Skip to main content

Drug Interactions between Exaprin and lithium

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

lithium salicylamide

Applies to: lithium and Exaprin (acetaminophen / aspirin / caffeine / salicylamide)

MONITOR CLOSELY: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase serum lithium levels and induce toxicity in some patients. The exact mechanism of interaction is unknown, but is thought to involve inhibition of renal prostaglandin synthesis by NSAIDs, resulting in decreased renal blood flow and lithium excretion. There have been numerous published reports of lithium toxicity, including severe cases, following the introduction of various NSAIDs including diclofenac, ibuprofen, indomethacin, ketorolac, mefenamic acid, piroxicam, and COX-2 inhibitors. However, pharmacokinetic studies have been somewhat inconsistent, with no significant effects reported for benoxaprofen and etodolac, and up to a 58% increase in serum lithium levels reported for indomethacin. Both decreased serum concentrations of lithium and no effect have been reported for sulindac and aspirin. The interaction is apparently subject to marked interpatient variability.

MANAGEMENT: Given the narrow therapeutic index of lithium, caution is advised during coadministration with NSAIDs, particularly in the elderly or patients with other risk factors (e.g., sodium restriction; renal impairment; congestive heart failure; dehydration; concomitant use of diuretics, ACE inhibitors, or angiotensin II receptor antagonists). Close monitoring for clinical signs of lithium toxicity is recommended if concomitant treatment with NSAIDs is required. Serum lithium levels should be checked every 4 to 5 days after starting an NSAID until the extent of any potential interaction can be evaluated. A reduction in lithium dosage may be needed in some cases. Renal function should also be monitored regularly. Patients should be advised to seek medical attention if they experience potential signs and symptoms of lithium toxicity such as drowsiness, dizziness, confusion, muscle weakness, vomiting, diarrhea, polydipsia, polyuria, tinnitus, tremor, ataxia, and blurred vision.

