Phentermine has some similarity in its pharmacodynamics with its parent compound, amphetamine, as they both are TAAR1 agonists, where the activation of TAAR1 in monoamine neurons facilitates the efflux or, release into the synapse, of these neurochemicals; at clinically relevant doses, phentermine primarily acts as a releasing agent of norepinephrine in neurons, although, to a lesser extent, it releases dopamine and serotonin into synapses as well. Phentermine may also trigger the release of monoamines from VMAT2, which is a common pharmacodynamic effect among substituted amphetamines. The primary mechanism of phentermine's action in treating obesity is the reduction of hunger perception, which is a cognitive process mediated primarily through several nuclei within the hypothalamus (in particular, the lateral hypothalamic nucleus, arcuate nucleus, and ventromedial nucleus). Outside the brain, phentermine releases norepinephrine and epinephrine – also known as noradrenaline and adrenaline respectively – causing fat cells to break down stored fat as well.
Phentermine is used for a short period of time to promote weight loss, if exercise and calorie reduction are not sufficient, and in addition to exercise and calorie reduction.
Phentermine is approved for up to 12 weeks of use and most weight loss occurs in the first weeks. However, significant loss continues through the sixth month and has been shown to continue at a slower rate through the ninth month.
The following adverse reactions to phentermine have been identified:
Primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevation of blood pressure, ischemic events.
Central Nervous System
Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, psychosis.
Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances.
Impotence, changes in libido.
Dosage should be individualized to obtain an adequate response with the lowest effective dose.
The usual adult dose is one capsule (37.5 mg) daily as prescribed by the physician, administered before breakfast or 1 to 2 hours after breakfast for appetite control.
The usual adult dose is one tablet (37.5 mg) daily as prescribed by the physician, administered before breakfast or 1 to 2 hours after breakfast. The dosage may be adjusted to the patient’s need. For some patients, half tablet (18.75 mg) daily may be adequate, while in some cases it may be desirable to give half tablets (18.75 mg) two times a day.
ADIPEX-P® is not recommended for use in pediatric patients less than or equal to 16 years of age.
Late evening medication should be avoided because of the possibility of resulting insomnia.
Dosage In Patients With Renal Impairment
The recommended maximum dosage of ADIPEX-P® is 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2 ). Avoid use of ADIPEX-P®in patients with eGFR less than 15 mL/min/1.73 m2 or end-stage renal disease requiring dialysis.
Monoamine Oxidase Inhibitors
Use of ADIPEX-P® is contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors because of the risk of hypertensive crisis.
Concomitant use of alcohol with ADIPEX-P® may result in an adverse drug reaction.
Insulin And Oral Hypoglycemic Medications
Requirements may be altered
Adrenergic Neuron Blocking Drugs
ADIPEX-P® may decrease the hypotensive effect of adrenergic neuron blocking drugs.
Phentermine is a Schedule IV controlled substance.
Phentermine is related chemically and pharmacologically to the amphetamines. Amphetamines and other stimulant drugs have been extensively abused and the possibility of abuse of phentermine 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 of these drugs 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. A severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.
Adipex-P® is best stored at room temperature away from direct light and moisture. To prevent drug damage, you should not store Adipex-P® in the bathroom or the freezer. There may be different brands of Adipex-P® that may have different storage needs. It is important to always check the product package for instructions on storage, or ask your pharmacist. For safety, you should keep all medicines away from children and pets.
ADIPEX-P® is indicated only as short-term (a few weeks ) monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with ADIPEX-P® and any other drug products for weight loss including prescribed drugs, over-the-counter preparations, and herbal products, or serotonergic agents such as selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established. Therefore, coadministration of ADIPEX-P® and these drug products is not recommended.
Primary Pulmonary Hypertension
Primary Pulmonary Hypertension (PPH) – a rare, frequently fatal disease of the lungs – has been reported to occur in patients receiving a combination of phentermine with fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of ADIPEX-P® alone cannot be ruled out; there have been rare cases of PPH in patients who reportedly have taken phentermine alone. The initial symptom of PPH is usually dyspnea. Other initial symptoms may include angina pectoris, syncope or lower extremity edema. Patients should be advised to report immediately any deterioration in exercise tolerance. Treatment should be discontinued in patients who develop new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema, and patients should be evaluated for the possible presence of pulmonary hypertension.
Valvular Heart Disease
Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricus pid valves, has been reported in otherwise healthy persons who had taken a combination of phentermine with fenfluramine or dexfenfluramine for weight loss. The possible role of phentermine in the etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. The possibility of an association between valvular heart disease and the use of ADIPEX-P® alone cannot be ruled out; there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone.
Development Of Tolerance, Discontinuation In Case Of Tolerance
When tolerance to the anorectant effect develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.
Effect On The Ability To Engage In Potentially Hazardous Tasks
ADIPEX-P® 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.