Phentermine Hydrochloride Capsules USP

PHENTERMINE HYDROCHLORIDE - phentermine hydrochloride capsule 
Sandoz Inc.

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Phentermine Hydrochloride Capsules USP

DESCRIPTION

Phentermine hydrochloride has the chemical name of α,α-Di-methylphenethylamine hydrochloride. The structural formula is as follows:

Chemical Structure

C10H15N•HCl M.W. 185.70

Phentermine hydrochloride is a white, odorless, hygroscopic, crystalline powder which is soluble in water and lower alcohols; slightly soluble in chloroform and insoluble in ether.

Phentermine hydrochloride, an anorectic agent for oral administration, is available as:

a) powder-filled capsules containing 15 mg phentermine hydrochloride (equivalent to 12 mg phentermine) or 30 mg phentermine hydrochloride (equivalent to 24 mg phentermine) and inactive ingredients: corn starch, gelatin, lactose monohydrate, magnesium stearate, silicon dioxide and sodium lauryl sulfate and

b) pellet-filled capsules containing 30 mg phentermine hydrochloride (equivalent to 24 mg phentermine) and inactive ingredients: corn starch, gelatin, pharmaceutical glaze, povidone, silicon dioxide, sodium lauryl sulfate and sucrose.

In addition, the 15 mg capsules contain FD&C blue No. 1, FD&C red No. 3, D&C yellow No. 10, FD&C red No. 40, titanium dioxide; the black 30 mg capsules contain FD&C blue No. 1, FD&C yellow No. 6, FD&C red No. 40; the red/black 30 mg capsules contain FD&C blue No. 1, FD&C red No. 3, FD&C yellow No. 6, FD&C red No. 40, titanium dioxide; the yellow 30 mg capsules contain FD&C red No. 3, D&C yellow No. 10, titanium dioxide; and the blue/clear 30 mg capsules contain FD&C blue No. 1, D&C red No. 28.

CLINICAL PHARMACOLOGY

Phentermine is a sympathomimetic amine with pharmacologic 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 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 placebo-treated 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 origins of the increased weight loss due to the various drug effects are 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 drugs 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.

INDICATIONS AND USAGE

Phentermine hydrochloride is indicated as a short-term (a few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity for patients with an initial body mass index ≥ 30 kg/m2 or ≥ 27 kg/m2 in the presence of other risk factors (e.g., hypertension, diabetes, hyperlipidemia).

Below is a chart of Body Mass Index (BMI) based on various heights and weights.

BMI is calculated by taking the patient’s weight, in kilograms (kg), divided by the patient’s height, in meters (m), squared. Metric conversions are as follows: pounds ÷ 2.2 = kg; inches x 0.0254 = meters.


BOBY MASS INDEX (BMI), kg/m2 Height (feet, inches)
Weight (pounds)5'0"5'3"5'6"5'9"6'0"6'3"
140272523211918
150292724222019
160312826242220
170333028252321
180353229272523
190373431282624
200393632302725
210413734312926
220433936333028
230454137343129
240474339363330
250494440373431

The limited usefulness of agents of this class (see CLINICAL PHARMACOLOGY) should be measured against possible risk factors inherent in their use such as those described below.

CONTRAINDICATIONS

Advanced arteriosclerosis, cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.

Agitated states.

Patients with history of drug abuse.

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).

WARNINGS

Phentermine hydrochloride capsules are indicated only as short-term monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with phentermine and any other drug products for weight loss, including selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established. Therefore, co-administration of these drug products for weight loss is not recommended.

Primary Pulmonary Hypertension (PPH) - a rare, frequently fatal disease of the lungs - has been reported to occur in patients receiving a combination of phentermine with fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of phentermine alone cannot be ruled out; there have been rare cases of PPH in patients who reportedly have taken phentermine alone. The initial symptoms of PPH is usually dyspnea. Other initial symptoms include: angina pectoris, syncope or lower extremity edema. Patients should be advised to report immediately any deterioration in exercise tolerance. Treatment should be discontinued in patients who develop new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema.

Valvular Heart Disease

Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricuspid valves, has been reported in otherwise healthy persons who had taken a combination of phentermine with fenfluramine or dexfenfluramine for weight loss. The etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. The possibility of an association between valvular heart disease and the use of phentermine alone cannot be ruled out; there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone.

Tolerance to the anorectic effect usually develops within a few weeks. When this occurs, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.

Phentermine 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.

Usage with Alcohol

Concomitant use of alcohol with phentermine may result in an adverse drug interaction.

PRECAUTIONS

General

Caution is to be exercised in prescribing phentermine hydrochloride for patients with even mild hypertension. Insulin requirements in diabetes mellitus may be altered in association with the use of phentermine and the concomitant dietary regimen.

Phentermine may decrease the hypotensive effect of guanethidine. The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies have not been performed with phentermine hydrochloride to determine the potential for carcinogenesis, mutagenesis or impairment of fertility.

Pregnancy

Teratogenic Effects

 Pregnancy Category C 

 Animal reproduction studies have not been conducted with phentermine hydrochloride. It is also not known whether phentermine hydrochloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Phentermine should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS

Cardiovascular: Primary pulmonary hypertension and/or regurgitant cardiac valvular disease (see WARNINGS), palpitation, tachycardia, elevation of blood pressure.

Central Nervous System: Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache; rarely psychotic episodes at recommended doses.

Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances.

Allergic: Urticaria.

Endocrine: Impotence, changes in libido.

DRUG ABUSE AND DEPENDENCE

Phentermine is related chemically and pharmacologically to the amphetamines. Amphetamines and related stimulant drugs have been extensively abused and the possibility of abuse of phentermine should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. Abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social dysfunction. There are reports of patients who have increased the dosage to many times that recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxications is psychosis, often clinically indistinguishable from schizophrenia.