References (44)
  1. Ragheb M, Ban TA, Buchanan D, Frolich JC (1980) "Interaction of indomethacin and ibuprofen with lithium in manic patients under a steady-state lithium level." J Clin Psychiatry, 41, p. 397-8
  2. Ragheb M (1987) "Ibuprofen can increase serum lithium level in lithium-treated patients." J Clin Psychiatry, 48, p. 161-3
  3. Herschberg SN, Sierles FS (1983) "Indomethacin-induced lithium toxicity." Am Fam Physician, 28, p. 155-7
  4. Reimann IW, Diener U, Frolich JC (1983) "Indomethacin but not aspirin increases plasma lithium ion levels." Arch Gen Psychiatry, 40, p. 283-6
  5. Ragheb M, Powell AL (1986) "Lithium interaction with sulindac and naproxen." J Clin Psychopharmacol, 6, p. 150-4
  6. Furnell MM, Davies J (1985) "The effect of sulindac on lithium therapy." Drug Intell Clin Pharm, 19, p. 374-6
  7. Reimann IW, Frolich JC (1981) "Effects of diclofenac on lithium kinetics." Clin Pharmacol Ther, 30, p. 348-52
  8. Ragheb M (1990) "The clinical significance of lithium-nonsteroidal anti-inflammatory drug interactions." J Clin Psychopharmacol, 10, p. 350-4
  9. Khan IH (1991) "Lithium and non-steroidal anti-inflammatory drugs." Br Med J, 302, p. 1537-8
  10. Gadallah MF, Feinstein EI, Massry SG (1988) "Lithium intoxication: clinical course and therapeutic considerations." Miner Electrolyte Metab, 14, p. 146-9
  11. Kamlana SH, Kerry RJ, Khan IA (1980) "Lithium: some drug interactions." Practitioner, 224, p. 1291-2
  12. Ragheb M (1990) "The interaction of lithium with phenylbutazone in bipolar affective patients." J Clin Psychopharmacol, 10, p. 149-50
  13. Walbridge DG, Bazire SR (1985) "An interaction between lithium carbonate and piroxicam presenting as lithium toxicity." Br J Psychiatry, 147, p. 206-7
  14. Shelley RK (1987) "Lithium toxicity and mefenamic acid: a possible interaction and the role of prostaglandin inhibition." Br J Psychiatry, 151, p. 847-8
  15. MacDonald J, Neale TJ (1988) "Toxic interaction of lithium carbonate and mefenamic acid." Br Med J, 297, p. 1339
  16. Nadarajah J, Stein GS (1985) "Piroxicam induced lithium toxicity." Ann Rheum Dis, 44, p. 502
  17. Kerry RJ, Owen G, Michaelson S (1983) "Possible toxic interaction between lithium and piroxicam." Lancet, 1, p. 418-9
  18. (2002) "Product Information. Eskalith (lithium)." SmithKline Beecham
  19. Harrison TM, Davies DW, Norris CM (1986) "Lithium carbonate and piroxicam." Br J Psychiatry, 149, p. 124-5
  20. Shelley RK (1986) "Lithium and piroxicam." Br J Psychiatry, 148:, p. 343
  21. Langlois R, Paquette D (1994) "Increased serum lithium levels due to ketorolac therapy." Can Med Assoc J, 150, p. 1455-6
  22. Iyer V (1994) "Ketorolac (Toradol) induced lithium toxicity." Headache, 34, p. 442-4
  23. Brouwers JRBJ, Desmet PAGM (1994) "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet, 27, p. 462-85
  24. Stockley IH (1995) "Interactions between lithium and NSAIDs." Can Med Assoc J, 152, p. 152-3
  25. Finley PR, Warner MD, Peabody CA (1995) "Clinical relevance of drug interactions with lithium." Clin Pharmacokinet, 29, p. 172-91
  26. Hughes BM, Small RE, Brink D, Mckenzie ND (1997) "The effect of flurbiprofen on steady-state plasma lithium levels." Pharmacotherapy, 17, p. 113-20
  27. Chandragiri SS, Pasol E, Gallagher RM (1998) "Lithium, ACE inhibitors, NSAIDs, and verapamil - A possible fatal combination." Psychosomatics, 39, p. 281-2
  28. Turck D, Heinzel G, Luik G (2000) "Steady-state pharmacokinetics of lithium in healthy volunteers receiving concomitant meloxicam." Br J Clin Pharmacol, 50, p. 197-204
  29. Lundmark J, Gunnarsson T, Bengtsson F (2002) "A possible interaction between lithium and rofecoxib." Br J Clin Pharmacol, 53, p. 403-4
  30. Monji A, Maekawa T, Miura T, et al. (2002) "Interactions between lithium and non-steroidal antiinflammatory drugs." Clin Neuropharmacol, 25, p. 241-2
  31. (2003) "A life-threatening interaction between lithium and celecoxib." Br J Clin Pharmacol, 55, p. 413
  32. Gunja N, Graudins A, Dowsett R (2002) "Lithium toxicity: a potential interaction with celecoxib." Intern Med J, 32(9-10), p. 494
  33. Bennett WM (1997) "Drug interactions and consequences of sodium restriction." Am J Clin Nutr, 65, S678-81
  34. Alderman CP, Lindsay KS (1996) "Increased serum lithium concentration secondary to treatment with tiaprofenic acid and fosinopril." Ann Pharmacother, 30, p. 1411-3
  35. Phelan KM, Mosholder AD, Lu S (2003) "Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs." J Clin Psychiatry, 64, p. 1328-34
  36. Juurlink DN, Mamdani MM, Kopp A, Rochon PA, Shulman KI, Redelmeier DA (2004) "Drug-induced lithium toxicity in the elderly: a population-based study." J Am Geriatr Soc, 52, p. 794-8
  37. Ratz Bravo AE, Egger SS, Crespo S, Probst WL, Krahenbuhl S (2004) "Lithium intoxication as a result of an interaction with rofecoxib." Ann Pharmacother, 38, p. 1189-93
  38. Wilting I, Movig KL, Moolenaar M, et al. (2005) "Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice." Bipolar Disord, 7, p. 274-80
  39. Chen L, Pym H (2010) "Rapid onset of neurological symptoms and lithium toxicity on starting meloxicam." Aust N Z J Psychiatry, 44, p. 95
  40. De Winter S, Meersseman W, Verelst S, Willems L, Spriet I (2013) "Drug-related admissions due to interaction with an old drug, lithium." Acta Clin Belg, 68, p. 356-8
  41. Finley PR (2016) "Drug interactions with lithium: an update." Clin Pharmacokinet, 55, p. 925-41
  42. Hassan S, Khalid F, Alirhayim Z, Amer S (2013) "Lithium toxicity in the setting of nonsteroidal anti-inflammatory medications." Case Rep Nephrol, 2013, epub
  43. Frolich JC, Leftwich R, Ragheb M, Oates JA, Reimann I, Buchanan D (1979) "Indomethacin increases plasma lithium." Br Med J, 1, p. 1115-6
  44. Kelly CB, Cooper SJ (1991) "Toxic elevation of serum lithium concentration by non-steroidal anti-inflammatory drugs." Ulster Med J, 60, p. 240-2
Moderate

lithium caffeine

Applies to: lithium and Exaprin (acetaminophen / aspirin / caffeine / salicylamide)

MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

References (1)
  1. Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A (1995) "Caffeine withdrawal increases lithium blood levels." Biol Psychiatry, 37, p. 348-50
Moderate

