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Drug Interactions between Exaprin and Minizide

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

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Interactions between your drugs

Moderate

prazosin aspirin

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

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the antihypertensive effect of prazosin. The proposed mechanism is NSAID-induced inhibition of prostaglandin synthesis. Data are available for indomethacin. A similar interaction is expected with other NSAIDs.

MANAGEMENT: The patient's blood pressure should be monitored during coadministration, and the dosage adjusted as necessary.

References

  1. Rubin P, Jackson G, Blaschke T (1980) "Studies on the clinical pharmacology of prazosin. II: The influence of indomethacin and of propranolol on the action and disposition of prazosin." Br J Clin Pharmacol, 10, p. 33-9
  2. Radack KL, Deck CC, Bloomfield SS (1987) "Ibuprofen interferes with the efficacy of antihypertensive drugs: a randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen." Ann Intern Med, 107, p. 628-35

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Moderate

prazosin polythiazide

Applies to: Minizide (polythiazide / prazosin) and Minizide (polythiazide / prazosin)

MONITOR: The hypotensive effects of thiazide diuretics and alpha-adrenergic blockers may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Patients should be advised to take the alpha-blocker at bedtime and to notify their physician if they experience dizziness or syncope while awake.

References

  1. Achari R, Laddu A (1992) "Terazosin: a new alpha adrenoceptor blocking drug." J Clin Pharmacol, 32, p. 520-3
  2. Kuokkanen K, Mattila MJ (1975) "Demonstration of an additive antihypertensive effect of prazosin and polythiazide in out-patient." Curr Ther Res Clin Exp, 17, p. 431-6
  3. Pool JL (1991) "Combination antihypertensive therapy with terazosin and other antihypertensive agents: results of clinical trials." Am Heart J, 122, p. 926-31
  4. Cohen J (1991) "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J, 122, p. 919-25
  5. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
View all 5 references

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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

  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."
View all 22 references

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

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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

  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
View all 12 references

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Moderate

prazosin food

Applies to: Minizide (polythiazide / prazosin)

GENERALLY AVOID: The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects. Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction. The mechanism has not been determined. Data exist for prazosin and other alpha adrenergic blockers are expected to interact also. In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

MANAGEMENT: Patients who develop a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake. All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

References

  1. Kawano Y, Abe H, Kojima S, Takishita S, Omae T (2000) "Interaction of alcohol and an a1-blocker on ambulatory blood pressure in patients with essential hypertension." Am J Hypertens, 13, p. 307-12
  2. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc

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

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Moderate

polythiazide food

Applies to: Minizide (polythiazide / prazosin)

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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

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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

  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

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