Overdosage

Manifestations of acute overdosage with phentermine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.

Management of acute phentermine intoxication is largely symptomatic and includes lavage and sedation with a barbiturate. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard. Acidification of the urine increases phentermine excretion. Intravenous phentolamine has been suggested for possible acute, severe hypertension, if this complicates phentermine overdosage.

DOSAGE AND ADMINISTRATION

Dosage should be individualized to obtain an adequate response with the lowest effective dose.

Exogenous Obesity

The usual dosage is 15 mg to 30 mg at approximately 2 hours after breakfast for appetite control. Late evening medication should be avoided because of the possibility of resulting insomnia. Administration of one capsule (30 mg) daily has been found to be adequate in depression of the appetite for 12 to 14 hours.

Phentermine is not recommended for use in patients 16 years of age and under.

HOW SUPPLIED

Phentermine hydrochloride capsules are supplied as:

15 mg capsules, grey/yellow; imprinted E 882

30 mg capsules, yellow; imprinted E 647

30 mg capsules, blue/clear, blue/white pellets, imprinted E 5000 and are available in bottles of 100 and 1000.

Storage

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Manufactured for

Sandoz Inc.

Princeton, NJ 08540

Manufactured by

Epic Pharma, LLC

Laurelton, NY 11413

OS7330

Rev. 10/08

MF5000REV10/08

MG #16643

Phentermine Hydrochloride Capsules USP, 15 mg x 100 Capsules - Label

NDC 0185-0644-01

Phentermine Hydrochloride Capsules USP

15 mg

Grey/Yellow

Rx only

100 Capsules

Sandoz

15 mg x 100 Capsules - Label

Phentermine Hydrochloride Capsules USP, 30 mg x 100 Capsules - Label

NDC 0185-5000-01

Phentermine Hydrochloride Capsules USP

30 mg

Blue/Clear

Rx only

100 Capsules

Sandoz

30 mg x 100 Capsules - Label

Phentermine Hydrochloride Capsules USP, 30 mg x 100 Capsules - Label

NDC 0185-0647-01

Phentermine Hydrochloride Capsules USP

30 mg

Yellow

Rx only

100 Capsules

Sandoz

30 mg Yellow x 100 Capsules - Label


PHENTERMINE HYDROCHLORIDE 
phentermine hydrochloride   capsule
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)0185-0644
Route of AdministrationORALDEA ScheduleCIV    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
PHENTERMINE HYDROCHLORIDE (PHENTERMINE) PHENTERMINE HYDROCHLORIDE15 mg
Inactive Ingredients
Ingredient NameStrength
STARCH, CORN 
GELATIN 
LACTOSE MONOHYDRATE 
MAGNESIUM STEARATE 
SILICON DIOXIDE 
SODIUM LAURYL SULFATE 
FD&C BLUE NO. 1 
FD&C RED NO. 3 
D&C YELLOW NO. 10 
FD&C RED NO. 40 
TITANIUM DIOXIDE 
Product Characteristics
ColorGRAY (Gray/Yellow) Score no score
ShapeCAPSULESize22mm
FlavorImprint Code E882
Contains    
Packaging
#NDCPackage DescriptionMultilevel Packaging
10185-0644-01100 CAPSULE In 1 BOTTLENone
20185-0644-101000 CAPSULE In 1 BOTTLENone

Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA08719006/12/1981

PHENTERMINE HYDROCHLORIDE 
phentermine hydrochloride   capsule
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)0185-5000
Route of AdministrationORALDEA ScheduleCIV    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
PHENTERMINE HYDROCHLORIDE (PHENTERMINE) PHENTERMINE HYDROCHLORIDE30 mg
Inactive Ingredients
Ingredient NameStrength
STARCH, CORN 
GELATIN 
POVIDONE 
SILICON DIOXIDE 
SODIUM LAURYL SULFATE 
SUCROSE 
FD&C BLUE NO. 1 
D&C RED NO. 28 
Product Characteristics
ColorBLUE (Blue/Clear) Score no score
ShapeCAPSULESize22mm
FlavorImprint Code E5000
Contains    
Packaging
#NDCPackage DescriptionMultilevel Packaging
10185-5000-01100 CAPSULE In 1 BOTTLENone
20185-5000-101000 CAPSULE In 1 BOTTLENone

Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA08719006/12/1981

PHENTERMINE HYDROCHLORIDE 
phentermine hydrochloride   capsule
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)0185-0647
Route of AdministrationORALDEA ScheduleCIV    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
PHENTERMINE HYDROCHLORIDE (PHENTERMINE) PHENTERMINE HYDROCHLORIDE30 mg
Inactive Ingredients
Ingredient NameStrength
STARCH, CORN 
GELATIN 
LACTOSE MONOHYDRATE 
MAGNESIUM STEARATE 
SILICON DIOXIDE 
SODIUM LAURYL SULFATE 
FD&C RED NO. 3 
D&C YELLOW NO. 10 
TITANIUM DIOXIDE 
Product Characteristics
ColorYELLOWScore no score
ShapeCAPSULESize22mm
FlavorImprint Code E647
Contains    
Packaging
#NDCPackage DescriptionMultilevel Packaging
10185-0647-01100 CAPSULE In 1 BOTTLENone
20185-0647-101000 CAPSULE In 1 BOTTLENone

Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA08719006/12/1981

Labeler - Sandoz Inc. (614842560)
Establishment
NameAddressID/FEIOperations
Epic Pharma, LLC827915443MANUFACTURE, ANALYSIS
Revised: 06/2010Sandoz Inc.