DUROMINE 30

Indications

• Obesity management
• Short-term weight loss in conjunction with diet and exercise

Dosage

Adults: The usual adult dose is 15-37.5 mg taken once daily, typically in the morning, 30 minutes before breakfast or 1-2 hours after breakfast.

Mechanism of action

Phentermine acts by releasing noradrenaline from presynaptic vesicles in the lateral hypothalamus, stimulating beta2-adrenergic receptors. This leads to increased levels of norepinephrine and dopamine, which suppress appetite. Additionally, it may inhibit neuropeptide Y, a key hunger signal, contributing to its appetite-suppressing effects. Although it is a weak inhibitor of monoamine oxidase, this mechanism is not clinically significant.

Pharmacodynamics

Phentermine primarily induces appetite suppression, potentially through increased leptin levels and other mechanisms. Clinical studies have indicated that phentermine can result in an average weight loss of 3.6 kg over a period of 2-24 weeks compared to placebo. It has also been noted for helping patients maintain weight loss after discontinuation. Unlike amphetamines, phentermine does not typically produce significant central nervous system side effects, nor does it lead to tachyphylaxis or prolongation of the QT interval.

Pharmacokinetics

Phentermine is absorbed rapidly after oral administration, with peak plasma concentrations occurring within 3.5 to 4.5 hours. It is primarily metabolized in the liver, and its elimination half-life is approximately 20 hours. The drug is excreted mainly in urine as unchanged drug and metabolites. Due to its pharmacokinetic profile, adjustments may be necessary in patients with hepatic impairment.

Contra-indications

• Hypersensitivity to phentermine or any of its excipients
• Hyperthyroidism
• Severe cardiovascular disease
• Pulmonary hypertension
• History of drug abuse
• Glaucoma
• Pregnancy

Adverse effects

• Insomnia
• Dry mouth
• Constipation
• Increased heart rate
• Elevated blood pressure
• Dizziness
• Nervousness
• Headache

Interactions

• Monoamine oxidase inhibitors (MAOIs) - may cause hypertensive crisis
• Other sympathomimetics - may enhance cardiovascular effects
• Antihypertensive agents - may reduce effectiveness
• Serotonergic drugs - increased risk of serotonin syndrome

Precautions

• Monitor for signs of cardiovascular complications
• Use with caution in patients with a history of substance abuse
• Assess for potential interactions with other medications
• Monitor blood pressure and heart rate regularly

Pregnancy

Phentermine is contraindicated in pregnancy due to potential risks to the fetus.

Breast-feeding

It is not known whether phentermine is excreted in human milk; caution is advised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral tablets
• Oral capsules

Mechanism of action

Phentermine is an indirect-acting sympathomimetic agent that acts by releasing noradrenaline from the presynaptic vesicles in the lateral hypothalamus. This increase in noradrenaline concentration in the synaptic cleft results in the stimulation of beta2-adrenergic receptors. Phentermine is classified as an indirect sympathomimetic due to the increase in the level of norepinephrine, dopamine and its indirect effect towards serotonin. Some reports have indicated that phentermine inhibits the neuropeptide Y which is a principal signaling pathway for the induction of hunger. This combined effect produces a continuous flight-or-fight response in the body which reduces the hunger signal as this state is on the immediate need for energy. Lastly, some reports have indicated that phentermine is a weak inhibitor of monoamine oxidase but this mechanism does not tend to produce a clinically significant response. Although the mechanism of action of the sympathomimetic appetite suppressants in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Amphetamine and related sympathomimetic medications ... are thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite. ... It has not been established that the actions of these medications in treating obesity is primarily suppression of appetite; other CNS actions and/or metabolic effects, such as decreased gastric acid secretion or increased energy expenditure, may be involved.

Pharmacodynamics

It is reported that the main mechanism of action of phentermine is the generation of appetite suppression, maybe due to the increase in leptin, but it is considered that other mechanisms should be involved. Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure. In clinical studies where phentermine was used as a monotherapy and as combination therapy, this drug has shown an average weight loss of 3.6 kg when compared with the placebo in 2-24 weeks. Patients treated with phentermine also showed increased maintenance of the weight after treatment discontinuation. As well, even though it is a derivative of the amphetamines, it has not been registered to produce any of the effects of amphetamine such as central nervous system stimulation, elevation of blood pressure, tachyphylaxis or QTc prolongation.