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Drug Interactions between aspirin / chlorpheniramine / dextromethorphan and Diovan HCT

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

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Interactions between your drugs

Moderate

aspirin hydroCHLOROthiazide

Applies to: aspirin / chlorpheniramine / dextromethorphan and Diovan HCT (hydrochlorothiazide / valsartan)

MONITOR: Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics may adversely affect renal function due to NSAID inhibition of the renal synthesis of prostaglandins that help maintain renal perfusion in dehydrated states. The risk may be increased in patients on dietary sodium restriction. At the same time, hypotensive effect of the diuretics may be reduced because inhibition of prostaglandins can lead to unopposed pressor activity and, consequently, elevation in blood pressure. Natriuretic and diuretic effects may also be reduced, as NSAIDs have been reported to cause sodium and water retention, which may account for the increased risk of congestive heart failure associated with the combination. One study showed an increase in the incidence density of congestive heart failure (in patients over 55 years of age) from 9.3 per 1,000 person-years in patients on diuretics to 23.3 per 1,000 person-years in patients on both diuretic and NSAID therapy. NSAIDs may also increase the risk of hyperkalemia associated with potassium-sparing diuretics.

MANAGEMENT: In patients receiving both diuretic and NSAID therapy, management consists of avoiding dehydration and carefully monitoring the patient's renal function and blood pressure. If renal insufficiency or hyperkalemia develops, both drugs should be discontinued until the condition is corrected.

References (33)
  1. Allan SG, Knox J, Kerr F (1981) "Interaction between diuretics and indomethacin." Br Med J, 283, p. 1611
  2. McCarthy JT, Torres VE, Romero JC, et al. (1982) "Acute intrinsic renal failure induced by indomethacin." Mayo Clin Proc, 57, p. 289-96
  3. Favre L, Glasson P, Vallotton MB (1982) "Reversible acute renal failure from combined triamterene and indomethacin." Ann Intern Med, 96, p. 317-20
  4. Poe TE, Scott RB, Keith JF Jr (1983) "Interaction of indomethacin with furosemide." J Fam Pract, 16, p. 610-6
  5. Ahmad S (1984) "Indomethacin-bumetanide interaction: an alert." Am J Cardiol, 54, p. 246-7
  6. Dixey JJ, Noormohamed FH, Lant AF, Brewerton DA (1987) "The effects of naproxen and sulindac on renal function and their interaction with hydrochlorothiazide and piretanide in man." Br J Clin Pharmacol, 23, p. 55-63
  7. Brater DC, Fox WR, Chennavasin P (1981) "Interaction studies with bumetanide and furosemide: effects of probenecid and of indomethacin on response to bumetanide in man." J Clin Pharmacol, 21, p. 647-53
  8. Smith DE, Brater DC, Lin ET, Benet LZ (1979) "Attenuation of furosemide's diuretic effect by indomethacin: pharmacokinetic evaluation." J Pharmacokinet Biopharm, 7, p. 265-74
  9. Mor R, Pitlik S, Rosenfeld JB (1983) "Indomethacin- and Moduretic--induced hyperkalemia." Isr J Med Sci, 19, p. 535-7
  10. Kaufman J, Hamburger R, Matheson J, Flamenbaum W (1981) "Bumetanide-induced diuresis and natriuresis: effect of prostaglandin synthetase inhibition." J Clin Pharmacol, 21, p. 663-7
  11. Favre L, Glasson P, Riondel A, Vallotton MB (1983) "Interaction of diuretics and non-steroidal anti-inflammatory drugs in man." Clin Sci, 64, p. 407-15
  12. Pedrinelli R, Magagna A, Arzilli F, et al. (1980) "Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension." Clin Pharmacol Ther, 28, p. 722-31
  13. Weinberg MS, Quigg RJ, Salant DJ, Bernard DB (1985) "Anuric renal failure precipitated by indomethacin and triamterene." Nephron, 40, p. 216-8
  14. Furst DE (1988) "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl, 17, p. 58-62
  15. Gehr T, Sica DA, Steigler BW, Marshall C (1990) "Interaction of triamterene-hydrochlorothiazide (T-H) and ibuprofen (I)." Clin Pharmacol Ther, 47, p. 200
  16. (2002) "Product Information. HydroDIURIL (hydrochlorothiazide)." Merck & Co., Inc
  17. Watkins J, Abbot EC, Hensby CN, Webster J, Dollery CT (1980) "Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin." Br Med J, 281, p. 702-5
  18. Salerno F, Lorenzano E, Maggi A, Badalamenti S, Minuz P, Degan M, Chinea B, Scotti A (1993) "Effects of imidazole-salicylate on renal function and the diuretic action of furosemide in cirrhotic patients with ascites." J Hepatol, 19, p. 279-84
  19. Ripley EB, Gehr TW, Wallace H, Wade J, Kish C, Sica DA (1994) "The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone." Int J Clin Pharmacol Ther, 32, p. 12-8
  20. Desaulles E, Schwartz J (1979) "A comparative study of the action of frusemide and methyclothiazide on renin release by rat kidney slices and the interaction with indomethacin." Br J Pharmacol, 65, p. 193-6
  21. Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV (1995) "Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol, 48, p. 247-51
  22. Gurwitz JH, Everitt DE, Monane M, et al. (1996) "The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons." J Gerontol A Biol Sci Med Sci, 51, m74-9
  23. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A (1998) "NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics." Arch Intern Med, 158, p. 1108-12
  24. Bartoli E, Arras S, Faedda R, Soggia G, Satta A, Olmeo NA (1980) "Blunting of furosemide diuresis by aspirin in man." J Clin Pharmacol, 20, p. 452-8
  25. Tobert MB, Ostaszewski T, Reger B, Meisinger MA, Cook TJ (1980) "Diflunisal-furosemide interaction." Clin Pharmacol Ther, 27, p. 289-90
  26. Planas R, Arroyo V, Rimola A, Perez-Ayuso RM, Rodes J (1983) "Acetylsalicylic acid suppresses the renal hemodynamic effect and reduces the diuretic action of furosemide in cirrhosis with ascites." Gastroenterology, 84, p. 247-52
  27. Wilson TW, McCauley FA, Wells HD (1986) "Effects of low-dose aspirin on responsses to furosemide." J Clin Pharmacol, 26, p. 100-5
  28. Valette H, Apoil E (1979) "Interaction between salicylate and two loop diuretics." Br J Clin Pharmacol, 8, p. 592-4
  29. Leary WP, Reyes AJ (1984) "Drug interactions with diuretics." S Afr Med J, 65, p. 455-61
  30. Bennett WM (1997) "Drug interactions and consequences of sodium restriction." Am J Clin Nutr, 65, S678-81
  31. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
  32. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  33. Perazella MA (2000) "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med, 109, p. 307-14
Moderate

