ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are described, or described in greater detail, in other sections:oPrimary pulmonary hypertension see Warnings and Precautions 5.2 )] oValvular heart disease see Warnings and Precautions 5.3 )] oEffect on the ability to engage in potentially hazardous tasks see Warnings and Precautions 5.5 )] oWithdrawal 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 (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. oEffect on the ability to engage in potentially hazardous tasks see Warnings and Precautions 5.5 )].

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Phentermine is sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and ll-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. 12.2 Pharmacodynamics. Typical 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.. 12.3 Pharmacokinetics. Following the administration of Phentermine, Phentermine reaches peak concentrations (Cmax) after to 4.4 hours.Specific PopulationsRenal Impairment Phentermine was not studied in patients with renal impairment. The literature reported cumulative urinary excretion of phentermine under uncontrolled urinary pH conditions is 62% to 85%. Exposure increases can be expected in patients with renal impairment. Use caution when administering phentermine to patients with renal impairment.Drug InteractionsIn single-dose study comparing the exposures after oral administration of combination capsule of 15 mg Phentermine and 92 mg topiramate to the exposures after oral administration of 15 mg Phentermine capsule or 92 mg topiramate capsule, there is no significant topiramate exposure change in the presence of Phentermine. However, in the presence of topiramate, Phentermine max and AUC increase 13% and 42%, respectively.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES 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 fraction of pound 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 few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

DESCRIPTION SECTION.

11 DESCRIPTION. Phentermine Hydrochloride USP has the chemical name of -Dimethylphenethylamine hydrochloride. The structural formula is as follows:Phentermine Hydrochloride is 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 and magnesium stearate. In addition, the 15 mg capsules contain D&C Yellow 10, FD&C Blue 1, FD&C Red 3, FD&C Red 40, titanium dioxide and the 30 mg capsules contain D&C Yellow 10, FD&C Red 3, titanium dioxide.b) bead-filled capsules containing 30 mg Phentermine hydrochloride (equivalent to 24 mg Phentermine) and inactive ingredients: corn starch, sucrose, hypromellose, povidone, and talc. In addition, the capsule contains FD&C blue 1/Brilliant blue FCF Aluminum Lake, D&C red 28 and gelatin.. image description.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED Phentermine Hydrochloride capsules, USP are available as follows:Phentermine Hydrochloride capsules, USP 15 mg are supplied as gray opaque cap, rich yellow opaque body with black imprint K 26 on both the cap and body, filled with powder.Bottles of 30, NDC 10702-026-03Bottles of 100, NDC 10702-026-01Bottles of 1000, NDC 10702-026-10Phentermine Hydrochloride capsules, USP 30 mg are supplied as rich yellow opaque cap, rich yellow opaque body with black imprint K 27 on both the cap and body, filled with powder.Bottles of 30, NDC 10702-027-03Bottles of 100, NDC 10702-027-01Bottles of 1000, NDC 10702-027-10Phentermine Hydrochloride capsules, USP 30 mg are supplied as blue cap, natural body with black imprint K 28 on both the cap and body, filled with white and blue colored beads.Bottles of 30, NDC 10702-028-03Bottles of 100, NDC 10702-028-01Bottles of 1000, NDC 10702-028-10Store at 20 to 25C (68 to 77F) with excursions permitted between 15 to 30C (59 to 86F) [See USP Controlled Room Temperature]. Protect from moisture. Dispense in tight, light resistant container as defined in the USP, with child-resistant closure (as required). Protect from moisture. Keep out of the reach of children.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Phentermine Hydrochloride, USP 15 mg and 30 mg is indicated as short-term (a few weeks) adjunct in 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 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). Below is chart of Body Mass Index (BMI) based on various heights and weights.BMI is calculated by taking the patients weight, in kilograms (kg), divided by the patients 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 hydrochloride, see CLINICAL PHARMACOLOGY 12.1 12.2 )] should be measured against possible risk factors inherent in their use such as those described below. image description.

OVERDOSAGE SECTION.

10 OVERDOSAGE. 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 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 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(R), 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 ).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 30mg Bottle Label Blenheim Pharmacal, Inc.NDC 10544-620-21Phentermine Hydrochloride Capsules, USP30mg CIV21 Count Bottle. Label 30mg 21ct.

SPL UNCLASSIFIED SECTION.

