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Drug Interactions between doxycycline / omega-3 polyunsaturated fatty acids and Painaid

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

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Interactions between your drugs

Moderate

aspirin omega-3 polyunsaturated fatty acids

Applies to: Painaid (acetaminophen / aspirin / caffeine / salicylamide) and doxycycline / omega-3 polyunsaturated fatty acids

MONITOR: Omega-3 fatty acids (e.g., fish oil) may potentiate the pharmacologic effects of anticoagulants and other drugs that affect hemostasis such as platelet inhibitors, thrombin inhibitors, thrombolytic agents, dextran, and nonsteroidal anti-inflammatory drugs (NSAIDs). The exact mechanism of interaction is unknown. Omega-3 fatty acids may possess mild antiplatelet and hypocoagulant activities. In some studies, these substances have been shown to reduce thrombin generation and plasma levels of fibrinogen, prothrombin, and coagulation factors V, VII, and X. Prolongation of bleeding time has been demonstrated, although it did not exceed normal limits and did not produce clinically significant bleeding. The interaction was suspected in a case report of a 67-year-old woman treated with warfarin for 1.5 years who exhibited an increase in INR from 2.8 the previous month to 4.3 approximately one week after doubling her fish oil dosage from 1000 to 2000 mg/day. Prior to the increase, her INR had been stable and therapeutic for 5 months on warfarin 1.5 mg/day. The patient was advised to reduce her fish oil consumption to 1000 mg/day, while her warfarin dose was withheld for one day and then reduced to 1 mg alternating with 1.5 mg per day. Eight days later, her INR was subtherapeutic at 1.6, so the warfarin dosage was increased back to 1.5 mg/day. The patient's INR subsequently returned to therapeutic range.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or nutritional supplements. Patients using omega-3 fatty acids in combination with anticoagulants or other drugs that affect hemostasis should be advised of the potential for increased risk of bleeding complications.

References

  1. "Product Information. Omacor (omega-3 polyunsaturated fatty acids)." Abbott Pharmaceutical (2005):
  2. Vanschoonbeek K, Feijge MA, Paquay J, et al. "Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation." Arterioscler Thromb Vasc Biol 24 (2004): 1734-40
  3. Buckley MS, Goff AD, Knapp WE "Fish oil interaction with warfarin." Ann Pharmacother 38 (2004): 50-3
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. "Product Information. Vascepa (icosapent)." Amarin Pharmaceuticals Inc (2012):
  7. Li XL, Steiner M "Fish oil: a potent inhibitor of platelet adhesiveness." Blood 76 (1990): 938-45
View all 7 references

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Moderate

aspirin salicylamide

Applies to: Painaid (acetaminophen / aspirin / caffeine / salicylamide) and Painaid (acetaminophen / aspirin / caffeine / salicylamide)

MONITOR: The combined use of low-dose or high-dose aspirin with other nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. Aspirin at anti-inflammatory dosages or higher may also decrease the plasma concentrations of many NSAIDs. The decreases have ranged from none or small (piroxicam, meloxicam, naproxen, tolmetin) to substantial (flurbiprofen, ibuprofen). However, the therapeutic response does not appear to be affected. Investigators theorize that aspirin may displace NSAIDs from plasma protein binding sites, resulting in increased concentration of unbound, or free, drug available for clearance. The increase in NSAID free fraction, and possibly some contributory anti-inflammatory effect from aspirin, may account for the lack of overall effect on therapeutic response.

