Adipex-P

Dosage Forms And Strengths

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

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

Storage And Handling

Available in tablets and capsules containing 37.5 mg phentermine hydrochloride (equivalent to 30 mg phentermine base). Each blue and white, oblong, speckled, scored tablet is debossed with “%medicine_name%” and “9”-“9”. The #3 capsule has an opaque white body and an opaque bright blue cap. Each capsule is imprinted with “%medicine_name%” - “37.5” on the cap and two stripes on the body using dark blue ink.

Tablets are packaged in bottles of 30 (NDC 57844-009-56); 100 (NDC 57844-009-01); and 1000 (NDC 57844-009-10).

Capsules are packaged in bottles of 100 (NDC 57844-019-01).

Store at 20° to 25°C (68° to 77°F).

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

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Manufactured By: Pliva Hrvats ka d.o.o. Zagreb, Croatia. Revised: March 2017

%medicine_name%^® 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 greater than or equal to 30 kg/m², or greater than or equal to 27 kg/m² 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 x 0.0254 = meters.

The limited usefulness of agents of this class, including %medicine_name%^®, should be measured against possible risk factors inherent in their use such as those described below.

Exogenous Obesity

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

The usual adult dose is one capsule (37.5 mg) daily as prescribed by the physician, administered before breakfast or 1 to 2 hours after breakfast for appetite control.

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.

%medicine_name%^® is not recommended for use in pediatric patients less than or equal to 16 years of age.

Late evening medication should be avoided because of the possibility of resulting insomnia.

Dosage In Patients With Renal Impairment

The recommended maximum dosage of %medicine_name%^® is 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m² ). Avoid use of %medicine_name%^® in patients with eGFR less than 15 mL/min/1.73 m² or end-stage renal disease requiring dialysis.

• 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
• Nursing
• Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Coadministration With Other Drug Products For Weight Loss

%medicine_name%^® is indicated only as short-term (a few weeks ) monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with %medicine_name%^® 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 %medicine_name%^® and these drug products is not recommended.

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 %medicine_name%^® 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 may 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.

Valvular Heart Disease

Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricus pid 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 %medicine_name%^® alone cannot be ruled out; there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone.

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.

Effect On The Ability To Engage In Potentially Hazardous Tasks

%medicine_name%^® 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.

Risk Of Abuse And Dependence

%medicine_name%^® is related chemically and pharmacologically to amphetamine (d- and dll-amphetamine) and to other related stimulant drugs that have been extensively abused. The possibility of abuse of %medicine_name%^® 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 and OVERDOSE.

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

Usage With Alcohol

Concomitant use of alcohol with %medicine_name%^® may result in an adverse drug reaction.

Use In Patients With Hypertension

Use caution in prescribing %medicine_name%^® for patients with even mild hypertension (risk of increase in blood pressure).

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.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

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

Use In Specific Populations

Pregnancy

Pregnancy Category X

%medicine_name%^® 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 dll-amphetamine). 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.

Nursing Mothers

It is not known if %medicine_name%^® 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.

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.

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.

Renal Impairment

Based on the reported excretion of phentermine in urine, exposure increases can be expected in patients with renal impairment.

Use caution when administering %medicine_name%^® to patients with renal impairment. In patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m² ), limit the dosage of %medicine_name%^® to 15 mg daily. %medicine_name%^® has not been studied in patients with eGFR less than 15 mL/min/1.73 m², including end-stage renal disease requiring dialysis; avoid use in these populations.

In a single-dose study comparing the exposures after oral administration of a combination capsule of 15 mg phentermine and 92 mg topiramate to the exposures after oral administration of a 15 mg phentermine capsule or a 92 mg topiramate capsule, there is no significant topiramate exposure change in the presence of phentermine. However in the presence of topiramate, phentermine C and AUC increase 13% and 42%, respectively.

Pregnancy Category X

%medicine_name%^® 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 dll-amphetamine). 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.

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

• Primary pulmonary hypertension
• Valvular heart disease
• Effect on the ability to engage in potentially hazardous tasks
• Withdrawal effects following prolonged high dosage administration

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.

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

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.

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.

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 (C ) after 3.0 to 4.4 hours.