Bontril

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

• 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.)

Phendimetrazine is used as part of a short-term plan, along with a low calorie diet, for weight reduction. It is used in obese patients who have not been able to lose weight with diet and exercise alone. Phendimetrazine belongs to the group of medicines known as appetite suppressants.

This medicine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and does not cause any unwanted effects.

Do not use phendimetrazine if you are also using similar medicines, such as benzphetamine, diethylpropion, mazindol, phentermine, Didrex®, or Suprenza™. Also, do not use this medicine if you have used an MAO inhibitor (MAOI) such as Eldepryl®, Marplan®, Nardil®, or Parnate® within the past 14 days. Using these medicines together may cause serious unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may be habit-forming. If you think this medicine is not working properly after you have taken it for a few weeks, do not increase the dose. Instead, check with your doctor.

Stop using this medicine and check with your doctor right away if you notice a decrease in your ability to exercise, if you faint, or if you have chest pain, swelling of your feet or lower legs, or trouble with breathing. These may be symptoms of a very serious heart or lung problem.

This medicine may cause some people to become dizzy, lightheaded, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Do not stop using this medicine unless your doctor tells you to. If you suddenly stop using this medicine, you may feel very tired and depressed.

For diabetic patients: This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

Avoid drinking alcohol while you are using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription and nonprescription (over-the-counter) medicines, dietary supplements, herbal remedies, or medicines for appetite control, asthma, colds, cough, hay fever, and sinus problems.

Phendimetrazine tartrate is a sympathomimetic amine with pharmacological activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.

Drugs of this class used in obesity are commonly known as "anorectics" or "anorexigenics". It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved for example.

Adult obese subjects instructed in dietary management and treated with anorectic drugs, lose more weight on the average than those treated with placebo and diet, as determined in relatively short term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebotreated patients is only a fraction of a pound a week. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The possible origin of the increased weight loss due to the various drug effects is not established. The amount of weight loss associated with the use of an anorectic drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

The major route of elimination is via the kidneys where most of the drug and metabolites are excreted. Some of the drug is metabolized to phenmetrazine and also phendimetrazine-N-oxide. The average half-life of elimination when studied under controlled conditions is about 3.7 hours for both the extended-release and immediate release forms. The absorption half-life of the drug from the immediate release 35 mg phendimetrazine tablets is appreciably more rapid than the absorption rate of the drug from the extended-release formulation.

Phendimetrazine tartrate should not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter preparations and herbal products.

In a case-control epidemiological study, the use of anorectic agents, including phendimetrazine tartrate, was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder. The use of anorectic agents for longer than three months was associated with a 23-fold increase in the risk of developing pulmonary hypertension. Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded.

The onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema suggest the possibility of occurrence of pulmonary hypertension. Under these circumstances, phendimetrazine tartrate should be immediately discontinued, and the patient should be evaluated for the possible presence of pulmonary hypertension.

Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported. Possible contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. However, no cases of this valvulopathy have been reported when phendimetrazine tartrate has been used alone.

The potential risk of possible serious adverse effects such as valvular heart disease and pulmonary hypertension should be assessed carefully against the potential benefit of weight loss. Baseline cardiac evaluation should be considered to detect pre-existing valvular heart diseases or pulmonary hypertension prior to initiation of phendimetrazine treatment. Phendimetrazine tartrate is not recommended in patients with known heart murmur or valvular heart disease. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur. To limit unwarranted exposure and risks, treatment with phendimetrazine tartrate should be continued only if the patient has satisfactory weight loss within the first 4 weeks of treatment (i.e., weight loss of at least 4 pounds, or as determined by the physician and patient).

Tolerance to the anorectic effect of phendimetrazine develops within a few weeks. When this occurs, its use should be discontinued; the maximum recommended dose should not be exceeded.

Use of phendimetrazine tartrate within 14 days following the administration of monoamine oxidase inhibitors may result in a hypertensive crisis.

Abrupt cessation of administration following prolonged high dosage results in extreme fatigue and depression. Because of the effect on the central nervous system, phendimetrazine tartrate may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle; the patient should therefore be cautioned accordingly.

Phendimetrazine tartrate is not recommended for patients who used any anorectic agents within the prior year.

Three-layered green, white and yellow tablet with "B 35" on the scored side and the letter "V" on the other. Bontril® PDM tablets containing 35 mg of phendimetrazine tartrate are available in bottles of 100 (NDC 0187-0497-01) and 1000 (NDC 0187-0497-02).

Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).

DEA Order Form Required.

Distributed by:
Valeant Pharmaceuticals North America
One Enterprise
Aliso Viejo, CA 92656 USA
Manufactured by:
Mallinckrodt, Inc.
Hobart, NY 13788

Printed with food grade ink.

MG #20886
Rev. 10/07
Part No. L2BB01

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of Bontril can be fatal.

Symptoms of a Bontril overdose include nausea, vomiting, diarrhea, stomach cramps, confusion, panic, hallucinations, extreme restlessness, feeling tired or depressed, ringing in your ears, chest pain, slow heart rate, weak pulse, fainting, seizure, or slow breathing (breathing may stop).

Get emergency medical help if you have any of these signs of an allergic reaction to Bontril: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using Bontril and call your doctor at once if you have a serious side effect such as:

• feeling short of breath, even with mild exertion;

• chest pain, feeling like you might pass out;

• swelling in your ankles or feet;

• pounding heartbeats or fluttering in your chest;

• confusion or irritability, unusual thoughts or behavior;

• feelings of extreme happiness or sadness; or

• dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

Less serious Bontril side effects may include:

• feeling restless or hyperactive;

• headache, dizziness, tremors;

• sleep problems (insomnia);

• flushing (warmth, redness, or tingly feeling);

• dry mouth;

• diarrhea or constipation, upset stomach; or

• increased or decreased interest in sex, impotence.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to phendimetrazine: oral capsule extended release, oral tablet

Cardiovascular

Frequency not reported: Valvular heart disease, palpitation, tachycardia, elevated blood pressure, ischemic events, flushing[Ref]

Respiratory

Frequency not reported: Pulmonary hypertension[Ref]

Psychiatric

Frequency not reported: Psychotic state, insomnia, agitation, libido changes[Ref]

Nervous system

Frequency not reported: Overstimulation, restlessness, tremor, dizziness, headache[Ref]

Gastrointestinal

Frequency not reported: Dry mouth, nausea, stomach pain, diarrhea, constipation[Ref]

Genitourinary

Frequency not reported: Urinary frequency, dysuria[Ref]

Ocular

Frequency not reported: Blurred vision[Ref]

Dermatologic

Frequency not reported: Sweating[Ref]

Some side effects of Bontril Slow Release may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.