OBESAN X

Indications

• Obesity management
• Weight loss in conjunction with a reduced-calorie diet

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in the paediatric population.

Adults: Refer to the BNF for specific dosing recommendations. Generally, phendimetrazine is administered in a dosage that facilitates weight loss, typically part of a comprehensive weight management program.

Mechanism of action

Phendimetrazine may act similarly to amphetamines by activating the alpha-adrenergic system, leading to appetite suppression and increased metabolic activity. It functions as a norepinephrine-dopamine releasing agent (NDRA) and can reverse the norepinephrine transporter (NET). The active metabolite phenmetrazine exhibits potent activity in releasing norepinephrine and dopamine, contributing to its appetite-suppressing effects.

Pharmacodynamics

Phendimetrazine, being a phenylalkylamine sympathomimetic amine, demonstrates central nervous system stimulation and an increase in blood pressure. It is classified as an anorectic or anorexigenic drug, suggesting its primary use in the treatment of obesity may involve appetite suppression. However, other central nervous system actions and metabolic effects might also play a role in its efficacy. Tolerance and tachyphylaxis have been noted with the use of drugs in this class.

Pharmacokinetics

Phendimetrazine is absorbed and metabolized in the body, with the active metabolite phenmetrazine responsible for its therapeutic effects. The pharmacokinetic profile includes a variable half-life, influenced by individual metabolic rates. Detailed pharmacokinetic parameters such as volume of distribution and clearance rates are not extensively documented, highlighting a need for further research.

Contra-indications

• Hypersensitivity to phendimetrazine or any of its components
• Severe hypertension
• Cardiovascular disease
• Hyperthyroidism
• History of drug abuse
• Glaucoma

Adverse effects

• Increased heart rate
• Insomnia
• Dry mouth
• Nervousness
• Dizziness
• Headache
• Gastrointestinal disturbances

Interactions

• MAO inhibitors may lead to hypertensive crisis when taken with phendimetrazine
• Other central nervous system stimulants may enhance adverse effects
• Antihypertensive agents may have reduced effectiveness

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor blood pressure regularly during treatment
• Assess for signs of tolerance and dependence
• Consider the potential for increased heart rate and blood pressure

Pregnancy

Phendimetrazine is classified as a Category C drug. Risk cannot be ruled out. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if phendimetrazine is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 35 mg

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. Phendimetrazine is an effective and widely prescribed appetite suppressant. Preclinical findings show that phendimetrazine displays stimulant properties similar to amphetamine, but few studies have examined the neurochemical mechanism of the drug. ... Phendimetrazine itself had no effect on uptake or release of any transmitter. In contrast, the trans-configured N-demethylated metabolite, phenmetrazine, was a potent releaser of [3H]norepinephrine (EC(50)=50 nM) and [3H]dopamine (EC(50)=131 nM). The cis N-demethylated metabolite, pseudophenmetrazine, displayed modest potency at releasing [3H]norepinephrine (EC(50)=514 nM) and blocking [3H]dopamine re-uptake (IC(50)=2630 nM). All drugs tested were inactive or weak in the [3H]5-HT assays. When injected intravenously, phendimetrazine had minimal effects on extracellular transmitter levels, whereas phenmetrazine produced dose-related elevations in extracellular dopamine. The collective findings suggest that phendimetrazine is a "prodrug" that is converted to the active metabolite phenmetrazine, a potent substrate for norepinephrine and dopamine transporters.

Pharmacodynamics

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.