General Information: Phendimetrazine is an oral, indirect-acting, nonamphetamine sympathomimetic amine. It is used as an anoretic agent for short-term (8 to 12 weeks) adjunct in the treatment of exogenous obesity. The pharmacologic effects of phendimetrazine are similar to amphetamines. Phendimetrazine is only indicated for use as monotherapy. This drug was approved by the FDA in 1961.
Phendimetrazine tartrate is a weight loss medication, which is chemically related to amphetamines and is commonly prescribed for the treatment of obesity. Essentially an appetite suppressant, phendimetrazine tartrate is categorized as a Schedule III drug under the Convention on Psychotropic Substances and the Uniform Controlled Substances Act of 1970.
After being developed in Germany in 1954, phendimetrazine tartrate was quickly recognized for its efficacy and potential benefits. By the 1960s it had met the approval criteria of the United States Food and Drug Administration (FDA), passing its safety and effectiveness tests as an approved formula for weight loss and in the mid-90s its popularity increased after the FDA banned the diet drug Ephedra for its dangerous and potentially fatal side effects.
The latest diet pill rankings list phendimetrazine tartrate as the second most popular appetite suppressant formula in America and it is considered to be an effective and safe weight control aid when taken as directed.
Mechanism of Action: Similar to amphetamines, phendimetrazine increases the release of norepinephrine and dopamine from nerve terminals and inhibits their reuptake. Clinical effects include CNS stimulation and elevation of blood pressure. Appetite suppression is believed to occur through direct stimulation of the satiety center in the hypothalamic and limbic region.
Tolerance to the anorexiant effects of phendimetrazine usually develops within a few weeks of starting therapy. The mechanism of tolerance appears to be pharmacodynamic in nature; higher doses of phendimetrazine are required to produce the same response. When tolerance develops to the anorexiant effects, it is generally recommended that phendimetrazine be discontinued rather than the dose increased.
Pharmacokinetics: Once in systemic circulation, some of the drug is metabolized to phenmetrazine and phendimetrazine-N-oxide. The main route of elimination for unchanged drug and metabolites is the kidneys and the average elimination half-life for regular-release forms is about 1.9 hours or 9.8 hours for sustained-release forms.
Oral Route: Phendimetrazine is readily absorbed from the gastrointestinal tract. The absorption half-life is approximately the same for both regular-release and sustained-release formulations. This indicates a similar onset of action between sustained-release and regular-release dosage forms. The duration of action for regular-release forms is about 4 hours; the duration is prolonged for sustained-release formulations.
Indications: Phendimetrazine tartrate is indicated as a short-term supplement to diet and exercise in the treatment of obesity. However, the appetite suppressing action of such drugs in the treatment of obesity is only considered to be primary as other central nervous system actions or metabolic effects may also be involved. For example, phendimetrazine tartrate may act in a similar way to amphetamines in that it activates the alpha-adrenergic system to induce both appetite suppressive and metabolic elevating effects. Furthermore, it also seems to act as a norepinephrine-dopamine releasing agent (NDRA).
Contraindications/Precautions: Who should not take this medication? Do not take phendimetrazine if you are pregnant or trying to become pregnant. Your health care provider needs to know if you have any of these conditions: agitation or nervousness; diabetes; glaucoma; heart disease; high blood pressure; a history of substance abuse; kidney disease; a lung disease called Primary Pulmonary Hypertension; have taken an MAOI like Eldepryl, Marplan, Nardil, or Parnate in last 14 days; thyroid disease; an unusual or allergic reaction to phendimetrazine, other medicines, foods, dyes, or preservatives; pregnant or trying to become pregnant; breast-feeding. Notify your physician immediately if you become short of breath during your normal activities. Do not take this medicine within 6 hours of bedtime; it can keep you from falling asleep.
Concurrent use of phendimetrazine with other anorectic agents or CNS stimulants is contraindicated (see Drug Interactions). Phendimetrazine is not recommended for patients who have used any anorectic agent within the prior year.1
Phendimetrazine is contraindicated in patients who are in an agitated state.1 Sympathomimetics such as phendimetrazine may exacerbate the symptoms of bipolar disorder (e.g., mania), schizophrenia (e.g., psychosis), or anxiety disorders. Discontinuation of therapy may be required.
