phentermine hydrochloride 37.5 MG (equivalent to phentermine 30 MG) Oral Tablet
DRUG INTERACTIONS
7 Monoamine oxidase inhibitors: Risk of hypertensive crisis.
( 4 , 7.1 ) Alcohol: Consider potential interaction.
( 7.2 ) Insulin and oral hypoglycemics: Requirements may be altered.
( 7.3 ) Adrenergic neuron blocking drugs: Hypotensive effect may be decreased by phentermine.
( 7.4 ) 7.1 Monoamine Oxidase Inhibitors Use of phentermine is contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors because of the risk of hypertensive crisis .
7.2 Alcohol Concomitant use of alcohol with phentermine may result in an adverse drug reaction .
7.3 Insulin and Oral Hypoglycemic Medications Requirements may be altered [ see Warnings and Precautions (5.9) ].
7.4 Adrenergic Neuron Blocking Drugs Phentermine may decrease the hypotensive effect of adrenergic neuron blocking drugs.
OVERDOSAGE
10 The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.
10.1 Acute Overdosage Manifestations of acute overdosage include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, and panic states.
Fatigue and depression usually follow the central stimulation.
Cardiovascular effects include tachycardia, arrhythmia, hypertension or hypotension, and circulatory collapse.
Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps.
Overdosage of pharmacologically similar compounds has resulted in fatal poisoning usually terminates in convulsions and coma.
Management of acute phentermine hydrochloride 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 (Regitine ® , CIBA) has been suggested on pharmacologic grounds for possible acute, severe hypertension, if this complicates overdosage.
10.2 Chronic Intoxication 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.
See Drug Abuse and Dependence (9.3) .
DESCRIPTION
11 Phentermine hydrochloride USP has the chemical name of α,α,-Dimethylphenethylamine hydrochloride.
The structural formula is as follows: 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 tablet containing 37.5 mg of phentermine hydrochloride (equivalent to 30 mg of phentermine base).
Phentermine hydrochloride tablets contain the inactive ingredients: crospovidone, dibasic calcium phosphate dihydrate, magnesium stearate, povidone, propylene glycol, FD&C Blue #1 Aluminum Lake, shellac glaze, and titanium dioxide.
Chemical Structure
CLINICAL STUDIES
14 In relatively short-term clinical trials, adult obese subjects instructed in dietary management and treated with “anorectic” drugs lost more weight on the average than those treated with placebo and diet.
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 over several 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.
HOW SUPPLIED
16 /STORAGE AND HANDLING Phentermine hydrochloride tablets USP 37.5 mg (equivalent to 30 mg phentermine base) are white with blue specks, oval shaped, scored on one side and debossed MP 273 on the other side.
NDC 12634-687-00 Bottles of 10 NDC 12634-687-01 Bottles of 100 NDC 12634-687-09 Bottles of 35 NDC 12634-687-40 Bottles of 40 NDC 12634-687-42 Bottles of 42 NDC 12634-687-45 Bottles of 45 NDC 12634-687-50 Bottles of 50 NDC 12634-687-52 Blister Pack of 12 NDC 12634-687-54 Blister Pack of 14 NDC 12634-687-57 Blister Pack of 20 NDC 12634-687-58 Blister Pack of 28 NDC 12634-687-59 Blister Pack of 30 NDC 12634-687-60 Bottles of 60 NDC 12634-687-61 Blister Pack of 10 NDC 12634-687-63 Blister Pack of 3 NDC 12634-687-66 Blister Pack of 6 NDC 12634-687-67 Blister Pack of 7 NDC 12634-687-69 Blister Pack of 9 NDC 12634-687-71 Bottles of 30 NDC 12634-687-74 Bottles of 24 NDC 12634-687-78 Bottles of 28 NDC 12634-687-79 Bottles of 25 NDC 12634-687-80 Bottles of 20 NDC 12634-687-81 Bottles of 21 NDC 12634-687-82 Bottles of 12 NDC 12634-687-84 Bottles of 14 NDC 12634-687-85 Bottles of 15 NDC 12634-687-90 Bottles of 90 NDC 12634-687-91 Blister Pack of 1 NDC 12634-687-92 Bottles of 2 NDC 12634-687-93 Bottles of 3 NDC 12634-687-94 Bottles of 4 NDC 12634-687-95 Bottles of 5 NDC 12634-687-96 Bottles of 6 NDC 12634-687-97 Bottles of 7 NDC 12634-687-98 Bottles of 8 NDC 12634-687-99 Bottles of 9 Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room Temperature] DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
Keep out of the reach of children.
GERIATRIC USE
8.5 Geriatric Use In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
DOSAGE FORMS AND STRENGTHS
3 Tablets containing 37.5 mg phentermine hydrochloride (equivalent to 30 mg phentermine base).
Tablets containing 37.5 mg phentermine hydrochloride.
( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and d / l-amphetamine).
Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics.” It has not been established that the primary action of such drugs in treating obesity is one of appetite suppression since other central nervous system actions, or metabolic effects, may also be involved.
INDICATIONS AND USAGE
1 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/m 2 , or ≥ 27 kg/m 2 in the presence of other risk factors (e.g., controlled 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 × 0.0254 = meters.
BODY MASS INDEX (BMI), kg/m 2 The limited usefulness of agents of this class, including phentermine hydrochloride tablets, [ see Clinical Pharmacology (12.1 , 12.2) ] should be measured against possible risk factors inherent in their use such as those described below.
Phentermine hydrochloride is a sympathomimetic amine anorectic indicated as a short-term adjunct (a few weeks) 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/m 2 , or ≥ 27 kg/m 2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia).
