Suprenza

Dosage Forms And Strengths

Orally disintegrating tablets (ODT) containing 15 mg, 30 mg, or 37.5 mg phentermine hydrochloride (equivalent to 12 mg, 24 mg, or 30 mg phentermine base, respectively). The tablets are not scored. The 15 mg ODT is a yellow with blue spots round tablet embossed with AX4 on one side. The 30 mg ODT is a yellow round tablet embossed with AX7 on one side. The 37.5 mg ODT is a white with blue spots round tablet embossed with AX8 on one side.

Storage And Handling

Available as orally disintegrating tablets (ODT) containing 15 mg, 30 mg, or 37.5 mg of phentermine hydrochloride (equivalent to 12 mg, 24 mg, or 30 mg phentermine base, respectively). The tablets are not scored. The 15 mg ODT is a yellow with blue spots round tablet embossed with AX4 on one side. The 30 mg ODT is a yellow round tablet embossed with AX7 on one side. The 37.5 mg ODT is a white with blue spots round tablet embossed with AX8 on one side.

Suprenza is available as described in Table 2.

Table 2: Suprenza Orally Disintegrating Tablet Presentations

Suprenza 15 mg, 30 mg, and 37.5 mg ODT are packaged in bottles of 30.

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 out of the reach of children.

Manufactured for Akrimax Pharmaceuticals, LLC Cranford, NJ 07016. by: Alpex Pharma SA, Lugano, Switzerland. Marketed and Distributed by: Akrimax Pharmaceuticals, LLC Cranford, NJ 07016. Revised: 06/2013

Suprenza 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.

BODY MASS INDEX (BMI), kg/m²

The limited usefulness of agents of this class, including Suprenza, 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 tablet as prescribed by the physician, administered in the morning, with or without food. Suprenza 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.

With dry hands, gently remove the Suprenza (phentermine hydrochloride ODT) tablet from the bottle. Immediately place the Suprenza tablet on top of the tongue where it will dissolve, then swallow with or without water.

• 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

Suprenza is indicated only as short-term (a few weeks) monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with Suprenza 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 Suprenza 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 Suprenza 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 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 Suprenza 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

Suprenza 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

Suprenza 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 Suprenza 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 OVERDOSAGE.

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 Suprenza may result in an adverse drug reaction.

Use in Patients with Hypertension

Use caution in prescribing Suprenza 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.

Risk of Allergic Reactions due to Tartrazine

Suprenza 15 mg and 30 mg ODT contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Use In Specific Populations

Pregnancy

Pregnancy Category X

Suprenza 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 dllamphetamine) . 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 Suprenza 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

Suprenza was not studied in patients with 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 Suprenza to patients with renal impairment.

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 Cmax and AUC increase 13% and 42%, respectively.

Pregnancy Category X

Suprenza 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 dllamphetamine) . 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. 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.

In terms of rate and extent of exposure, phentermine orally disintegrating tablets are equivalent to phentermine capsules and tablets administered under fasting conditions.

Following the administration of the oral disintegrating tablet (ODT), phentermine reaches peak concentrations (Cmax) after 3.0 to 4.4 hours. Swallowing the ODT after disintegration with or without water did not affect the extent (AUC) of phentermine exposure.

Administration of the ODT after a high fat/high calorie breakfast decreased the Cmax of phentermine by approximately 5% and the AUC by approximately 12%. Despite the decrease in Cmax and AUC, phentermine ODT can be administered with or without food.

Swallowing the ODT without prior disintegration decreased the Cmax of phentermine by approximately 7% and the AUC by approximately 8% compared to swallowing the ODT after disintegration.