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Interactions with Drugs
Although the interactions for guarana are quite limited, there are numerous theoretical interactions based on guarana's caffeine content.
Caffeine combined with analgesics (pain relievers) has been reported to increase analgesic effects. For example, in treatment of migraine, a combination of N- acetyl- para- aminophenol acetaminophen (APAP), aspirin, and caffeine was found to be highly effective. Caffeine may also be beneficial when taken with ibuprofen or propyphenazone. Caffeine increases the peak plasma concentration, rate of absorption and bioavailability of aspirin. The addition of caffeine to aspirin has significant benefits on mood and performance. An aspirin/ butalbital/ caffeine/ codeine combination is considered superior to acetaminophen/ codeine in relieving oral surgery pain.
Caffeine is an adenosine antagonist and inhibits A1- receptors. Therefore the actions of caffeine are directly negated by adenosine and adenosine directly negates the effects of caffeine.
Alcohol consumption may increase caffeine serum concentrations and the risk of caffeine adverse effects.
Caffeine has been reported to have antiplatelet activity, and may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti- platelet drugs such as clopidogrel (Plavix®), and non- steroidal anti- inflammatory drugs (NSAIDS) such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®). Caffeine was also shown to attenuate the hemodynamic response to dipyridamole, a rheologic agent that inhibits platelet aggregation.
Caffeine may also alter blood sugar levels. Caution is advised when using medications that may also alter blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Caffeine may interact with benzodiazepines. When lorazepam and caffeine were given and mental performance tests were administered and compared, the effect of caffeine counteracted both the effect of reducing anxiety and the reduction in mental performance caused by lorazepam alone. Caffeine with diazepam (Valium®) may produce similar results by counteracting the drowsy effects and mental slowness of diazepam. The caffeine in guarana may also negate the hypnotic effects of pentobarbital. Sedative doses may need to be monitored.
Concomitant use of guarana may increase the inotropic effects of beta- adrenergic agonists.
Caffeine may alter the effects of carbamazepine (Tegretol®) and reduce the bioavailability. Consult with a qualified healthcare professional, including a pharmacist, as dosing adjustments may be necessary.
The antihistamine cimetidine (Tagamet®) may decrease caffeine clearance by inhibiting the microsomal metabolism of caffeine. Caution is advised in patients taking cimetidine along with caffeine or guarana.
Concomitant use of central nervous system stimulants and caffeine may increase the risk of stimulant adverse effects.
Caffeine may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be decreased or increased in the blood, and alter the intended effects. Patients taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions. Examples of agents that may interact include riluzole or fluvoxamine
Numerous agents alter the clearance, metabolism, and pharmacokinetics of caffeine when taken concurrently. For instance, when caffeine is taken with the steroid agent dexamethasone (Decadron®), the clearance of caffeine may increase. Antibacterial agents such as enoxacin may significantly inhibit caffeine elimination. Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine. Methoxsalen and mexiletine have been shown to decrease the clearance of caffeine. Concomitant use of birth control pills and caffeine may increase serum caffeine concentrations and increase the risk of adverse effects, as birth control pills decrease the rate of caffeine clearance. Disulfiram decreased clearance of caffeine in normal volunteers. Caffeine administration in patients pretreated with quinolones (norfloxacin or pipimidic acid) may result in decreased caffeine clearance. Caffeine degradation may be impaired by phenytoin (Dilantin®), an anticonvulsant drug.
Ephedrine in combination with guarana may increase blood pressure and therefore the risk of stroke and other cardiovascular events. Thermogenic synergism between ephedrine and caffeine may enhance the activity of ephedrine. Theoretically, pseudoephedrine (Sudafed®) would be expected to have the same effect on blood pressure when used in combination with guarana.
Caffeine may enhance the effectiveness of ergotamine tartrate (Cafergot®) in the treatment of migraine headaches. Caffeine may enhance topically applied (on the skin) hydrocortisone in the treatment of atopic dermatitis.
In preterm infants, caffeine has been found to be equivalent to theophylline in altering erythropoietin production, a hormone made in the kidneys. Theophylline is also used as a bronchodilator agent, and given to asthmatics. Caffeine may decrease total body clearance and elimination rate of theophylline. Caution is advised.
In a case report, esmolol was an effective treatment of caffeine toxicity resulting from a suicide attempt of ingesting excessive amounts of caffeine.
Caffeine may increase the renal (kidney) clearance of lithium and may reduce the plasma levels in stabilized patients. Abrupt discontinuation of a consistent caffeine intake may cause an increase in lithium tremors and an increase in serum lithium levels. Monitoring of doses may be necessary.
Although not well studied in humans, caffeine and monoamine oxidase inhibitors (MAOIs) may cause encephalopathy (degenerative brain disease), neuromuscular irritability, hypotension (low blood pressure), sinus tachycardia (increased heartbeat), rhabdomyolysis (potentially fatal disease involving destruction or degeneration of skeletal muscle) and hyperthermia (abnormally high body temperature). Consult with a qualified healthcare professional, including a pharmacist, to check for any interactions.
Caffeine may have additive effects on cardiovascular parameters when taken with nicotine. Concomitant consumption of caffeine and cigarettes during pregnancy may place the developing fetus at higher risk for diminished growth.
The combination of phenylpropanolamine and caffeine caused a manic psychosis in one woman with no previous history of mental disturbances. It is noted that phenylpropanolamine can increase the peak levels reached by caffeine by almost four- fold. An additive increase in blood pressure has occurred when using the combination of phenylpropanolamine and caffeine. Caution is advised.
Terbinafine (Lamisil®) is an antifungal agent that may increase serum caffeine concentrations and increase the risk of adverse effects. Caution is advised when taking terbinafine concurrently with caffeine.
Interactions with Herbs & Dietary Supplements
Herb and supplement interactions associated with guarana are predominantly theoretical and generally based upon the adverse effect profile of caffeine.
Caffeine may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
Caffeine might increase or decrease blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
Bitter orange may add to the possible hypertensive (blood pressure increasing) effects of caffeine. Caution is advised in patients with high blood pressure or those taking other herbs that have blood pressure altering effects.
Caffeine may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may become too low in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.
Caffeine may increase the flow of urine (diuresis), and may have additive effects with other herbs or supplements that have diuretic effects.
Caffeine may interact with herbs with estrogenic effects; caffeine metabolism was inhibited in postmenopausal women using hormone replacement estrogen.
Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine. Caution is advised.
Caffeine and monoamine oxidase inhibitors (MAOIs) may cause encephalopathy (degenerative brain disease), neuromuscular irritability, hypotension (low blood pressure), sinus tachycardia (increase heartbeat), rhabdomyolysis (potentially fatal disease involving destruction or degeneration of skeletal muscle), and hyperthermia (abnormally high body temperature).
Additive effects on cardiovascular parameters may occur with nicotine or tobacco. Concomitant consumption of caffeine and cigarettes during pregnancy may place the developing fetus at higher risk for diminished growth.