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Drug Interactions between acetaminophen / aspirin / caffeine and ardeparin

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

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Interactions between your drugs

Major

aspirin ardeparin

Applies to: acetaminophen / aspirin / caffeine and ardeparin

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

aspirin caffeine

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

Drug and food interactions

Major

acetaminophen food

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

aspirin food

Applies to: 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)
  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn
Moderate

acetaminophen food

Applies to: acetaminophen / aspirin / caffeine

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38
Minor

caffeine food

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

aspirin food

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

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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