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Drug Interactions between danaparoid and Excedrin Extra Strength

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

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Interactions between your drugs

Major

aspirin danaparoid

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine) and danaparoid

GENERALLY AVOID: In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during low molecular weight heparin (LMWH) or heparinoid therapy may be increased by the concomitant use of other drugs that affect coagulation, including nonsteroidal anti-inflammatory drugs (NSAIDs). The development of epidural and spinal hematoma can lead to long-term or permanent paralysis.

GENERALLY AVOID: Theoretically, NSAIDs may potentiate the risk of bleeding complications associated with LMWH or heparinoid therapy. NSAIDs interfere with platelet adhesion and aggregation and may prolong bleeding time in healthy individuals. While these effects are generally slight and of relatively short duration with most NSAIDs (except aspirin) at recommended dosages, they may be of pronounced clinical significance when combined with the inhibitory effects of LMWHs or heparinoids on the clotting cascade. However, little clinical data exist regarding an actual interaction. In a controlled, randomized prospective study, 60 patients undergoing total hip replacement received enoxaparin (40 mg subcutaneously 12 hours pre- and every 24 hours postoperatively for 10 days) and analgesia with either ketorolac (30 mg IM on induction of anesthesia and every 24 hours postoperatively for 4 days) or an opioid plus acetaminophen. The authors reported no significant differences between the two groups for intraoperative blood loss, postoperative drainage, transfusion requirements, bruising, wound oozing, and leg swelling. However, there have been anecdotal reports of hemorrhagic complications in surgical patients treated with NSAIDs alone and in combination with a LMWH. In addition, NSAIDs are known to cause dose-related gastrointestinal bleeding, which may be complicated by anticoagulant therapy.

MANAGEMENT: Products containing NSAIDs, especially if given chronically and in high dosages, should preferably be avoided in patients receiving LMWHs or heparinoids. Close clinical and laboratory observation for bleeding complications is recommended if concurrent therapy is necessary. In patients undergoing neuraxial intervention, coadministration of these agents should be approached with caution and only after thorough assessment of risks and benefits. Besides bleeding complications, patients should also be monitored frequently for signs and symptoms of neurologic impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), and bowel or bladder dysfunction.

References

  1. Bang CJ, Riedel B, Talstad I, Berstad A "Interaction between heparin and acetylsalicylic acid on gastric mucosal and skin bleeding in humans." Scand J Gastroenterol 27 (1992): 489-94
  2. "Product Information. Lovenox (enoxaparin)." Rhone Poulenc Rorer PROD (2002):
  3. Walker AM "Predictors of bleeding during heparin therapy." JAMA 244 (1980): 1209-12
  4. Heiden D, Rodvien R, Mielke CH "Heparin bleeding, platelet dysfunction, and aspirin." JAMA 246 (1981): 330-1
  5. Theroux P, Ouimet H, McCans J, et al. "Aspirin, heparin, or both to treat acute unstable angina." N Engl J Med 319 (1988): 1105-6
  6. "Product Information. Fragmin (dalteparin)." Pharmacia and Upjohn PROD (2001):
  7. Weale AE, Warwick DJ, Durant N, Prothero D "Is there a clinical interaction between low molecular weight heparin and non-steroidal analgesics after total hip replacement?" Ann R Coll Surg Engl 77 (1995): 35-7
  8. Price AJ, Frcpath DO "Is there a clinical interaction between low molecular weight heparin and non-steroidal analgesics after total hip replacement?" Ann R Coll Surg Engl 77 (1995): 395
  9. "Product Information. Orgaran (danaparoid)." Organon PROD (2001):
  10. "Product Information. Normiflo (ardeparin)." Wyeth-Ayerst Laboratories PROD (2001):
  11. Klinkhardt U, Breddin HK, Esslinger HU, Haas S, Kalatzis A, Harder S "Interaction between the LMWH reviparin and aspirin in healthy volunteers." Br J Clin Pharmacol 49 (2000): 337-41
  12. "Product Information. Innohep (tinzaparin)." DuPont Pharmaceuticals PROD (2001):
View all 12 references

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Minor

aspirin caffeine

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine) and Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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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Drug and food interactions

Major

acetaminophen food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Moderate

aspirin food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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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Minor

caffeine food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy 16 (1996): 1046-52

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Minor

aspirin food

Applies to: Excedrin Extra Strength (acetaminophen / aspirin / caffeine)

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

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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