Allegra-D Interactions
Alpha-blockers
- Ammonium Chloride
Antacids
Antidiabetic Agents
Beta-blockers
- Bromocriptine
- Caffeine
Cardiac glycosides
Central-acting adrenergic agents
- Citric Acid; Sodium Citrate
- Cocaine
- Cyclopropane
- Dronabinol, THC
Ergot Alkaloids
- Erythromycin
- food
- Furazolidone
- grapefruit juice
- Green Tea
- Guarana
Halogenated anesthetics
- Ketoconazole
- Linezolid
- Mecamylamine
- Methazolamide
Monoamine oxidase inhibitors (MAOIs)
Nitrates
- Potassium Citrate
- Procarbazine
- Reserpine
- Rifampin
- Sodium Acetate
- Sodium Bicarbonate
- Sodium Lactate
- St. John’s Wort, Hypericum perforatum
Sympathomimetics
- Theophylline, Aminophylline
Thyroid hormones
Tricyclic antidepressants
Allegra-D Interactions
Unlike terfenadine, fexofenadine has not been associated with QT prolongation or ventricular arrhythmias when coadministered with erythromycin or ketoconazole. In two separate studies of 24 healthy subjects, fexofenadine 120 mg twice daily (twice the recommended dose) was co-administered with erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily for seven days. No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine alone or in combination with potent CYP 3A4 inhibitors, erythromycin or ketoconazole. Erythromycin increased steady-state fexofenadine peak concentrations by 82% and increased AUC by 109%. Ketoconazole increased steady-state fexofenadine peak concentrations by 135% and increased AUC by 164%. Fexofenadine had no effect on the pharmacokinetics of erythromycin or ketoconazole. These studies indicate that ketoconazole or erythromycin coadministration enhances fexofenadine gastrointestinal absorption. This observed increase in fexofenadine bioavailability may be due to transport-related effects, such as p-glycoprotein. In vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion. According to the manufacturer, the associated changes in fexofenadine plasma levels following erythromycin or ketoconazole were within the range of plasma levels achieved in adequate and well-controlled clinical trials. Given the magnitude of the increases in AUC and that the contribution of CYP 3A4 metabolism to the elimination of systemically absorbed fexofenadine has not been clearly elucidated (see Pharmacokinetics), it is prudent to use caution and monitor patients receiving fexofenadine and erythromycin or ketoconazole until additional data are available.
Coadministration with antacids (containing aluminum or magnesium) within 15 minutes decreases the AUC and Cmax of fexofenadine by 41% and 43%, respectively. Separate administration is recommended.
Due to the pseudoephedrine component, fexofenadine; pseudoephedrine products should not be used by patients receiving monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping use of an MAO inhibitor. MAOIs, or other drugs that possess MAO-inhibiting activity such as furazolidone, linezolid, or procarbazine, can prolong and intensify the cardiac stimulation and vasopressor effects of pseudoephedrine. Of the MAOIs, phenelzine and tranylcypromine appear to produce the greatest risk since these agents also have intrinsic amphetamine-like activity. In the presence of MAOIs, pseudoephedrine 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.
Although fexofenadine is considered a ‘non-sedating’ H1-blocker, sedation has been noted in individual patients receiving fexofenadine or other second generation, non-sedating H1-blockers. For this reason, it would be prudent to monitor for drowsiness during concurrent use with other CNS depressants such as tricyclic antidepressants, barbiturates, benzodiazepines, opiate agonists, antipsychotics, ethanol, other H1-blockers, and anxiolytics, sedatives, and hypnotics.
Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics including cocaine by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of amphetamines, cocaine, or other sympathomimetics. Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity.
The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects of produced by reserpine, alpha-blockers, beta-blockers, central-acting adrenergic agents (e.g., clonidine, guanfacine, guanabenz, methyldopa), and mecamylamine. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with cardiac glycosides. Pseudoephedrine may also interact with many tricyclic antidepressants resulting in increased risk for severe headaches or cardiovascular toxicity.
Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of the nitrate.