aspirin salicylamide

Applies to: Exaprin (acetaminophen / aspirin / caffeine / salicylamide) and Exaprin (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 (22)
  1. Furst DE, Sarkissian E, Blocka K, et al. (1987) "Serum concentrations of salicylate and naproxen during concurrent therapy in patients with rheumatoid arthritis." Arthritis Rheum, 30, p. 1157-61
  2. Abdel-Rahman MS, Reddi AS, Curro FA, Turkall RM, Kadry AM, Hansrote JA (1991) "Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers." Can J Physiol Pharmacol, 69, p. 1436-42
  3. Gruber CM (1976) "Clinical pharmacology of fenoprofen: a review." J Rheumatol, 2, p. 8-17
  4. Cressman WA, Wortham GF, Plostnieks J (1976) "Absorption and excretion of tolemetin in man." Clin Pharmacol Ther, 19, p. 224-33
  5. Kwan KC, Breault GO, Davis RL, et al. (1978) "Effects of concomitant aspirin administration on the pharmacokinetics of indomethacin in man." J Pharmacokinet Biopharm, 6, p. 451-76
  6. Rubin A, Rodda BE, Warrick P, Gruber CM Jr, Ridolfo RS (1973) "Interactions of aspirin with nonsteroidal antiinflammatory drugs in man." Arthritis Rheum, 16, p. 635-45
  7. Brooks PM, Walker JJ, Bell MA, Buchanan WW, Rhymer AR (1975) "Indomethacin--aspirin interaction: a clinical appraisal." Br Med J, 3, p. 69-11
  8. Tempero KF, Cirillo VJ, Steelman SL (1977) "Diflunisal: a review of pharmacokinetic and pharmacodynamic properties, drug interactions, and special tolerability studies in humans." Br J Clin Pharmacol, 4, s31-6
  9. Willis JV, Kendall MJ, Jack DB (1980) "A study of the effect of aspirin on the pharmacokinetics of oral and intravenous diclofenac sodium." Eur J Clin Pharmacol, 18, p. 415-8
  10. Muller FO, Hundt HK, Muller DG (1977) "Pharmacokinetic and pharmacodynamic implications of long-term administration of non-steroidal anti-inflammatory agents." Int J Clin Pharmacol Biopharm, 15, p. 397-402
  11. Hobbs DC, Twomey TM (1979) "Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies." J Clin Pharmacol, 19, p. 270-81
  12. Pawlotsky Y, Chales G, Grosbois B, Miane B, Bourel M (1978) "Comparative interaction of aspirin with indomethacin and sulindac in chronic rheumatic diseases." Eur J Rheumatol Inflamm, 1, p. 18-20
  13. Segre EJ, Chaplin M, Forchielli E, Runkel R, Sevelius H (1973) "Naproxen-aspirin interactions in man." Clin Pharmacol Ther, 15, p. 374-9
  14. Bird HA, Hill J, Leatham P, Wright V (1986) "A study to determine the clinical relevance of the pharmacokinetic interaction between aspirin and diclofenac." Agents Actions, 18, p. 447-9
  15. Brooks PM, Khong T (1977) "Flurbiprofen-aspirin interaction: a double-blind crossover study." Curr Med Res Opin, 5, p. 53-7
  16. Grennan DM, Ferry DG, Ashworth ME, Kenny RE, Mackinnnon M (1979) "The aspirin-ibuprofen interaction in rheumatoid arthritis." Br J Clin Pharmacol, 8, p. 497-503
  17. Williams RL, Upton RA, Buskin JN, Jones RM (1981) "Ketoprofen-aspirin interactions." Clin Pharmacol Ther, 30, p. 226-31
  18. Kaiser DG, Brooks CD, Lomen PL (1986) "Pharmacokinetics of flurbiprofen." Am J Med, 80, p. 10-5
  19. Kahn SB, Hubsher JA (1983) "Effects of oxaprozin alone or in combination with aspirin on hemostasis and plasma protein binding." J Clin Pharmacol, 23, p. 139-46
  20. (2001) "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim
  21. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  22. Cerner Multum, Inc. "Australian Product Information."
Minor

lithium aspirin

Applies to: lithium and Exaprin (acetaminophen / aspirin / caffeine / salicylamide)

Most studies have shown that aspirin and other salicylates do not significantly affect the serum concentrations of lithium. However, one study reported a 22% reduction in lithium clearance in six healthy female subjects given intravenous sodium salicylate, and another study reported a 32% increase in mean serum lithium level in a healthy subject given aspirin for 5 days. In general, no particular precaution should be necessary when lithium is coadministered with salicylates.

References (4)
  1. Reimann IW, Diener U, Frolich JC (1983) "Indomethacin but not aspirin increases plasma lithium ion levels." Arch Gen Psychiatry, 40, p. 283-6
  2. Ragheb M (1990) "The clinical significance of lithium-nonsteroidal anti-inflammatory drug interactions." J Clin Psychopharmacol, 10, p. 350-4
  3. Johnson AG, Nguyen TV, Day RO (1994) "Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis." Ann Intern Med, 121, p. 289-300
  4. Phelan KM, Mosholder AD, Lu S (2003) "Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs." J Clin Psychiatry, 64, p. 1328-34
Minor

aspirin caffeine

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

lithium food

Applies to: lithium

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Moderate

aspirin food

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

salicylamide food

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

lithium food

Applies to: lithium

MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

References (1)
  1. Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A (1995) "Caffeine withdrawal increases lithium blood levels." Biol Psychiatry, 37, p. 348-50
Moderate

acetaminophen food

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

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: Exaprin (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 (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: Exaprin (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)
  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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer