indication

Used in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.

pharmacology

Phendimetrazine is a phenylalkylamine 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 has 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.

mechanism of action

Phendimetrazine may act in a similar way to amphetamines in that it activates the alpha-adrenergic system to induce an appetite suppressive and metabolic increase effect. The drug also acts as a norepinephrine-dopamine releasing agent (NDRA). It can bind to and reverse the NET.

toxicity

Acute overdosage of phendimetrazine may manifest itself by the following signs and symptoms: unusual restlessness, confusion, belligerance, 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.

biotransformation

Approximately 30% of a given dose of phendimetrazine is metabolized into phenmetrazine, which may account for part of its anorectic effect, and probably also influences abuse potential; individuals who metabolise a greater proportion of phendimetrazine into phenmetrazine are more likely to develop problems with dependence and addiction

absorption

Peak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours.

half life

19-24 hours

route of elimination

The major route of elimination is via the kidneys where most of the drug and metabolites are excreted.

drug interactions

Chlorpromazine: Decreased anorexic effect, may increases psychotic symptoms

Fluoxetine: Risk of serotoninergic syndrome

Fluphenazine: Decreased anorexic effect, may increase psychotic symptoms

Fluvoxamine: Risk of serotoninergic syndrome

Guanethidine: Phendimetrazine may decrease the effect of guanethidine.

Isocarboxazid: Possible hypertensive crisis

Mesoridazine: Decreased anorexic effect, may increase psychotic symptoms

Methotrimeprazine: Decreased anorexic effect, may increase psychotic symptoms

Paroxetine: Risk of serotoninergic syndrome

Perphenazine: Decreased anorexic effect, may increase psychotic symptoms

Phenelzine: Possible hypertensive crisis

Prochlorperazine: Decreased anorexic effect, may increase pyschotic symptoms

Promethazine: Decreased anorexic effect, may increase pyschotic symptoms

Propericiazine: Decreased anorexic effect, may increase pyschotic symptoms

Rasagiline: Possible hypertensive crisis

Thioridazine: Decreased anorexic effect, may increase psychotic symptoms

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trandolapril: Phendimetrazine may reduce the efficacy of Trandolapril.

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Phendimetrazine. Concomitant therapy should be avoided.

Trifluoperazine: Decreased anorexic effect, may increase psychotic symptoms

Triprolidine: Triprolidine may reduce the sedative effect of the antihistamine, Phendimetrazine.