Drug Interactions between Axotal and ibuprofen / phenylephrine
This report displays the potential drug interactions for the following 2 drugs:
- Axotal (aspirin/butalbital)
- ibuprofen/phenylephrine
Interactions between your drugs
ibuprofen aspirin
Applies to: ibuprofen / phenylephrine and Axotal (aspirin / butalbital)
GENERALLY AVOID: The antiplatelet and cardioprotective effect of low-dose aspirin may be antagonized by coadministration of some nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen has been specifically implicated, and there is evidence that others including indomethacin, naproxen, and tiaprofenic acid may also interact. The mechanism is competitive inhibition of platelet cyclooxygenase by certain NSAIDs, which, unlike aspirin, bind reversibly at the active site of the enzyme and cause a temporary rather than persistent depression of thromboxane formation and thromboxane-dependent platelet function. Unpublished single-dose trials with ibuprofen 400 mg indicate that interference with aspirin's antiplatelet activity, as measured by thromboxane B2 (TXB2) levels and platelet activation studies, occurs when ibuprofen is taken within 8 hours before or 30 minutes after dosing of immediate-release aspirin. One study showed that the antiplatelet effect of enteric-coated low-dose aspirin is attenuated when ibuprofen 400 mg is dosed 2, 7, and 12 hours after aspirin. In contrast, a placebo-controlled study found no clinically significant reduction of TXB2 inhibition when ibuprofen (400 mg three times a day) was coadministered with chewable, immediate-release aspirin (81 mg once a day) for 10 days in healthy volunteers. There are no clinical endpoint studies conducted specifically to evaluate the interaction. A retrospective study of 7107 heart patients discharged from hospitals between 1989 and 1997 with aspirin prescriptions found that those also taking ibuprofen were twice as likely to die during the study period as those taking aspirin alone or with other NSAIDs or acetaminophen. That translates to 12 extra deaths (3 heart-related deaths) a year for every 1000 patients treated. A subgroup analysis from a 5-year randomized, double-blind, placebo-controlled trial of 325 mg aspirin use on alternate days among 22,071 apparently healthy U.S. male physicians with prospective observational data on use of NSAIDs found that regular (>= 60 days/year) but not intermittent (1 to 59 days/year) use of NSAIDs inhibited the clinical benefits of aspirin on first myocardial infarction (MI). Specifically, regular users of NSAIDs in the aspirin group had a greater than 2-fold increased risk of MI, while regular users of NSAIDs in the placebo group had a nonsignificantly reduced risk of MI. There was no association between intermittent use of NSAIDs and subsequent development of MI among aspirin or placebo recipients.
MONITOR CLOSELY: The combined use of aspirin with NSAIDs in general may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. Pharmacokinetically, aspirin at anti-inflammatory dosages or higher has been shown to decrease the plasma concentrations of many NSAIDs, including ibuprofen. One study reported a mean 56% reduction in ibuprofen levels during coadministration of aspirin in seven rheumatoid arthritis patients. No change in the elimination half-life of ibuprofen was observed, which suggests an effect on absorption or protein binding of ibuprofen rather than excretion.
MANAGEMENT: Patients receiving low-dose aspirin for cardioprotection should avoid the regular use of ibuprofen and possibly other NSAIDs. Occasional use of ibuprofen is acceptable, as the risk from any attenuation of the antiplatelet effect of low-dose aspirin is likely to be minimal given the long-lasting effect of aspirin on platelets. In patients receiving immediate-release (not enteric-coated) aspirin, single doses of ibuprofen 400 mg may be used but should not be administered within 8 hours before or 30 minutes after the aspirin dose. There are currently no specific recommendations regarding the dosing and timing of single-dose ibuprofen in patients receiving enteric-coated low-dose aspirin. For patients requiring routine NSAID therapy with concomitant low-dose aspirin, diclofenac may be a viable alternative. In the retrospective study implicating ibuprofen, 75 mg twice daily of delayed-release diclofenac did not interfere with the antiplatelet activity of aspirin. Other noninterfering alternatives for pain include acetaminophen, celecoxib, or narcotic analgesics. In any case, caution is advised whenever aspirin is combined with a NSAID due to the potential for additive GI toxicity. Some authorities consider the concomitant use of aspirin with other NSAIDs, including ibuprofen, to be contraindicated due to the potential for additive adverse reactions (AU). However, other authorities restrict the contraindication to the concomitant use of aspirin at analgesic doses (i.e., above 75 mg daily) (UK). Patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as abdominal pain, bloating, sudden dizziness or lightheadedness, nausea, vomiting, hematemesis, anorexia, and melena.