( 1 ) The limited usefulness of agents of this class, including phentermine hydrochloride, should be measured against possible risk factors inherent in their use.
( 1 ) BMI figure
PEDIATRIC USE
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Because pediatric obesity is a chronic condition requiring long-term treatment, the use of this product, approved for short-term therapy, is not recommended.
PREGNANCY
8.1 Pregnancy Teratogenic Effects Pregnancy category X Phentermine is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm.
A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy.
Phentermine has pharmacologic activity similar to amphetamine (d- and d / l-amphetamine) [ see Clinical Pharmacology (12.1) ].
Animal reproduction studies have not been conducted with phentermine.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
NUSRING MOTHERS
8.3 Nursing Mothers It is not known if phentermine is excreted in human milk; however, other amphetamines are present in human milk.
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.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Coadministration with other drugs for weight loss is not recommended (safety and efficacy of combination not established).
( 5.1 ) Rare cases of primary pulmonary hypertension have been reported.
Phentermine should be discontinued in case of new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema.
( 5.2 ) Rare cases of serious regurgitant cardiac valvular disease have been reported.
( 5.3 ) Tolerance to the anorectic effect usually develops within a few weeks.
If this occurs, phentermine should be discontinued.
The recommended dose should not be exceeded.
( 5.4 ) Phentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle.
( 5.5 ) Risk of abuse and dependence.
The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.
( 5.6 ) Concomitant alcohol use may result in an adverse drug reaction.
( 5.7 ) Use caution in patients with even mild hypertension (risk of increase in blood pressure).
( 5.8 ) A reduction in dose of insulin or oral hypoglycemic medication may be required in some patients.
( 5.9 ) 5.1 Coadministration With Other Drug Products for Weight Loss Phentermine hydrochloride tablets are indicated only as short-term (a few weeks) 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 prescribed drugs, over-the-counter preparations, and herbal products, or serotonergic agents such as selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established.
Therefore, coadministration of phentermine and these drug products is not recommended.
5.2 Primary Pulmonary Hypertension 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 symptom 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, and patients should be evaluated for the possible presence of pulmonary hypertension.
5.3 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 possible role of phentermine in 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.
5.4 Development of Tolerance, Discontinuation in Case of Tolerance When tolerance to the anorectant effect develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.
5.5 Effect on the Ability to Engage in Potentially Hazardous Tasks 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.
5.6 Risk of Abuse and Dependence Phentermine is related chemically and pharmacologically to amphetamine (d- and d/l-amphetamine) and other related stimulant drugs have been extensively abused.
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.
See Drug Abuse and Dependence (9) and Overdosage (10) .
The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.
5.7 Usage With Alcohol Concomitant use of alcohol with phentermine may result in an adverse drug reaction.
5.8 Use in Patients With Hypertension Use caution in prescribing phentermine for patients with even mild hypertension (risk of increase in blood pressure).
5.9 Use in Patients on Insulin or Oral Hypoglycemic Medications for Diabetes Mellitus A reduction in insulin or oral hypoglycemic medications in patients with diabetes mellitus may be required.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Patients must be informed that phentermine hydrochloride is 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, and that coadministration of phentermine with other drugs for weight loss is not recommended [ see Indications and Usage (1) and Warnings and Precautions (5.1) ].
Patients must be instructed on how much phentermine to take, and when and how to take it [ see Dosage and Administration (2) ].
Advise pregnant women and nursing mothers not to use phentermine [ see Use in Specific Populations (8.1 , 8.3) ].
Patients must be informed about the risks of use of phentermine (including the risks discussed in Warnings and Precautions), about the symptoms of potential adverse reactions and when to contact a physician and/or take other action.
The risks include, but are not limited to: -Development of primary pulmonary hypertension [ see Warnings and Precautions (5.2) ] -Development of serious valvular heart disease [ see Warnings and Precautions (5.3) ] -Effects on the ability to engage in potentially hazardous tasks [ see Warnings and Precautions (5.5) ] -The risk of an increase in blood pressure [ see Warnings and Precautions (5.8) and Adverse Reactions (6) ] -The risk of interactions [ see Contraindications (4) , Warnings and Precautions (5.7 , 5.9) and Drug Interactions (7) ] See also, for example, Adverse Reactions (6) and Use in Specific Populations (8) .
The patients must also be informed about -the potential for developing tolerance and actions if they suspect development of tolerance [ see Warnings and Precautions (5.4) ] and -the risk of dependence and the potential consequences of abuse [ see Warnings and Precautions (5.6) , Drug Abuse and Dependence (9) , and Overdosage (10) ].
Tell patients to keep phentermine in a safe place to prevent theft, accidental overdose, misuse or abuse.
Selling or giving away phentermine may harm others and is against the law.
Regitine ® is a registered trademark of CIBA PHARMACEUTICAL PRODUCTS, INC.
DOSAGE AND ADMINISTRATION
2 Dosage should be individualized to obtain an adequate response with the lowest effective dose.
( 2 ) Late evening administration should be avoided (risk of insomnia).
( 2 ) Phentermine hydrochloride tablets can be taken with or without food.
( 12.3 ) Exogenous Obesity Dosage should be individualized to obtain an adequate response with the lowest effective dose.
The usual adult dose is one tablet (37.5 mg) daily, as prescribed by the physician, administered before breakfast or 1 to 2 hours after breakfast.
The dosage may be adjusted to the patient’s need.
For some patients, half tablet (18.75 mg) daily may be adequate, while in some cases it may be desirable to give half tablets (18.75 mg) two times a day.
Phentermine hydrochloride is not recommended for use in pediatric patients ≤ 16 years of age.
Late evening medication should be avoided because of the possibility of resulting insomnia.