Buspirone Interactions
- Amiodarone
Anti-retroviral protease inhibitors
Antipsychotics
- Aprepitant
- Aspirin, ASA
Barbiturates
Benzodiazepines
- Buprenorphine
- Butorphanol
- Carbamazepine
- Chloral Hydrate
- Cimetidine
- Clarithromycin
- Dalfopristin; Quinupristin
- Delavirdine
- Dexamethasone
- Digoxin
- Diltiazem
- Dronabinol, THC
- Duloxetine
- Efavirenz
- Entacapone
- Erythromycin
- Ethanol
- Ethotoin
- food
- Fosphenytoin
- Furazolidone
- grapefruit juice
- Imatinib, STI-571
- Itraconazole
- Ketoconazole
- Linezolid
- Mifepristone, RU-486
Monoamine oxidase inhibitors (MAOIs)
- Nalbuphine
- Nefazodone
- Nicardipine
Opiate agonists
- Pentazocine
- Phenytoin
- Pramipexole
- Pregabalin
- Procarbazine
- Ranolazine
- Rifampin
- Ropinirole
Sedating H1-blockers
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-Receptor Agonists
- Tolcapone
- Tramadol
- Trazodone
- Troleandomycin
- Venlafaxine
- Verapamil
- Voriconazole
- Warfarin
- Zafirlukast
- Zaleplon
- Zileuton
- Zolpidem
Buspirone Interactions
Buspirone should be taken consistently with or without food because food decreases the presystemic clearance of buspirone. Grapefruit juice has been reported to significantly increase buspirone peak concentrations and AUC, probably through the inhibition of gut-wall CYP3A4 isoenzyme metabolism. There may be great variation in the significance of this effect among individuals. Subjective drowsiness and other side effects of buspirone may be increased with grapefruit juice ingestion. Patients receiving buspirone should be advised to avoid drinking large amounts of grapefruit juice.
Simultaneous use of buspirone with monoamine oxidase inhibitors (MAOIs) can increase blood pressure, so it is recommended that this combination be avoided. When switching drug therapy, there should be a 14-day delay after discontinuing a MAOI (e.g., isocarboxazid, phenelzine, tranylcypromine or selegiline) or a drug with MAOI-like actions (e.g., furazolidone or procarbazine) before initiating a serotonergic drug like buspirone treatment.
Linezolid is a reversible, non-selective MAO inhibitor. Concomitant use of linezolid and buspirone is not recommended; several cases of elevated blood pressure have been reported in patients in whom buspirone was added to a non-selective MAO-inhibitor regimen. At least 10 days should elapse between the discontinuation of linezolid and the institution of buspirone.
Buspirone can displace digoxin from plasma proteins, but the clinical significance of this effect has yet to be determined.
The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation. Concomitant use of buspirone and haloperidol results in increased serum concentrations of haloperidol, possibly due to competition in the oxidative dealkylation pathway of metabolism.
Substances that are potent inducers of hepatic cytochrome P450 isoenzyme CYP3A4, (e.g., barbiturates, dexamethasone, rifampin, or certain anticonvulsants like carbamazepine, phenytoin or fosphenytoin and possibly ethotoin, may increase the rate of buspirone metabolism. In a study of healthy volunteers, co-administration of buspirone with rifampin decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC) and pharmacodynamic effects of buspirone. An in vitro study indicated that buspirone did not displace highly protein-bound drugs such as phenytoin. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. In addition, CNS depressants like the barbiturates may also enhance drowsiness or CNS depression.
It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence. Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can increase the risk of sedation. Coadministration of buspirone with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine.
The combination of buspirone and ethanol or other CNS depressants can increase the risk for sedation. While formal studies of the interaction of the drug with alcohol indicate that buspirone does not increase alcohol-induced impairment in motor and mental performance, it is prudent to limit or avoid alcoholic beverages while taking buspirone. Other CNS depressants include buprenorphine, butorphanol, chloral hydrate, cannabinoids (e.g., dronabinol, THC), entacapone, nalbuphine, pentazocine, pramipexole, pregabalin, opiate agonists, ropinirole, the sedating H1-blockers, tolcapone, tramadol, tricyclic antidepressants, zaleplon and zolpidem.
Coadministration of buspirone with verapamil or diltiazem substantially increases the plasma concentrations (Cmax and AUC) of buspirone by about three-fold. The mechanism is probably related to the inhibition of CYP3A4 by these calcium channel blockers. Subjective drowsiness and other side effects of buspirone may be increased; buspirone dose adjustment may be necessary and should be based on clinical assessment. Similar interactions may occur with nicardipine.
