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Drug Interactions between diphenhydramine / naproxen and Pravigard Pac

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

naproxen aspirin

Applies to: diphenhydramine / naproxen and Pravigard Pac (aspirin / pravastatin)

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 Unpublished single-dose trials with ibuprofen 400 mg indicate that interference with aspirin's antiplatelet activity, as measured by thromboxane B2 (TXB2) levels and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: 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 indomethacin and naproxen.

MANAGEMENT: Until more information is available, patients receiving low-dose aspirin for cardioprotection should avoid the regular use of NSAIDs including ibuprofen, indomethacin, naproxen, and tiaprofenic acid. Occasional, single use may be 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. If routine NSAID therapy is necessary, 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. 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

  1. 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
  2. Furst DE, Sarkissian E, Blocka K, et al. "Serum concentrations of salicylate and naproxen during concurrent therapy in patients with rheumatoid arthritis." Arthritis Rheum 30 (1987): 1157-61
  3. Kwan KC, Breault GO, Davis RL, et al. "Effects of concomitant aspirin administration on the pharmacokinetics of indomethacin in man." J Pharmacokinet Biopharm 6 (1978): 451-76
  4. Rubin A, Rodda BE, Warrick P, Gruber CM Jr, Ridolfo RS "Interactions of aspirin with nonsteroidal antiinflammatory drugs in man." Arthritis Rheum 16 (1973): 635-45
  5. Brooks PM, Walker JJ, Bell MA, Buchanan WW, Rhymer AR "Indomethacin--aspirin interaction: a clinical appraisal." Br Med J 3 (1975): 69-11
  6. Muller FO, Hundt HK, Muller DG "Pharmacokinetic and pharmacodynamic implications of long-term administration of non-steroidal anti-inflammatory agents." Int J Clin Pharmacol Biopharm 15 (1977): 397-402
  7. Pawlotsky Y, Chales G, Grosbois B, Miane B, Bourel M "Comparative interaction of aspirin with indomethacin and sulindac in chronic rheumatic diseases." Eur J Rheumatol Inflamm 1 (1978): 18-20
  8. Segre EJ, Chaplin M, Forchielli E, Runkel R, Sevelius H "Naproxen-aspirin interactions in man." Clin Pharmacol Ther 15 (1973): 374-9
  9. 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
  10. Schafer AI "Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis." J Clin Pharmacol 35 (1995): 209-19
  11. 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
  12. 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
  13. MacDonald TM, Wei L "Effect of ibuprofen on cardioprotective effect of aspirin." Lancet 361 (2003): 573-4
  14. 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
  15. Bates ER, Mukherjee D, Lau WC "Drug-drug interactions involving antiplatelet agents." Eur Heart J 24 (2003): 1707-9
  16. 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
  17. 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
  18. 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
  19. "Concomitant use of ibuprofen and aspirin." J Pain Palliat Care Pharmacother 21 (2007): 73-4
  20. 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
  21. 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):
  22. Rao GH, Johnson GG, Reddy KR, White JG "Ibuprofen protects platelet cycloosygenase from irreversible inhibition by aspirin." Arteriosclerosis 3 (1983): 383-8
View all 22 references

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Drug and food interactions

Moderate

naproxen food

Applies to: diphenhydramine / naproxen

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

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Moderate

aspirin food

Applies to: Pravigard Pac (aspirin / pravastatin)

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

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Moderate

diphenhydrAMINE food

Applies to: diphenhydramine / naproxen

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Moderate

pravastatin food

Applies to: Pravigard Pac (aspirin / pravastatin)

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

References

  1. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb PROD (2001):
  2. "Product Information. Zocor (simvastatin)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  5. "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals (2002):
  6. "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Cerner Multum, Inc. "Australian Product Information." O 0
  9. "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
View all 9 references

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Minor

aspirin food

Applies to: Pravigard Pac (aspirin / pravastatin)

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

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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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.

Duplication

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:

  • diphenhydramine/naproxen
  • Pravigard Pac (aspirin/pravastatin)

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

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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