Because phendimetrazine is a sympathomimetic agent, it is contraindicated in thyroid disease patients with hyperthyroidism.1
Phendimetrazine is contraindicated in patients with glaucoma due to the ability of sympathetic stimulation to block aqueous outflow and raise intraocular pressure.1
Phendimetrazine is contraindicated in patients with a history of cardiac disease including coronary artery disease, cardiac arrhythmias, congestive heart failure, and uncontrolled hypertension. Use in patients with a history of cerebrovascular events including stroke are also contraindicated. Further, caution should be exercised in patients with even mild hypertension. Valvular heart disease has been associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine. Possible contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. The potential risk of possible serious adverse effects such as valvular heart disease should be assessed carefully against the potential benefit of weight loss. Baseline cardiac evaluation should be considered to detect preexisting valvular heart diseases prior to initiation of phendimetrazine treatment. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur.1
Phendimetrazine is contraindicated in patients with pulmonary hypertension. In a case-control epidemiological study, the use of anorectic agents, including phendimetrazine, was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder. The use of anorectic agents for longer than 3 months was associated with a 23-fold increase in the risk of developing pulmonary hypertension. Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded. The onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema suggest the possibility of occurrence of pulmonary hypertension. Under these circumstances, phendimetrazine should be immediately discontinued, and the patient should be evaluated for the possible presence of pulmonary hypertension. The potential risk of possible serious adverse effects such as pulmonary hypertension should be assessed carefully against the potential benefit of weight loss. Baseline cardiac evaluation should be considered to detect preexisting pulmonary hypertension prior to initiation of phendimetrazine treatment.1
Abrupt discontinuation of phendimetrazine after prolonged high doses may result in severe mental depression or extreme fatigue; sleep EEG changes have also been noted. Gradual withdrawal of therapy is recommended.1
Phendimetrazine is contraindicated for use in patients with a history of substance abuse.1 Phendimetrazine is chemically and pharmacologically related to the amphetamines which have been extensively abused. Obesity treatment with phendimetrazine should be tried only in weight reduction programs for whom alternative therapies, including repeated dietary reduction, exercise. Physiological dependence can occur with prolonged administration of phendimetrazine. The appetite suppressant is not recommend for use in those patients with a history of anorexia nervosa or other eating disorders. Risk versus benefit should be weighed in patients with a history of alcoholism, major depression, or suicidal ideation. Symptoms of chronic intoxication include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from other psychotic disorders, like schizophrenia. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion.
Safe and effective use in pediatric patients has not been established. Phendimetrazine is not recommended for neonates, infants, children, and adolescents under 17 years of age. Pediatric obesity is a chronic condition requiring long-term treatment, therefore short-term therapy with phendimetrazine is not recommended.1
Phendimetrazine is classified as FDA pregnancy risk category X. Safe use of phendimetrazine during pregnancy has not been established; there is no known indication for use of this drug during pregnancy. Phendimetrazine should not be taken by pregnant women or by women who are trying to become pregnant unless, in the opinion of the physician, the potential benefits outweigh the possible hazards.2
According to the manufacturer, it is not known whether phendimetrazine and its metabolites are excreted in breast milk. Because of the potential for serious adverse effects in the nursing infants, breast-feeding while taking phendimetrazine is contraindicated.2 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Use phendimetrazine cautiously in patients with diabetes mellitus. Insulin requirements may be altered in these patients when using phendimetrazine and changing dietary regimens.1
The use of phendimetrazine may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them. The debilitated or geriatric patient may be more susceptible to the CNS and sympathomimetic side effects of the phendimetrazine; use with caution in elderly patients. In addition, geriatric patients are more likely to have decreased renal function. Because phendimetrazine and its metabolites are excreted renally, use caution when administering to an elderly patient starting therapy at the lowest beneficial dose and monitoring renal function periodically.1
The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of sympathomimetic drugs. Because of this, and its effects on blood pressure, phendimetrazine should be discontinued several days prior to surgery.