aspirin valsartan

Applies to: aspirin / chlorpheniramine / dextromethorphan and Diovan HCT (hydrochlorothiazide / valsartan)

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effects of angiotensin II receptor antagonists. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure. Clinical data are limited.

MONITOR: Concomitant use of NSAIDs and angiotensin II receptor antagonists may cause deterioration in renal function, particularly in patients who are elderly or volume-depleted (including those on diuretic therapy) or have compromised renal function. Acute renal failure may occur, although effects are usually reversible. Chronic use of NSAIDs alone may be associated with renal toxicities, including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. Additionally, in patients with prerenal conditions whose renal perfusion may be dependent on the function of prostaglandins, NSAIDs may precipitate overt renal decompensation via a dose-related inhibition of prostaglandin synthesis. Angiotensin II receptor antagonists can further worsen renal function by blocking the effect of angiotensin II-mediated efferent arteriolar vasoconstriction, thereby decreasing glomerular filtration.

MANAGEMENT: Patients receiving angiotensin II receptor antagonists who require prolonged (greater than 1 week) concomitant therapy with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of dosage of the NSAID. Renal function should also be evaluated periodically during prolonged coadministration. The interaction is not expected to occur with low doses (e.g., low-dose aspirin) or intermittent short-term administration of NSAIDs.

References (4)
  1. 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
  2. (2002) "Product Information. Toradol (ketorolac)." Roche Laboratories
  3. "Multum Information Services, Inc. Expert Review Panel"
  4. (2001) "Product Information. Celebrex (celecoxib)." Searle
Moderate

chlorpheniramine dextromethorphan

Applies to: aspirin / chlorpheniramine / dextromethorphan and aspirin / chlorpheniramine / dextromethorphan

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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 (36)
  1. Hamilton MJ, Bush M, Smith P, Peck AW (1982) "The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man." Br J Clin Pharmacol, 14, p. 791-7
  2. Stambaugh JE, Lane C (1983) "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest, 1, p. 111-7
  3. Sotaniemi EA, Anttila M, Rautio A, et al. (1981) "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther, 29, p. 705-10
  4. Grabowski BS, Cady WJ, Young WW, Emery JF (1980) "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol, 18, p. 317-9
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF (1988) "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther, 43, p. 412-9
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  8. Naylor GJ, McHarg A (1977) "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J, 2, p. 22
  9. Stovner J, Endresen R (1965) "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand, 24, p. 223-7
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF (1984) "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol, 36, p. 244-7
  11. Feldman SA, Crawley BE (1970) "Interaction of diazepam with the muscle-relaxant drugs." Br Med J, 1, p. 336-8
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF (1988) "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl), 96, p. 63-6
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I (1989) "Midazolam-morphine sedative interaction in patients." Anesth Analg, 68, p. 282-5
  15. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
  16. Greiff JMC, Rowbotham D (1994) "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet, 27, p. 447-61
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G (1989) "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand, 80 Suppl, p. 95-8
  18. Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
  19. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
  20. (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
  21. (2001) "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc)
  22. (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
  23. (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
  24. (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
  25. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  26. (2001) "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical
  27. (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
  28. Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
  29. Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
  30. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
  31. (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
  32. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  33. Cerner Multum, Inc. "Australian Product Information."
  34. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  35. (2014) "Product Information. Belsomra (suvorexant)." Merck & Co., Inc
  36. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

Drug and food interactions

Moderate

chlorpheniramine food

Applies to: aspirin / chlorpheniramine / dextromethorphan

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

dextromethorphan food

Applies to: aspirin / chlorpheniramine / dextromethorphan

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

valsartan food

Applies to: Diovan HCT (hydrochlorothiazide / valsartan)

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

References (2)
  1. (2001) "Product Information. Cozaar (losartan)." Merck & Co., Inc
  2. (2001) "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals
Moderate

aspirin food

Applies to: aspirin / chlorpheniramine / dextromethorphan

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

hydroCHLOROthiazide food

Applies to: Diovan HCT (hydrochlorothiazide / valsartan)

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. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References (10)
  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
  9. (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
  10. (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
Minor

aspirin food

Applies to: aspirin / chlorpheniramine / dextromethorphan

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.

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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.

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