PHENDIMETRAZINE TARTRATE- phendimetrazine tartrate tablet 
Apotheca Inc.

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DESCRIPTION

Phendimetrazine tartrate, as the dextro isomer, has the chemical name of (2 S, 3 S)-3, 4-Dimethyl-2-phenylmorpholine L-(+)-tartrate (1:1).

The structural formula is:

phendimetrazine tartrate chemical structure

Phendimetrazine tartrate is a white, odorless crystalline powder. It is freely soluble in water; sparingly soluble in warm alcohol, insoluble in chloroform, acetone, ether and benzene.

Each tablet, for oral administration, contains 35 mg of phendimetrazine tartrate. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dibasic calcium phosphate dihydrate, magnesium stearate, and microcrystalline cellulose.

CLINICAL PHARMACOLOGY

Phendimetrazine tartrate is a sympathomimetic amine with pharmacological activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions 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.

Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics”. It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved for example.

Adult obese subjects instructed in dietary management and treated with anorectic drugs, lose more weight on the average than those treated with placebo and diet, as determined in relatively short term clinical trials.

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 origin of the increased weight loss due to the various drug effects is 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 drug 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 in 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.

The major route of elimination is via the kidneys where most of the drug and metabolites are excreted. Some of the drug is metabolized to phenmetrazine and also phendimetrazine-N-oxide. The average half-life of elimination when studied under controlled conditions is about 3.7 hours for both the extended-release and immediate release forms. The absorption half-life of the drug from the immediate release 35 mg phendimetrazine tablets is appreciably more rapid than the absorption rate of the drug from the extended-release formulation.

INDICATIONS AND USAGE

Phendimetrazine tartrate tablets are indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction in patients with an initial body mass index (BMI) of 30 kg/m 2 or higher who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone. 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
WeightHeight (feet, inches)
(pounds)5'0"5'3"5'6"5'9"6'0"6'3"
140272523211918
150292724222019
160312826242220
170333028252321
180353229272523
190373431282624
200393632302725
210413734312926
220433936333028
230454137343129
240474339363330
250494440373431

Phendimetrazine tartrate is indicated for use as monotherapy only.

CONTRAINDICATIONS

Known hypersensitivity or idiosyncratic reactions to sympathomimetics.

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate and severe hypertension, hyperthyroidism, and glaucoma.

Highly nervous or agitated patients.

Patients with a history of drug abuse.

Patients taking other CNS stimulants, including monoamine oxidase inhibitors.

WARNINGS

Phendimetrazine tartrate should not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter preparations and herbal products.

In a case-control epidemiological study, the use of anorectic agents, including phendimetrazine tartrate, was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder. The use of anorectic agents for longer than three months was associated with a 23-fold increase in the risk of developing pulmonary hypertension. Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded.

The onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema suggest the possibility of occurrence of pulmonary hypertension. Under these circumstances, phendimetrazine tartrate should be immediately discontinued, and the patient should be evaluated for the possible presence of pulmonary hypertension.

Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported. Possible contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. However, no cases of this valvulopathy have been reported when phendimetrazine tartrate has been used alone.

The potential risk of possible serious adverse effects such as valvular heart disease and pulmonary hypertension should be assessed carefully against the potential benefit of weight loss. Baseline cardiac evaluation should be considered to detect pre-existing valvular heart diseases or pulmonary hypertension prior to initiation of phendimetrazine treatment. Phendimetrazine tartrate is not recommended in patients with known heart murmur or valvular heart disease. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur. To limit unwarranted exposure and risks, treatment with phendimetrazine tartrate should be continued only if the patient has satisfactory weight loss within the first 4 weeks of treatment (i.e., weight loss of at least 4 pounds, or as determined by the physician and patient).

Tolerance to the anorectic effect of phendimetrazine develops within a few weeks. When this occurs, its use should be discontinued; the maximum recommended dose should not be exceeded.

Use of phendimetrazine tartrate within 14 days following the administration of monoamine oxidase inhibitors may result in a hypertensive crisis.

