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Duromine
Phentermine
NAME OF THE DRUG
Phentermine (phenyl tertiary
butylamine, C10H15N)
DESCRIPTION
Each Duromine capsule contains phentermine as an ion-exchange resin complex
equivalent to 15 or 30 mg phentermine depending on strength. The
ion-exchange resin is quite stable, highly insoluble and without
pharmacological effect until it reacts with cations (hydrogen, potassium,
sodium etc) present in the gastrointestinal fluids. Phentermine is then
released from the resin complex at a rate dependent on the total
concentration of these cations. Since this concentration is fairly constant
throughout the entire gastrointestinal tract, continuous and controlled
ionic release occurs over a 10 to 14 hour period.
PHARMACOLOGY
Pharmacodynamic properties
Phentermine is a sympathomimetic amine with significant anorectic activity
in animal models. Its appetite suppressant effect is generally considered to
be exerted through the hypothalamus, but it is not certain that this is the
only effect related to weight loss. Phentermine has major effects on the
dopaminergic and noradrenergic nervous systems. The cardiovascular effects
include a pressor response and increase in heart rate and force of
contraction.
Pharmacokinetic properties
Absorption of phentermine is almost complete. The rate of absorption from
the resin complex is significantly slower than that from the hydrochloride
salt resulting in a lower and later peak blood level. Phentermine is readily
absorbed from the gastro-intestinal tract. Following an oral dose of
phentermine capsule, one study demonstrated urinary excretion of unchanged
drug ranging from 62.7% to 84.8% in 72 hours. The remainder is metabolised
in the liver. The half-life of phentermine is about 25 hours. In one study
in volunteers acidification of the urine reduced the half-life to 7 - 8
hours.
INDICATIONS
Duromine is an anorectic agent indicated in the management of obesity
as a short-term adjunct in a medically monitored comprehensive regimen of
weight reduction based, for example, on exercise, diet (caloric/kilojoule
restriction) and behaviour modification in obese patients with a body mass
index (BMI) of 30 kg/m2 or greater. The treatment with Duromine
can be initiated in overweight patients with a lower BMI (25 to 29.9 kg/m2)
which increases the risk of morbidity from a number of disorders. Secondary
organic causes of obesity should be excluded by diagnosis before prescribing
this agent.
CONTRAINDICATIONS
Pulmonary artery hypertension; existing heart valve abnormalities or heart
murmurs; moderate to severe arterial hypertension; cerebra-vascular disease;
severe cardiac disease including arrhythmias, advanced arteriosclerosis;
known hypersensitivity to sympathomimetic drugs; hyperthyroidism; agitated
states or a history of psychiatric illnesses including anorexia nervosa and
depression; glaucoma; history of drug/alcohol abuse or dependence;
concomitant treatment with Monoamine Oxidase (MAO) Inhibitors or within 14
days following their administration.
PRECAUTIONS
Special Precautions
Duromine capsules are indicated only as short-term monotherapy for the
management of exogenous obesity. The safety and efficacy of combination
therapy with phentermine and any other drug products for weight loss have
not been established. Therefore, coadministration of drug products for
weight loss is not recommended.
Since the selective serotonin reuptake inhibitors (e.g., fluoxetine,
sertraline, paroxetine), ergot-like drugs and clomipramine affect serotonin
disposition there remains a theoretical risk that combination of these
agents with phentermine may also be associated with cardiac valvular disease
and is not recommended. There is no direct scientific evidence to confirm
this theory.
Valvular Heart
Disease: Serious regurgitate cardiac valvular disease, primarily
affecting the mitral, aortic and/or tricuspid valves, has been reported in
otherwise healthy persons who had taken a combination of fenfluramine or
dexfenfluramine with phentermine for weight loss. The aetiology of these
valvulopathies has not been established and their course in individuals
after the drugs are stopped is not known. There have been no reported cases
to date of valvular heart disease occurring with the use of phentermine
alone.
Primary Pulmonary Hypertension (PPH): Cases of severe,
sometime fatal primary pulmonary hypertension, have been reported in
patients who have received anorectics. In a case-control epidemiological
study, the duration of treatment with anorectic agents, not including
phentermine, beyond three months significantly increases the risk of PPH.
However, patients treated with phentermine require medical review at least
every 3 months (Refer to "Dosage and Administration"). PPH has been reported
in patients receiving fenfluramine/dexfenfluramine combined with phentermine.
The possibility of an association between PPH and the use of phentermine
alone cannot be ruled out; there have been very rare cases of PPH in
patients who reportedly have taken phentermine alone. The initial symptom of
PPH is usually dyspnoea. Other early symptoms include: angina pectoris,
syncope, lower extremity oedema or the unexplained onset or aggravation of
diminished exercise tolerance. Under these circumstances, treatment should
be immediately discontinued and the patient referred to a specialist unit
for investigation.
Use with caution in the following circumstances
Duromine should be used with caution in patients with mild hypertension. In
the first days of treatment, determine that there is no loss of blood
pressure control. In patients receiving Duromine, response to insulin and
oral hypoglycaemic agents may vary due to alterations in dietary regimes.
This should be kept in mind if Duromine is used in diabetic patients.
Duromine may impair the ability to perform activities requiring mental
alertness, such as driving and operating machinery, and patients therefore
should be cautioned accordingly. Inappropriate use has been reported with
similar drugs and the possibility of this occurrence should be considered
with Duromine.
Cardiovascular and
cerebrovascular events have rarely been reported, mainly in association with
rapid weight loss. Weight loss should be gradual and controlled in obese
patients undergoing treatment with Duromine. Duromine should be used with
caution in patients with established coronary artery disease. A single case
of exacerbation of angina pectoris in a patient with established coronary
artery disease has been reported. Duromine should be used with caution in
patients receiving psychotrophic drugs, including sedatives and agents with
sympathomimetic activity. Duromine should be used with caution in epileptic
patients. Duromine should be used with caution in patients receiving
anti-hypertensive agents.
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