Where possible, avoid concurrent use of pseudoephedrine-containing products and the ergot alkaloids. Although no data are available, it is possible that concomitant use of pseudoephedrine with ergotamine or dihydroergotamine could cause additive and possibly severe peripheral vasoconstriction. Some ergot alkaloids, notably ergotamine and, to a lesser extent, ergonovine, may produce peripheral vasoconstriction due to alpha-receptor agonism in the peripheral circulation. Hypertension, headache, myocardial ectopy, and seizures have occurred when bromocriptine, an ergot derivative, was combined with various sympathomimetics. Pseudoephedrine use should be avoided in patients on ergot alkaloids or bromocriptine whenever possible.
Pseudoephedrine renal elimination is susceptible to changes in urinary pH. Ammonium chloride, by acidifying the urine, increases the elimination of pseudoephedrine while sodium bicarbonate, a urinary alkalinizer, allows for increased tubular reabsorption of pseudoephedrine. While the interaction with ammonium chloride is unlikely to be clinically significant, concomitant administration of pseudoephedrine with urinary alkalinizers such as sodium citrate, potassium citrate, sodium lactate, and sodium acetate may increase the likelihood of pseudoephedrine adverse reactions.
Pseudoephedrine may increase blood sugar via stimulation of beta2-receptors which leads to increased glycogenolysis. 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.
Methazolamide can decrease excretion and enhance the effects of pseudoephedrine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized pseudoephedrine available for renal tubular reabsorption. Use caution if methazolamide is coadministered; monitor for excessive pseudoephedrine-related adverse effects.
Drug interactions with St. John’s wort, Hypericum perforatum are unclear at this time. Some of the components of this herb have been shown to inhibit monoamine oxidase (MAO) in vitro, but in vivo activity is unclear. If St. John’s wort does have MAOI-like activities, it could potentially increase the cardiac stimulation and vasopressor effects of the sympathomimetics. St. John’s wort should be used cautiously with any sympathomimetic agent, including pseudoephedrine. In addition, conflicting studies have shown that St. John’s Wort may increase, decrease, or not change the plasma concentrations and AUC of fexofenadine. Results vary between single and multiple dose studies. The mechanisms proposed have included CYP3A4 induction and/or altered P-glycoprotein efflux transport of fexofenadine. The clinical importance of this theoretical interaction has not been established; further study is needed.
Concomitant use of sympathomimetics and thyroid hormones can enhance the effects of either drug on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Combined use of these agents may further increase this risk.
Halogenated anesthetics and cyclopropane may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Rifampin may decrease plasma concentrations of fexofenadine and potentially reduce its antihistaminic effects. A 6-day course of rifampin (600 mg/day) has been reported to increase the oral clearance of fexofenadine (single dose) by 2 to 3-fold in 24 healthy subjects. Rifampin does not alter the renal clearance or half-life of fexofenadine. In theory, rifampin may activate P-glycoprotein transport in the small intestine, and thereby decreases the oral absorption of fexofenadine (a substrate of P-glycoprotein transport). Although the therapeutic range of fexofenadine is broad, monitor for potential decreased therapeutic effects of fexofenadine if rifampin is initiated.
The administration of fexofenadine; pseudoephedrine products with food is not recommended; decreased drug bioavailability may occur. Administration of fexofenadine; pseudoephedrine products with a high-fat meal decreased the Cmax and AUC of fexofenadine by 46% and 42%, respectively; however, the rate and extent of pseudoephedrine absorption are not affected. Some fruit juices also appear to impair the absorption of fexofenadine. Apple juice, orange juice, and grapefruit juice have been reported to decrease the AUC and Cmax of fexofenadine by roughly 60 - 70%, but individual variability in the changes have been noted in various studies. Since these apparent interactions might result in a decrease the effectiveness of the drug, advise patients to avoid administration with these juices when possible. The mechanism of the interaction is proposed to be an inhibition of intestinal drug uptake transport systems by the juices, resulting in decreased systemic drug absorption.
Concurrent administration of caffeine with pseudoephedrine can produce excessive stimulatory effects such as nervousness, irritability, insomnia, or tremor. Other xanthines, such as theophylline, can interact in a similar way. Excessive caffeine ingestion should be avoided while taking pseudoephedrine concurrently. This includes ingestion of foods and beverages that contain high amounts of caffeine such as coffee, teas, green tea, colas, and chocolate and dietary supplements such as guarana.
[ Last revised: 1/4/2006 10:06:00 PM ]
References
. Allegra® (fexofenadine) package insert. Kansas City, MO: Aventis Pharmaceuticals; 2005 Oct.
Related entries
Syndicate
|