Abrupt cessation of administration following prolonged high dosage results in extreme fatigue and depression. Because of the effect on the central nervous system, phendimetrazine tartrate 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.

Phendimetrazine tartrate is not recommended for patients who used any anorectic agents within the prior year.

PRECAUTIONS

Caution is to be exercised in prescribing phendimetrazine for patients with even mild hypertension.

Insulin requirements in diabetes mellitus may be altered in association with the use of phendimetrazine tartrate and the concomitant dietary regimen.

Phendimetrazine tartrate may decrease the hypotensive effect of guanethidine. The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Drug Interactions

Efficacy of phendimetrazine tartrate with other anorectic agents has not been studied and the combined use may have the potential for serious cardiac problems.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with phendimetrazine tartrate have not been performed to evaluate carcinogenesic potential, mutagenesic potential or effects on fertility.

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with phendimetrazine tartrate. It is also not known whether phendimetrazine tartrate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Usage in Pregnancy

Safe use in pregnancy has not been established. Until more information is available, phendimetrazine tartrate should not be taken by women who are or may become pregnant unless, in the opinion of the physician, the potential benefits outweigh the possible hazards.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, phendimetrazine tartrate should not be taken by women who are nursing unless, in the opinion of the physician, the potential benefits outweigh the possible hazards.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS

Cardiovascular: Palpitation, tachycardia, elevated blood pressure, ischemic events.

Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine, both independently and especially when used in combination with other anorectic drugs, have been reported. However, no case of this valvulopathy have been reported when phendimetrazine tartrate has been used alone.

Central Nervous System: Overstimulation, restlessness, insomnia, agitation, flushing, tremor, sweating, dizziness, headache, psychotic state, blurring of vision.

Gastrointestinal: Dryness of the mouth, nausea, diarrhea, constipation, stomach pain.

Genitourinary: Urinary frequency, dysuria, changes in libido.

DRUG ABUSE AND DEPENDENCE

Controlled Substance

Phendimetrazine tartrate tablets are a Schedule III controlled substance.

Dependence

Phendimetrazine tartrate is related chemically and pharmacologically to the amphetamines. Amphetamines and related stimulant drugs have been extensively abused, and the possibility of abuse of phendimetrazine 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 to many times that 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. The most severe manifestation of chronic intoxications is psychosis, often clinically indistinguishable from schizophrenia.

OVERDOSAGE

Acute overdosage with phendimetrazine tartrate may manifest itself by the following signs and symptoms: unusual restlessness, confusion, belligerence, hallucinations, and panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Poisoning may result in convulsions, coma, and death.

The management of overdosage is largely symptomatic. It includes sedation with a barbiturate. If hypertension is marked, the use of a nitrate or rapid-acting alpha receptor-blocking agent should be considered. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations for its use.

DOSAGE AND ADMINISTRATION

Usual Adult Dosage: 1 tablet (35 mg) twice a day or three times a day one hour before meals.

Dosage should be individualized to obtain an adequate response with the lowest effective dosage. In some cases, 1/2 tablet (17.5 mg) per dose may be adequate. Dosage should not exceed 2 tablets three times a day.

HOW SUPPLIED

Each white, round tablet contains 35 mg phendimetrazine tartrate, and is debossed "X" on one side and "3" score "5" on the other side. Tablets are supplied:

NDC 12634-028-00 Bottles of 10

NDC 12634-028-01 Bottles of 100

NDC 12634-028-09 Bottles of 35

NDC 12634-028-40 Bottles of 40

NDC 12634-028-42 Bottles of 42

NDC 12634-028-45 Bottles of 45

NDC 12634-028-50 Bottles of 50

NDC 12634-028-52 Blister Pack of 12

NDC 12634-028-54 Blister Pack of 14

NDC 12634-028-57 Blister Pack of 20

NDC 12634-028-58 Blister Pack of 28

NDC 12634-028-59 Blister Pack of 30

NDC 12634-028-60 Bottles of 60

NDC 12634-028-61 Blister Pack of 10

NDC 12634-028-63 Blister Pack of 3

NDC 12634-028-66 Blister Pack of 6

NDC 12634-028-67 Blister Pack of 7

NDC 12634-028-69 Blister Pack of 9

NDC 12634-028-71 Bottles of 30

NDC 12634-028-74 Bottles of 24

NDC 12634-028-78 Bottles of 28

NDC 12634-028-79 Bottles of 25

NDC 12634-028-80 Bottles of 20

NDC 12634-028-81 Bottles of 21

NDC 12634-028-82 Bottles of 12

NDC 12634-028-84 Bottles of 14

NDC 12634-028-85 Bottles of 15

NDC 12634-028-90 Bottles of 90

NDC 12634-028-91 Blister Pack of 1

NDC 12634-028-92 Bottles of 2

NDC 12634-028-93 Bottles of 3

NDC 12634-028-94 Bottles of 4

NDC 12634-028-95 Bottles of 5

NDC 12634-028-96 Bottles of 6

NDC 12634-028-97 Bottles of 7

NDC 12634-028-98 Bottles of 8

NDC 12634-028-99 Bottles of 9

STORAGE

Store at 20ºC to 25ºC (68º to 77ºF); [see USP Controlled Room Temperature].

Dispense in tight containers with child-resistant closures.

Rx only

Manufactured by

Mikart, Inc.

Atlanta, GA 30318

Code 842Z00

Rev. 09/12

Repackaged and Distributed by:

Apotheca Inc.

Phoenix, AZ 85006

PRINICIPAL DISPLAY PANEL

label

PHENDIMETRAZINE TARTRATE 
phendimetrazine tartrate tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:12634-028(NDC:46672-174)
Route of AdministrationORALDEA ScheduleCIII    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
PHENDIMETRAZINE TARTRATE (UNII: 6985IP0T80) (PHENDIMETRAZINE - UNII:AB2794W8KV) PHENDIMETRAZINE TARTRATE35 mg
Inactive Ingredients
Ingredient NameStrength
CALCIUM PHOSPHATE, DIBASIC, DIHYDRATE (UNII: O7TSZ97GEP)  
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
Product Characteristics
Colorwhite, whiteScore2 pieces
ShapeROUNDSize8mm
FlavorImprint Code 3;5;X
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:12634-028-0010 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
2NDC:12634-028-01100 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
3NDC:12634-028-0935 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
4NDC:12634-028-4040 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
5NDC:12634-028-4242 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
6NDC:12634-028-4545 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
7NDC:12634-028-5050 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
8NDC:12634-028-5212 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
9NDC:12634-028-5414 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
10NDC:12634-028-5720 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
11NDC:12634-028-5828 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
12NDC:12634-028-5930 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
13NDC:12634-028-6060 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
14NDC:12634-028-6110 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
15NDC:12634-028-633 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
16NDC:12634-028-666 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
17NDC:12634-028-677 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
18NDC:12634-028-699 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
19NDC:12634-028-7130 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
20NDC:12634-028-7424 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
21NDC:12634-028-7828 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
22NDC:12634-028-7925 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
23NDC:12634-028-8020 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
24NDC:12634-028-8121 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
25NDC:12634-028-8212 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
26NDC:12634-028-8414 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
27NDC:12634-028-8515 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
28NDC:12634-028-9090 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
29NDC:12634-028-911 in 1 BLISTER PACK; Type 0: Not a Combination Product06/27/2000
30NDC:12634-028-922 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
31NDC:12634-028-933 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
32NDC:12634-028-944 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
33NDC:12634-028-955 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
34NDC:12634-028-966 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
35NDC:12634-028-977 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
36NDC:12634-028-988 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
37NDC:12634-028-999 in 1 BOTTLE; Type 0: Not a Combination Product06/27/2000
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA08945206/27/2000
Labeler - Apotheca Inc. (051457844)
Establishment
NameAddressID/FEIBusiness Operations
Apotheca Inc.051457844relabel(12634-028) , repack(12634-028)

Revised: 7/2016
Document Id: 375fdeb5-e1ca-1a8e-e054-00144ff8d46c
Set id: b045cbd6-68ca-4a9b-a6e6-625d736a079b
Version: 4
Effective Time: 20160711
 
Apotheca Inc.