Phentermine Interactions
Antidiabetic Agents
- Atomoxetine
- Dronabinol, THC
- Duloxetine
- Ethanol
- Furazolidone
- Guanadrel
- Guanethidine
Halogenated anesthetics
- Linezolid
- Methyldopa
Monoamine oxidase inhibitors (MAOIs)
Phenothiazines
- Procarbazine
Psychostimulants
- Reserpine
Selective serotonin reuptake inhibitors (SSRIs)
- Sibutramine
Sympathomimetics
Thyroid hormones
Tricyclic antidepressants
- Venlafaxine
Phentermine Interactions
The safety of phentermine when used with other anorexiant agents such as amphetamine, dexfenfluramine, dextroamphetamine, diethylpropion, ephedrine, fenfluramine, and sibutramine is controversial and concurrent use should be avoided. The role of phentermine in the production of cardiac valvulopathy when combined with dexfenfluramine, fenfluramine, or other medications for weight loss is uncertain. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. Similarly, because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics or psychostimulants for weight loss, including OTC preparations, and herbal products that may contain ephedra alkaloids or Ma huang.
Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity.
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 phentermine. Phenelzine and tranylcypromine appear to produce the greatest risk since these two MAOIs also have intrinsic amphetamine-like activity. In the presence of MAOIs, phentermine 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. Phentermine should not be administered during or within 14 days following the use of MAOIs or drugs with MAO-inhibiting activity.
Until more data are available, the combined use of phentermine and SSRIs should be avoided. While the combined use of phentermine with certain SSRIs (e.g., fluoxetine) has been of interest for the treatment of obesity, studies have generally not supported combined treatment due to a risk of significant weight-regain after discontinuation of use. Additionally, a few case reports suggest potential adverse effects from the combination.
In vitro data suggest that fluoxetine potentiates the anorectic and neurotoxic effects of phentermine; similar effects may occur with the use of other SSRIs. As a drug related to the amphetamines, phentermine should additionally be combined with SSRIs with caution due to the potential for excessive serotonin activity (i.e., ‘serotonin syndrome’). The slight MAOI activity of phentermine may also be of concern with SSRI use, since serotonin is deaminated by monoamine oxidase type A and increased serotonin activity may result from MAO inhibition. However, some experts have debated phentermine’s effect on MAO at therapeutic doses. Thus, while a mechanism of interaction between phentermine and SSRIs is unclear at this time, the potential for interaction exists based on current evidence.
Until more data are available, the combined use of phentermine with serotonin norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine) should be avoided. A few case reports suggest potential adverse effects from the combination of phentermine with drugs that augment the actions of serotonin. As a drug related to the amphetamines, phentermine may enhance the potential for excessive serotonin activity (i.e., ‘serotonin syndrome’). The slight MAOI activity of phentermine may also be of concern, since serotonin is deaminated by monoamine oxidase type A and increased serotonin activity may result from MAO inhibition. However, some experts have debated phentermine’s effect on MAO at therapeutic doses. Thus, while a mechanism of interaction between phentermine and serotonin norepinephrine reuptake inhibitors is unclear at this time, the potential for an interaction exists based on current evidence.
The pressor response to some sympathomimetics is exaggerated in patients currently receiving tricyclic antidepressants. Concomitant use of tricyclic antidepressants with sympathomimetics, including phentermine, should be avoided whenever possible.
Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as guanadrel, guanethidine, methyldopa or reserpine. Phentermine may displace guanethidine from the neuron and antagonize the neuronal blockade caused by guanethidine. Concomitant use of phentermine with methyldopa or reserpine may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Use caution in combining phentermine with antidiabetic agents. Phentermine exhibits sympathomimetic activity. Sympathomimetics may increase blood sugar via stimulation of beta2-receptors which leads to increased glycogenolysis. A pharmacodynamic interaction with antidiabetic agents may occur. Diabetic patients may have decreased requirements of insulins, sulfonylureas, or other antidiabetic agents in association with the use of phentermine and the concomitant dietary regimen and weight loss. As long as blood glucose is carefully monitored to avoid hypoglycemia or hyperglycemia, it appears that phentermine can be used concurrently.
Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery.
Concurrent use of phentermine and phenothiazines may antagonize the anorectic effects of phentermine. In addition, psychostimulants can aggravate psychotic states.
Although not studied, the concomitant use of ethanol and phentermine may result in an adverse reaction and should be avoided.
Phentermine, like other sympathomimetics, is contraindicated in selected patients with thyroid disease; caution should be used if coadministering thyroid hormones with phentermine.
Atomoxetine has been reported to increase blood pressure and heart rate, probably via inhibition of norepinephrine reuptake. Due to an additive pharmacodynamic effect, phentermine 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.
[ Last revised: 11/10/2004 4:22:00 PM ]
References
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. Strattera® (atomoxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2003 Sept.
. Elavil® (amitriptyline) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2000 Dec.
. Meridia® (sibutramine) package insert. North Chicago, IL: Abbott Laboratories; 2003 Oct.
. Tenuate® (diethylpropion hydrochloride) package insert. Lane Cove, NSW: Aventis Pharmaceuticals; 1998 Feb.
. Halothane, USP package insert. North Chicago, IL: Abbott Laboratories; 1998 Mar.
. Vivero LE, Anderson PO, Clark RF. A close look at fenfluramine and dexfenfluramine. J Emerg Med. 1998;16:197-205.
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. Fastin® (phentermine) package insert. Philadelphia, PA: Beecham Laboratories; 1987 Oct.
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