8. Press release from website ().

109. Mayo Foundation for Medical Education and Research. Information for physicians regarding pharmacologic therapy for obesity. Rochester, MN; 1997 Jul 7. Press release from website ().

110. Mayo Foundation for Medical Education and Research. Heart valve disease and fen-phen: NEJM waives embargo for Mayo Clinic announcement. Rochester, MN; 1997 Jul 8. Press release from website ().

111. Anon. FDA fenfluramine/Redux epidemiological analysis of HMO records supports findings of valvulopathy in asymptomatic patients reported from five surveys. FDC Rep. 1997; (Sep 15):3-5.

112. Connolly HM, Crary JL, McGoon MD et al. for the Mayo Foundation for Medical Education and Research. Valvular heart disease associated with fenfluramine-phentermine. Rochester, MN; 1997 Jul 8.

113. Mayo Foundation for Medical Education and Research. Information and recommendations for people taking fenfluramine and phentermine. Rochester, MN; 1997 Jul 8.

114. Graham DJ, Green L. Further cases of valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997; 337:635. [IDIS 391141] [PubMed 9280830]

115. Centers for Disease Control and Prevention. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb Mortal Wkly Rep. 1997; 46:1061-6. [IDIS 395477] [PubMed 9385873]

116. Medeva. Ionamin (C-IV) (phentermine resin capsules) prescribing information. Rochester, NY; 1997 Oct.

117. Coyne CT. Dear health care professional letter regarding labeling changes of Ionamin (phentermine resin capsules). Rochester, NY: Medeva; 1997 Aug 8.

118. Coyne CT. Dear doctor or health care professional letter regarding appropriate use of Ionamin (phentermine resin capsules). Rochester, NY: Medeva; 1997 Sep 18.

119. SoRelle R. Fen-phen and risk of valvular disease. Circulation. 1997; 96:1705-6. [PubMed 9323046]

120. Wyeth-Ayerst. Plegine (phendimetrazine tartrate tablets) prescribing information. In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economics Company Inc; 1998(Suppl A):A304.

a. Valeant Pharmaceuticals International. Bontril (phendimetrazine tartrate) slow-release capsules prescribing information. Costa Mesa, CA; 2004 Sep.

b. Valeant Pharmaceuticals International. Bontril PDM (phendimetrazine tartrate) tablets prescribing information. Costa Mesa, CA; 2004 Sep.

c. AHFS Drug Information 2007. McEvoy GK, ed. Phendimetrazine tartrate. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2496-7.

d. Sandoz Inc. Phendimetrazine tartrate extended-release capsules prescribing information. Princeton, NJ; 2006 Mar.

e. Phendimetrazine. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2005:1276.

f. Sandoz Inc. Phendimetrazine tartrate tablets prescribing information. Princeton, NJ; 2006 Mar.

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