These Highlights Do Not Include All The Information Needed To Use Phentermine Hydrochloride Tablets, Usp Safely And Effectively. See Full Prescribing Information For Phentermine Hydrochloride Tablets, Usp.

Phentermine hydrochloride Tablets are 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.

The limited usefulness of agents of this class, including phentermine, [ see Clinical Pharmacology (12.1, 12.2) ] should be measured against possible risk factors inherent in their use such as those described below.

• Dosage should be individualized to obtain an adequate response with the lowest effective dose. ( 2.1)
• Late evening administration should be avoided (risk of insomnia). ( 2.1)
• Phentermine Hydrochloride Tablets can be taken with or without food. ( 2.1)
• Limit the dosage to 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m ²) ( 2.2)

Phentermine Hydrochloride Tablets, USP 37.5 mg are white with blue speckles, capsule-shaped tablets, bisected and debossed with "Є" to the left of bisect and "16" to the right of bisect on one side, and plain on the other side.

Tablets are packaged in bottles of 100 (NDC 63629-1044-1).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

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

Keep out of the reach of children.

• History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension)
• During or within 14 days following the administration of monoamine oxidase inhibitors
• Hyperthyroidism
• Glaucoma
• Agitated states
• History of drug abuse
• Pregnancy [ see Use in Specific Populations (8.1) ]
• Nursing [ see Use in Specific Populations (8.3) ]
• Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines

Phentermine hydrochloride USP is a sympathomimetic amine anorectic. It has the chemical name of α,α,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:

C ₁₀H ₁₅N∙HCl M.W. 185.7

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).

Each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and blue sugar spheres.

• 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)

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.

Teratogenic Effects

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.

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.

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.

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

The following adverse reactions are described, or described in greater detail, in other sections:

• Primary pulmonary hypertension [ see Warnings and Precautions (5.2) ]
• Valvular heart disease [ see Warnings and Precautions (5.3) ]
• Effect on the ability to engage in potentially hazardous tasks [ see Warnings and Precautions (5.5) ]
• Withdrawal effects following prolonged high dosage administration [ see Drug Abuse and Dependence (9.3) ]

The following adverse reactions to phentermine have been identified:

Cardiovascular

Primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevation of blood pressure, ischemic events.

Central Nervous System

Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, psychosis.

Gastrointestinal

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

Allergic

Urticaria.

Endocrine

Impotence, changes in libido.

Phentermine is a Schedule IV controlled substance.

Phentermine is related chemically and pharmacologically to the amphetamines. Amphetamines and other 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 of these drugs to many times than 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. A severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.

The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

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.

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 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.

Tablets containing 37.5 mg phentermine hydrochloride (equivalent to 30 mg phentermine base).

Phentermine Hydrochloride Tablets, USP 37.5 mg are white with blue speckles, capsule-shaped tablets, bisected and debossed with "Є" to the left of bisect and "16" to the right of bisect on one side, and plain on the other side.

Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and dll-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.

Typical actions of amphetamines 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.

Following the administration of phentermine, phentermine reaches peak concentrations (Cmax) after 3 to 4.4 hours.

• Nursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. ( 4, 8.3)
• Pediatric use: Safety and effectiveness not established. ( 8.4)
• Geriatric use: Due to substantial renal excretion, use with caution. ( 8.5)
• Renal Impairment: Avoid use in patients with eGFR less than 15 mL/min/m ² or end-stage renal disease requiring dialysis). ( 8.6)

• 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)

Based on the reported excretion of phentermine in urine, exposure increases can be expected in patients with renal impairment [ see Clinical Pharmacology (12.3) ].

Use caution when administering phentermine to patients with renal impairment. In patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73m ²), limit the dosage of phentermine to 15 mg daily [ see Dosage and Administration (2.2) ]. Phentermine has not been studied in patients with eGFR less than 15 mL/min/1.73m ², including end-stage renal disease requiring dialysis; avoid use in these populations.

Phentermine hydrochloride Tablets are 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.

The limited usefulness of agents of this class, including phentermine, [ see Clinical Pharmacology (12.1, 12.2) ] should be measured against possible risk factors inherent in their use such as those described below.

• Dosage should be individualized to obtain an adequate response with the lowest effective dose. ( 2.1)
• Late evening administration should be avoided (risk of insomnia). ( 2.1)
• Phentermine Hydrochloride Tablets can be taken with or without food. ( 2.1)
• Limit the dosage to 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m ²) ( 2.2)

Phentermine Hydrochloride Tablets, USP 37.5 mg are white with blue speckles, capsule-shaped tablets, bisected and debossed with "Є" to the left of bisect and "16" to the right of bisect on one side, and plain on the other side.

Tablets are packaged in bottles of 100 (NDC 63629-1044-1).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

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

Keep out of the reach of children.

• History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension)
• During or within 14 days following the administration of monoamine oxidase inhibitors
• Hyperthyroidism
• Glaucoma
• Agitated states
• History of drug abuse
• Pregnancy [ see Use in Specific Populations (8.1) ]
• Nursing [ see Use in Specific Populations (8.3) ]
• Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines

• 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)

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.

Teratogenic Effects

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.

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.

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.

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

The following adverse reactions are described, or described in greater detail, in other sections:

• Primary pulmonary hypertension [ see Warnings and Precautions (5.2) ]
• Valvular heart disease [ see Warnings and Precautions (5.3) ]
• Effect on the ability to engage in potentially hazardous tasks [ see Warnings and Precautions (5.5) ]
• Withdrawal effects following prolonged high dosage administration [ see Drug Abuse and Dependence (9.3) ]

The following adverse reactions to phentermine have been identified:

Cardiovascular

Primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevation of blood pressure, ischemic events.

Central Nervous System

Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, psychosis.

Gastrointestinal

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

Allergic

Urticaria.

Endocrine

Impotence, changes in libido.

Phentermine is a Schedule IV controlled substance.

Phentermine is related chemically and pharmacologically to the amphetamines. Amphetamines and other 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 of these drugs to many times than 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. A severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.

The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Phentermine hydrochloride USP is a sympathomimetic amine anorectic. It has the chemical name of α,α,-Dimethylphenethylamine hydrochloride. The structural formula is as follows:

C ₁₀H ₁₅N∙HCl M.W. 185.7

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).

Each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and blue sugar spheres.

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.

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 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.

Tablets containing 37.5 mg phentermine hydrochloride (equivalent to 30 mg phentermine base).

Phentermine Hydrochloride Tablets, USP 37.5 mg are white with blue speckles, capsule-shaped tablets, bisected and debossed with "Є" to the left of bisect and "16" to the right of bisect on one side, and plain on the other side.

Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and dll-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.

Typical actions of amphetamines 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.

Following the administration of phentermine, phentermine reaches peak concentrations (Cmax) after 3 to 4.4 hours.

• Nursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. ( 4, 8.3)
• Pediatric use: Safety and effectiveness not established. ( 8.4)
• Geriatric use: Due to substantial renal excretion, use with caution. ( 8.5)
• Renal Impairment: Avoid use in patients with eGFR less than 15 mL/min/m ² or end-stage renal disease requiring dialysis). ( 8.6)

• 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)

Based on the reported excretion of phentermine in urine, exposure increases can be expected in patients with renal impairment [ see Clinical Pharmacology (12.3) ].

Use caution when administering phentermine to patients with renal impairment. In patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73m ²), limit the dosage of phentermine to 15 mg daily [ see Dosage and Administration (2.2) ]. Phentermine has not been studied in patients with eGFR less than 15 mL/min/1.73m ², including end-stage renal disease requiring dialysis; avoid use in these populations.