Phendimetrazine is contraindicated in patients receiving MAOI therapy. Monoamine oxidase inhibitors (MAOIs) can prolong and intensify the cardiac stimulation and vasopressor effects of phendimetrazine (see Drug Interactions).1
Phendimetrazine has not been studied in patients with renal impairment. However, it is excreted in urine and exposure increases can be expected in patients with renal impairment. Caution is therefore warranted when phendimetrazine is administered to patients with renal impairment.1
This list may not include all possible contraindications. This medicine is intended to be used in addition to a healthy diet and exercise routine to achieve best results. This medicine is only indicated for short-term use and eventually your weight loss may level out. At that point, the drug will only help you maintain your new weight. Do not increase or in any way change your dose without first consulting your doctor. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizziness or fainting spells. Alcohol may increase dizziness and drowsiness.
Pregnancy: Phendimetrazine is classified as FDA pregnancy risk category X. Safe use of phendimetrazine during pregnancy has not been established; there is no known indication for use of this drug during pregnancy. Phendimetrazine should not be taken by pregnant women or by women who are trying to become pregnant unless, in the opinion of the physician, the potential benefits outweigh the possible hazards.2
Breast-feeding: According to the manufacturer, it is not known whether phendimetrazine and its metabolites are excreted in breast milk. Because of the potential for serious adverse effects in the nursing infants, breast-feeding while taking phendimetrazine is contraindicated.2 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Drug Interactions: Possible interactions include: medicines for diabetes or blood pressure, MAOIs, thyroid hormones and bupropion. This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
Do not take this medicine with any of the following medications: MAOIs like Eldepryl, Marplan, Nardil, and Parnate; medicines for colds or breathing difficulties like pseudoephedrine or phenylephrine; procarbazine; sibutramine; stimulants like amphetamines, phenidates, or modafinil. Do not take phendimetrazine if you are pregnant.
Phendimetrazine is a phenylalkaline sympathomimetic agent.2 All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The safety of phendimetrazine when used with other anorexiants such as amphetamine, benzphetamine, dexfenfluramine, dextroamphetamine, diethylpropion, ephedrine, fenfluramine, or phentermine is controversial and concurrent use should be avoided. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia. Similarly, phendimetrazine should not be used in combination with OTC preparations and herbal products that may contain ephedra alkaloids or Ma huang.
Concurrent use of dronabinol, THC or nabilone  with sympathomimetics (e.g., amphetamine, cocaine, or other sympathomimetics) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0—2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Sibutramine is contraindicated in patients taking other centrally-acting appetite suppressant drugs, including phendimetrazine.2
Phendimetrazine has vasopressor effects and can decrease the antihypertensive effect of guanethidine. Phendimetrazine may displace guanethidine from the neuron and antagonize the neuronal blockade caused by guanethidine.2
Monoamine oxidase inhibitors (MAOIs), or drugs that possess MAO-inhibiting activity such as furazolidone , linezolid , or procarbazine , can prolong and intensify the cardiac stimulation and vasopressor effects of phendimetrazine. Phenelzine and tranylcypromine  appear to produce the greatest risk since these two MAOIs also have intrinsic amphetamine-like activity. In the presence of MAOIs, phendimetrazine and other drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. It is unclear if selegiline, an inhibitor of MAO type B, can also predispose to this reaction. Phendimetrazine should not be administered during or within 14 days following the use of most MAOIs or drugs with MAO-inhibiting activity.2 However, rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; serious reactions with sympathomimetics are not ordinarily expected. However, because a case of elevated blood pressure occurred during use of rasagiline and a sympathomimetic ophthalmic preparation, caution is advised when rasagiline is administered with sympathomimetics.
The pressor response to some sympathomimetics is exaggerated in patients currently receiving tricyclic antidepressants. Concomitant use of tricyclic antidepressants with sympathomimetics, including phendimetrazine, should be avoided whenever possible.3452
Phendimetrazine is a sympathomimetic agent. Sympathomimetics may increase blood sugar via stimulation of beta2-receptors which leads to increased glycogenolysis.6 A pharmacodynamic interaction with antidiabetic agents may occur. Patients receiving antidiabetic agents should be closely monitored for loss of diabetic control when therapy with sympathomimetic agents is instituted. Conversely, diabetic patients may have decreased requirements of insulins, sulfonylureas or other antidiabetic agents in association with the use of phendimetrazine and the concomitant dietary regimen and weight loss.7 As long as blood glucose is carefully monitored to avoid hypoglycemia or hyperglycemia, it appears that phendimetrazine can be used concurrently.