The administration of nefazodone with buspirone has resulted in marked increases in plasma buspirone concentrations most likely due to CYP3A4 inhibition by nefazodone. Some patients receiving both drugs concurrently have reported lightheadedness, asthenia, dizziness, and drowsiness. If buspirone is to be administered concurrently with nefazodone, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended. Subsequent dosage adjustments should be based on clinical response.
Some clinicians feel that buspirone should be used very cautiously, with other serotonergic drugs such as the trazodone. However, there exist instances where these drug combinations are clinically beneficial. Until more data are available, careful monitoring should be undertaken when these combinations are used. Pharmacologically, buspirone is a serotonin agonist; trazodone blocks serotonin reuptake. Combined use of these drugs might lead to symptoms consistent with serotonin syndrome.The addition of fluoxetine to a regimen consisting of buspirone and trazodone was reported to result in an increase in anxiety-type symptoms in one patient. Additionally, there is one report suggesting that the concomitant use of trazodone and buspirone may have caused 3- to 6-fold elevations on SGPT (ALT) in a few patients; however, in a similar study, no such problems were reported.
Some clinicians feel that buspirone should be used very cautiously, with other serotonergic drugs such as the SSRIs, or the serotonin norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine). However, there exist instances where these drug combinations are clinically beneficial. Until more data are available, careful monitoring should be undertaken when these combinations are used. Pharmacologically, buspirone is a serotonin agonist; the SSRIs block serotonin reuptake. Combined use of these drugs might lead to symptoms consistent with serotonin syndrome. The addition of fluoxetine to a regimen consisting of buspirone and trazodone was reported to result in an increase in anxiety-type symptoms in one patient. Another patient developed a grand mal seizure while receiving the combination of buspirone and fluoxetine. CYP3A4 inhibitors such as fluvoxamine or fluoxetine may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response. Additionally, there is one report suggesting that the concomitant use of trazodone and buspirone may have caused 3- to 6-fold elevations on SGPT (ALT) in a few patients; however, in a similar study, no such problems were reported.
Although unlikely to occur with serotonin-receptor agonists (’triptans’ used for migraine headache) when given alone, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome. Pharmacologically, buspirone is a serotonin agonist, and use in conjunction with other serotonin agonists could result in serotonin syndrome. Patients receiving serotonin-receptor agonists and buspirone should be informed of the signs and symptoms of serotonin syndrome; although rare, serotonin excess is possible with concurrent use.
Pharmacokinetic data suggest that concomitant administration of itraconazole or ketoconazole and buspirone results in significant (up to 19-fold) increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. However, a wide interindividual variability in the extent of the interaction has been noted. Some patients receiving these drugs with buspirone concurrently have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (eg, 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. A similar reaction may occur when buspirone is combined with fluconazole, miconazole (IV), or voriconazole, but data are not yet available.
Pharmacokinetic data suggest that concomitant administration of erythromycin with buspirone results in significant (up to 6-fold) increases in buspirone AUC; the mechanism is probably reduced buspirone metabolism via CYP3A4. However, a wide interindividual variability in the extent of the interaction has been noted. Some patients receiving both drugs concurrently have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (eg, 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Similar interactions may occur when buspirone is combined with clarithromycin or troleandomycin.
When buspirone is administered with a potent inhibitor of CYP3A4 like ritonavir, a low dose of buspirone used cautiously is recommended. Some patients receiving drugs that are potent inhibitors of CYP3A4 with buspirone have reported lightheadedness, asthenia, dizziness, and drowsiness. If the two drugs are to be used in combination, a low dose of buspirone (e.g., 2.5 mg PO twice daily) is recommended. Subsequent dose adjustment of either drug should be based on clinical assessment. Several other anti-retroviral protease inhibitors also inhibit CYP3A4, and these may interact with buspirone in a similar manner.
Although data are not available, other CYP3A4 inhibitors not previously mentioned, such as amiodarone, aprepitant, cimetidine, dalfopristin; quinupristin, delavirdine, efavirenz (inducer or inhibitor), fluvoxamine, fluoxetine, imatinib, STI-571, mifepristone, RU-486, ranolazine, zafirlukast, or zileuton, may decrease systemic clearance of buspirone leading to increased or prolonged effects. This list is not inclusive of all agents that inhibit CYP3A4. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone (i.e., 2.5 mg PO twice daily) is recommended initially. Subsequent dosage adjustments should be based on clinical response.
In vitro studies showed that aspirin, ASA increased the plasma concentrations of free buspirone by 23%. In vivo interaction studies with these drugs have not been performed.
An in vitro study indicated that buspirone did not displace highly protein-bound drugs (e.g., warfarin) from plasma proteins. However, one case of prolonged prothrombin time when buspirone was added to the regimen of a patient stabilized on warfarin; however, the patient was also chronically receiving other drugs that might have been contributory to the event. Interactions with warfarin are expected to be rare.
[ Last revised: 3/1/2006 2:41:00 PM ]
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