References
- Livio M, Del Maschio A, Cerletti C, de Gaetano G "Indomethacin prevents the long-lasting inhibitory effect of aspirin on human platelet cyclo-oxygenase activity." Prostaglandins 23 (1982): 787-96
- Grennan DM, Ferry DG, Ashworth ME, Kenny RE, Mackinnnon M "The aspirin-ibuprofen interaction in rheumatoid arthritis." Br J Clin Pharmacol 8 (1979): 497-503
- Schafer AI "Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis." J Clin Pharmacol 35 (1995): 209-19
- Catella-Lawson F, Reilly MP, Kapoor SC, et al. "Cyclooxygenase inhibitors and the antiplatelet effects of aspirin." N Engl J Med 345 (2001): 1809-17
- Wilner KD, Rushing M, Walden C, et al. "Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers." J Clin Pharmacol 42 (2002): 1027-30
- MacDonald TM, Wei L "Effect of ibuprofen on cardioprotective effect of aspirin." Lancet 361 (2003): 573-4
- Kurth T, Glynn RJ, Walker AM, et al. "Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs." Circulation 108 (2003): 1191-5
- Bates ER, Mukherjee D, Lau WC "Drug-drug interactions involving antiplatelet agents." Eur Heart J 24 (2003): 1707-9
- Kimmel SE, Berlin JA, Reilly M, et al. "The effects of nonselective non-aspirin non-steroidal anti-inflammatory medications on the risk of nonfatal myocardial infarction and their interaction with aspirin." J Am Coll Cardiol 43 (2004): 985-90
- Cryer B, Berlin RG, Cooper SA, Hsu C, Wason S "Double-blind, randomized, parallel, placebo-controlled study of ibuprofen effects on thromboxane B(2) concentrations in aspirin-tereated healthy adult volunteers." Clin Ther 27 (2005): 185-91
- Capone ML, Sciulli MG, Tacconelli S, et al. "Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects." J Am Coll Cardiol 45 (2005): 1295-301
- Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
- "Concomitant use of ibuprofen and aspirin." J Pain Palliat Care Pharmacother 21 (2007): 73-4
- Cerner Multum, Inc. "Australian Product Information." O 0
- Gladding PA, Webster MW, Farrell HB, Zeng IS, Park R, Ruijne N "The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers." Am J Cardiol 101 (2008): 1060-3
- FDA. U.S. Food and Drug Administration "Information for healthcare professionals: concomitant use of ibuprofen and aspirin. New information [9/2006] - concomitant use of ibuprofen and aspirin. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125222." (2010):
- Rao GH, Johnson GG, Reddy KR, White JG "Ibuprofen protects platelet cycloosygenase from irreversible inhibition by aspirin." Arteriosclerosis 3 (1983): 383-8
Drug and food interactions
butalbital food
Applies to: Axotal (aspirin / butalbital)
GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.
MANAGEMENT: The combination of ethanol and barbiturates should be avoided.
References
- Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
- Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
- Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
- Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
- Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
ibuprofen food
Applies to: ibuprofen / phenylephrine
GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.
MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.
References
- "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):
aspirin food
Applies to: Axotal (aspirin / butalbital)
GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.
MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.
References
- "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):
phenylephrine food
Applies to: ibuprofen / phenylephrine
MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.
MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.
References
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
- Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
- "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
- "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
- "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
- "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
- "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
aspirin food
Applies to: Axotal (aspirin / butalbital)
One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.
References
- Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6
Therapeutic duplication warnings
Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.
Nonsteroidal anti-inflammatories
Therapeutic duplication
The recommended maximum number of medicines in the 'nonsteroidal anti-inflammatories' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'nonsteroidal anti-inflammatories' category:
- Axotal (aspirin/butalbital)
- ibuprofen/phenylephrine
Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Check Interactions
To view an interaction report containing 4 (or more) medications, please sign in or create an account.
Save Interactions List
Sign in to your account to save this drug interaction list.