Affecting Nutrition and Metabolism
= Additional active ingredients
Phentermin (as resinate) 15 mg.
PRESENTATION AND DOSSAGE
CAPS: 30 X 15 mg (Sustained Action)
For the treatment of severe obesity that has not responded to an appropriate diet- a minimal body mass index of 30 kg/m² is required.
Known hypersensitivity or idiosyncrasy to sympathomimetic amines or to any of its excipients.
Pulmonary artery hypertension, Existing heart valve abnormalities or heart murmurs, Moderate to severe arterial hypertension, Cerebrovascular disease, Severe cardiac disease including arrhythmias, Advanced arteriosclerosis, Hyperthyroidism, Agitated states or a history of psychiatric illness 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 administratio, Pregnancy and breast-feeding wome, Co-administration of drug products for weight loss.
Razin capsules are indicated only as short-term monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with phentermine and other drug products for weight loss, including selective serotonin reuptake inhibitors, have not been established. Therefore, the coadministration of these drug products for weight loss is not recommended. 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 phentermine alone cannot be ruled out. The initial symptom of PPH is usually dyspnea. Other initial symptoms 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 patient who develop new, unexplained symptoms of dyspnea, angina pectoris, syncope, or lower extremity edema.
Valvular Heart Disease: Serious regurgitant 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 phentermine with fenfluramine or dexfenfluramine for weight loss. The etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. If tolerance to the “anorectic” effect develops, the recommended dose should not be exceeded in an attempt to increase the effect: rather, the drug should be discontinued. Razin 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. When using CNS active agents, consideration must always be given to the possibility of adverse interactions with alcohol.
Drug Dependence: Razin is related chemically and pharmacologically to amphetamine (d- and dl-amphetamine) and other stimulant drugs that have been extensively abused. The possibility of abuse of Razin should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. Abuse of amphetamine (d- and dl-amphetamine) 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 some 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. The most severe manifestation of chronic intoxications is psychosis, often clinically indistinguishable from schizophrenia.
Pediatric Use: Razin Capsules (phentermine resin) are not recommended for use in pediatric patients under 16 years old. Caution is to be exercised in prescribing Razin for patients with even mild hypertension. Insulin requirements in diabetes mellitus may be altered in association with the use of Razin and the concomitant dietary regimen. Razin may decrease the hypotensive effect of adrenergic neuron blocking drugs. The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage. Rarely, cases of cardiac and cerebrovascular accidents have been reported, often following rapid weight loss. Special care should be taken to ensure gradual and controlled weight loss in obese patients, who have an increased risk of vascular disease. Razin should be used with caution in patients under treatment with anti-hypertensive agents, since it may cause some loss of blood pressure control, and in patients receiving psychotropic drugs, including sedatives and sympathomimetic agents. Razin should be used with caution in epileptic patients. Inappropriate use of Razin and similar medicines has been reported and the possibility of this occurrence should be considered and patients managed accordingly. As a result patients should be reviewed regularly in the process of their treatment and informed of other measures to effect weight loss. Razin should not be used in men or women for loss of weight for cosmetic reasons. Those who have failed to respond to medical treatment for weight loss in the past should only be treated after review by a medical practitioner specialising in the treatment of weight loss. The ability of the patient to maintain effective lifestyle interventions of exercise and diet, and adhere to a medical regimen should be assessed before treatment is commenced.
Geriatric Use: Clinical studies of phentermine did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Cardiovascular: Primary pulmonary hypertension, palpitation, tachycardia, levation of blood pressure and precordial pain. Rarely, cases of cardiovascular or cerebrovascular accidents have been described in patients treated with anorectic agents. In particular stroke, angina, myocardial infraction, cardiac failure and cardiac arrest have been reported.
Central Nervous System: Overstimulation, restlessness, nervousness, dizziness, headache, insomnia, euphoria may occur and this may be followed by fatigue and depression, dysphoria, tremor, headache; rarely psychotic episodes and hallucinations at recommended doses with some drugs in this class.
Gastrointestinal: Dryness of the mouth, abdominal cramps, unpleasant taste, diarrhea, constipation, nausea, vomiting, other gastrointestinal disturbances.
Allergic Reaction: Urticaria, rash, facial edema.
Endocrine Effects: Impotence, changes in libido.
Other: Micturition disturbances.
Use Razin with caution in patients receiving sympathomimetic agents. Response to insulin and oral hypoglycaemic agents may vary in patients receiving phentermine. Phentermine antagonises adrenergic neurone blocking drugs such as clonidine, methyldopa and guanethidine and may decrease their hypotensive effect. The effects of phentermine are potentiated by monoamine oxidase inhibitors (see contraindications) and may result in a hypertensive crisis. The concurrent use of thyroid hormones with Razin may increase the CNS stimulation that can occur with Razin. Alcohol may increase CNS side effects such as dizziness, light-headedness and confusion and its concurrent use should be avoided with Razin. Serotonin reuptake inhibitors and tricyclic antidepressants may interact with Razin by increasing serotonin levels, and Razin should be used with caution in those taking these agents. Since the selective serotonin reuptake inhibitors (eg fluoxetine, sertraline, fluvoxamine, paroxetine), ergot derived drugs and clomipramine affect serotonin metabolism there remains a theoretical risk that combination of these agents with phentermine may also be associated with cardiac valvular disease, although there is no direct scientific evidence to confirm this theory. In a single-dose study comparing the exposures after oral administration of a combination capsule of 15 mg phentermine and 92 mg topiramate to the exposures after oral administration of a 15 mg phentermine capsule or a 92 mg topiramate capsule, there is no significant topiramate exposure change in the presence of phentermine. However in the presence of topiramate, phentermine Cmax and AUC increase 13% and 42% respectively.
Adults and children aged over 16 years: One capsule daily at breakfast, swallowed whole.
Symptoms and signs: Manifestations of acute overdosage may include euphoria, irritability, restlessness, tremor, hyperreflexia, rapid respiration, confusion, agitation, assaultiveness, disorientation hallucinations,
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. Overdosage of pharmacologically similar compounds has resulted in fatal poisoning, usually terminating in convulsions and coma.
Treatment: The treatment of overdose is largely symptomatic. However, the stomach should be emptied by
gastric lavage and washed out with water if the preparation has been ingested within the last three or four hours. Gastric lavage, followed by activated charcoal, may be the optimal decontamination regimen for patient expressing CNS depression. Diazepam, preferably by mouth (cautiously by intravenous injection) can be used to control marked excitement and convulsions. Sedation with a barbiturate can be considered. Provided renal function is adequate, acidification of the urine has been shown to increase elimination of phentermine. There is insufficient experience to recommend haemodialysis or peritoneal dialysis. Intravenous phentolamine (Regitine) has been suggested on pharmacologic grounds for possible acute, severe hypertension, if this complicates overdosage.
PREGNANCY & LACTATION
Pregnancy: Studies in animal have shown evidence of an increase occurrence of fetal damage, the significance of which is considered uncertain in humans. Due to inadequate evidence of safety in
human pregnancy, Razin is contraindicated in pregnant women.
Lactation: There is no data available on the safety of Razin in lactation and such as, its use in lactating women is contraindicated.
MANUFACTURER & DISTRIBUTER:
Manufacturer: CTS Chemical Ind. Ltd.
License Holder: CTS Chemical Ind. Ltd.