MANAGEMENT: Caution is advised if aspirin, particularly at anti-inflammatory dosages, is used with other NSAIDs. Concomitant administration of NSAIDs is considered contraindicated or not recommended with aspirin at analgesic/anti-inflammatory dosages by many NSAID manufacturers. During concomitant therapy, 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. 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
  2. Abdel-Rahman MS, Reddi AS, Curro FA, Turkall RM, Kadry AM, Hansrote JA "Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers." Can J Physiol Pharmacol 69 (1991): 1436-42
  3. Gruber CM "Clinical pharmacology of fenoprofen: a review." J Rheumatol 2 (1976): 8-17
  4. Cressman WA, Wortham GF, Plostnieks J "Absorption and excretion of tolemetin in man." Clin Pharmacol Ther 19 (1976): 224-33
  5. 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
  6. 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
  7. Brooks PM, Walker JJ, Bell MA, Buchanan WW, Rhymer AR "Indomethacin--aspirin interaction: a clinical appraisal." Br Med J 3 (1975): 69-11
  8. Tempero KF, Cirillo VJ, Steelman SL "Diflunisal: a review of pharmacokinetic and pharmacodynamic properties, drug interactions, and special tolerability studies in humans." Br J Clin Pharmacol 4 (1977): s31-6
  9. Willis JV, Kendall MJ, Jack DB "A study of the effect of aspirin on the pharmacokinetics of oral and intravenous diclofenac sodium." Eur J Clin Pharmacol 18 (1980): 415-8
  10. 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
  11. Hobbs DC, Twomey TM "Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies." J Clin Pharmacol 19 (1979): 270-81
  12. 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
  13. Segre EJ, Chaplin M, Forchielli E, Runkel R, Sevelius H "Naproxen-aspirin interactions in man." Clin Pharmacol Ther 15 (1973): 374-9
  14. Bird HA, Hill J, Leatham P, Wright V "A study to determine the clinical relevance of the pharmacokinetic interaction between aspirin and diclofenac." Agents Actions 18 (1986): 447-9
  15. Brooks PM, Khong T "Flurbiprofen-aspirin interaction: a double-blind crossover study." Curr Med Res Opin 5 (1977): 53-7
  16. 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
  17. Williams RL, Upton RA, Buskin JN, Jones RM "Ketoprofen-aspirin interactions." Clin Pharmacol Ther 30 (1981): 226-31
  18. Kaiser DG, Brooks CD, Lomen PL "Pharmacokinetics of flurbiprofen." Am J Med 80 (1986): 10-5
  19. Kahn SB, Hubsher JA "Effects of oxaprozin alone or in combination with aspirin on hemostasis and plasma protein binding." J Clin Pharmacol 23 (1983): 139-46
  20. "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim PROD (2001):
  21. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  22. Cerner Multum, Inc. "Australian Product Information." O 0
View all 22 references

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Minor

aspirin caffeine

Applies to: Painaid (acetaminophen / aspirin / caffeine / salicylamide) and Painaid (acetaminophen / aspirin / caffeine / salicylamide)

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: Painaid (acetaminophen / aspirin / caffeine / salicylamide)

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: Painaid (acetaminophen / aspirin / caffeine / salicylamide)

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

salicylamide food

Applies to: Painaid (acetaminophen / aspirin / caffeine / salicylamide)

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

doxycycline food

Applies to: doxycycline / omega-3 polyunsaturated fatty acids

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ "Interactions with the absorption of tetracyclines." Drugs 11 (1976): 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand 191 (1972): 409-11
  3. Venho VM, Salonen RO, Mattila MJ "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol 14 (1978): 277-80
  4. "Product Information. Minocin (minocycline)." Lederle Laboratories PROD (2002):
  5. Campbell NR, Hasinoff BB "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol 31 (1991): 251-5
  6. Bateman FJ "Effects of tetracyclines." Br Med J 4 (1970): 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K "Interference of iron with the absorption of tetracyclines in man." Br Med J 4 (1970): 532-4
  8. Greenberger NJ "Absorption of tetracyclines: interference by iron." Ann Intern Med 74 (1971): 792-3
  9. Neuvonen PJ, Penttila O "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol 7 (1974): 361-3
  10. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  11. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
View all 11 references

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Minor

caffeine food

Applies to: Painaid (acetaminophen / aspirin / caffeine / salicylamide)

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

doxycycline food

Applies to: doxycycline / omega-3 polyunsaturated fatty acids

Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.

References

  1. Neuvonen PJ, Penttila O, Roos M, Tirkkonen J "Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man." Int J Clin Pharmacol Biopharm 14 (1976): 303-7

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Minor

aspirin food

Applies to: Painaid (acetaminophen / aspirin / caffeine / salicylamide)

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.

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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

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