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Phentermine Hydrochloride Capsules, USP safely and effectively. See full prescribing information for Phentermine Hydrochloride Capsules, USP.Phentermine Hydrochloride Capsules, USP CIV for oral useINDICATIONS AND USAGEPhentermine Hydrochloride is sympathomimetic amine anorectic indicated as short-term adjunct (a few weeks) in 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 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) DOSAGE AND ADMINISTRATIONDosage should be individualized to obtain an adequate response with the lowest effective dose.DOSAGE FORMS AND STRENGTHSoCapsules containing 15 mg and 30 mg Phentermine Hydrochloride. 3) CONTRAINDICATIONS oHistory of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension) 4) oDuring or within 14 days following the administration of monoamine oxidase inhibitors 4) oHyperthyroidism 4) oGlaucoma 4) oAgitated states 4) oHistory of drug abuse 4) oPregnancy 4, 8.1) oNursing 4, 8.3) oKnown hypersensitivity, or idiosyncrasy to the sympathomimetic amines 4) WARNINGS AND PRECAUTIONS oCo-administration with other drugs for weight loss is not recommended (safety and efficacy of combination not established). 5.1) oRare 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) oRare cases of serious regurgitant cardiac valvular disease have been reported. 5.3) oTolerance to the anorectic effect usually develops within few weeks. If this occurs, phentermine should be discontinued. The recommended dose should not be exceeded. 5.4) oPhentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving motor vehicle. 5.5) oRisk 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) oConcomitant alcohol use may result in an adverse drug reaction. 5.7) oUse caution in patients with even mild hypertension (risk of increase in blood pressure). 5.8) oA reduction in dose of insulin or oral hypoglycemic medication may be required in some patients. 5.9) ADVERSE REACTIONSAdverse events have been reported in the cardiovascular, central nervous, gastrointestinal, allergic, and endocrine systems. 6) To report SUSPECTED ADVERSE REACTIONS, contact KVK-TECH, Inc., at 215-579-1842 or customerservicekvktech.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.DRUG INTERACTIONSoMonoamine oxidase inhibitors: Risk of hypertensive crisis. 4, 7.1) oAlcohol: Consider potential interaction 7.2) oInsulin and oral hypoglycemics: Requirements may be altered. 7.3) oAdrenergic neuron blocking drugs: Hypotensive effect may be decreased by phentermine. 7.4) USE IN SPECIFIC POPULATIONS oNursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. 4, 8.3) oPediatric use: Safety and effectiveness not established. 8.4) oGeriatric use: Due to substantial renal excretion, use with caution. 8.5) oUse caution when administering phentermine to patients with renal impairment 8.6) See 17 for PATIENT COUNSELING INFORMATIONRevised: 12/2012FULL PRESCRIBING INFORMATION: CONTENTS Sections or subsections omitted from the full prescribing information are not listed INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Co-administration With Other Drug Products for Weight Loss5.2 Primary Pulmonary Hypertension5.3 Valvular Heart Disease5.4 Development of Tolerance, Discontinuation in Case of Tolerance5.5 Effect on the Ability to Engage in Potentially Hazardous Tasks5.6 Risk of Abuse and Dependence5.7 Usage With Alcohol5.8 Use in Patients With Hypertension5.9 Use in Patients on Insulin or Oral Hypoglycemic Medications for Diabetes Mellitus6 ADVERSE REACTIONS7 DRUG INTERACTIONS7.1 Monoamine Oxidase Inhibitors7.2 Alcohol7.3 Insulin and Oral Hypoglycemic Medications7.4 Adrenergic Neuron Blocking Drugs8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal Impairment9 DRUG ABUSE AND DEPENDENCE9.1 Controlled Substance9.2 Abuse9.3 Dependence10 OVERDOSAGE10.1 Acute Overdosage10.2 Chronic Intoxication11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATIONFULL PRESCRIBING INFORMATION. oHistory of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension) 4) oDuring or within 14 days following the administration of monoamine oxidase inhibitors 4) oDuring or within 14 days following the administration of monoamine oxidase inhibitors 4) oCo-administration with other drugs for weight loss is not recommended (safety and efficacy of combination not established). 5.1) oRare 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) oRare 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) oRare cases of serious regurgitant cardiac valvular disease have been reported. 5.3) oRare cases of serious regurgitant cardiac valvular disease have been reported. 5.3) oTolerance to the anorectic effect usually develops within few weeks. If this occurs, phentermine should be discontinued. The recommended dose should not be exceeded. 5.4) oTolerance to the anorectic effect usually develops within few weeks. If this occurs, phentermine should be discontinued. The recommended dose should not be exceeded. 5.4) oPhentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving motor vehicle. 5.5) oPhentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving motor vehicle. 5.5) oRisk 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) oRisk 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) oUse caution in patients with even mild hypertension (risk of increase in blood pressure). 5.8) oA reduction in dose of insulin or oral hypoglycemic medication may be required in some patients. 5.9) oA reduction in dose of insulin or oral hypoglycemic medication may be required in some patients. 5.9) oAdrenergic neuron blocking drugs: Hypotensive effect may be decreased by phentermine. 7.4) oNursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. 4, 8.3) oUse caution when administering phentermine to patients with renal impairment 8.6).