Halogenated anesthetics sensitize the myocardium to the effects of sympathomimetics. Chronic use of sympathomimetics prior to halogenated anesthetics may result in cardiac arrhythmias. Phendimetrazine should be discontinued several days prior to surgery using halogenated anesthetics.89101112
The pharmacologic effects of phendimetrazine are similar to amphetamines.2 Amphetamines do not relieve cognitive impairment that results from ethanol intoxication, even though subjective improvements in motor performance have been noted on concomitant ingestion by patients. Ethanol containing beverages should generally be avoided while taking psychostimulants.13
Caution is advised when using thyroid hormones in combination with phendimetrazine; co-administration of sympathomimetics and thyroid hormones can enhance the cardiovascular effects of both agents. Patients with coronary artery disease have an increased risk of developing coronary insufficiency from either agent. Use of these agents concomitantly may increase this risk even further.1415162
Atomoxetine has been reported to increase blood pressure and heart rate, probably via inhibition of norepinephrine reuptake.17 Due to an additive pharmacodynamic effect, phendimetrazine and atomoxetine should be used together cautiously, particular in patients with a history of cardiac disease. Consider monitoring heart rate and blood pressure at baseline and regularly throughout treatment if these agents must be used together.
Bupropion is associated with a dose-related risk of seizures.18 Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; 18 seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary.
This list may not include all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
Adverse Reactions: Blurred vision or other eye problems; changes in sexual ability or desire; constipation or diarrhea; difficulty sleeping; dry mouth; flushing; headache; nausea; sweating.
Call your health care provider immediately if you are experiencing any signs of chest pain, palpitations; depression or severe changes in mood; increased blood pressure; irritability; nervousness or restlessness; painful urination; severe dizziness; vomiting.
Patients can develop tolerance to the anorectic effect of phendimetrazine within a few weeks. The mechanism of tolerance appears to be pharmacodynamic in nature; higher doses of phendimetrazine are required to produce the same response. When tolerance develops to the anorexiant effects, it is generally recommended that phendimetrazine be discontinued rather than the dose increased. The maximum recommended dose should not be exceeded.1
Anorexigens have been reported to be associated with the occurrence of serious regurgitant cardiac valvulopathy, including disease of the mitral, aortic, and/or tricuspid valves. In addition, phendimetrazine has been associated with other cardiac adverse events including palpitations, sinus tachycardia, hypertension, and ischemic events. Primary pulmonary hypertension (PPH), a rare, frequently fatal disease of the lungs, has also been found to occur with increased frequency in patients receiving anorexigens. The initial symptom of PPH is usually dyspnea. Other initial symptoms include: angina pectoris, syncope, or peripheral edema. Patients should be advised to report immediately any deterioration in exercise tolerance. Phendimetrazine should be discontinued in patients who develop new, unexplained symptoms of dyspnea, angina pectoris or chest pain (unspecified), syncope, or peripheral edema.1
Other adverse reactions that may occur or have been reported with phendimetrazine include abdominal pain, agitation, blurred vision, constipation, hyperhidrosis (sweating), diarrhea, dizziness, dyskinesia, dysphoria, dysuria, euphoria, flushing, headache, impotence (erectile dysfunction), increased urinary frequency, insomnia, libido decrease, libido increase, mydriasis, nausea/vomiting, ocular irritation, overstimulation, psychosis (rare) at recommended doses, restlessness, tremor, and xerostomia.1
Abuse of phendimetrazine may be associated with intense psychological dependence and severe social dysfunction. In some cases, patients have increased the dose of phendimetrazine several times that recommended. Abrupt withdrawal of phendimetrazine after prolonged high doses may result in extreme fatigue or mental depression; sleep EEG changes have also been noted. Signs and symptoms of chronic use of anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. Psychosis or hallucinations, which can often clinically indistinguishable from schizophrenia, is the most severe manifestation of chronic intoxication.1
This list may not include all possible adverse reactions or side effects. Call your health care provider immediately if you are experiencing any signs of an allergic reaction: skin rash, itching or hives, swelling of the face, lips, or tongue, blue tint to skin, chest tightness, pain, difficulty breathing, wheezing, dizziness, red, a swollen painful area/areas on the leg.
Storage: Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.
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