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Drug Interactions between Cafgesic and pemetrexed

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

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Moderate

salicylamide PEMEtrexed

Applies to: Cafgesic (acetaminophen / caffeine / phenyltoloxamine / salicylamide) and pemetrexed

ADJUST DOSING INTERVAL: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the plasma concentrations of pemetrexed. The mechanism has not been described but may be related to NSAID inhibition of renal prostaglandins. Use of NSAIDs has been associated with nephropathy manifested as elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. Since pemetrexed is primarily eliminated unchanged by renal excretion, coadministration with NSAIDs may result in delayed and/or decreased clearance. Daily ibuprofen dosage of 400 mg four times a day has been shown to reduce pemetrexed clearance by about 20% in patients with normal renal function, whereas aspirin at 325 mg every 6 hours did not. The effect of higher dosages of ibuprofen or aspirin is unknown.

MANAGEMENT: Ibuprofen at 400 mg and aspirin at 325 mg four times a day, or less, may be used with pemetrexed in patients with normal renal function. However, caution is advised in patients with mild to moderate renal insufficiency (creatinine clearance 45 to 79 mL/min). These patients should avoid taking NSAIDs with short elimination half-lives (e.g., diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, mefenamic acid, sulindac, tolmetin, low dosages of salicylates) 2 days before to 2 days after pemetrexed administration. If concomitant administration is necessary, patients should be monitored closely for toxicity, especially myelosuppression, nephrotoxicity, and gastrointestinal toxicity. In the absence of data regarding use with NSAIDs with longer half-lives, withholding NSAID dosing for at least 5 days before to 2 days after pemetrexed administration is recommended.

References

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  4. Shah GM, Muhalwas KK, Winer RL "Renal papillary necrosis due to ibuprofen." Arthritis Rheum 24 (1981): 1208-10
  5. Fong HJ, Cohen AH "Ibuprofen-induced acute renal failure with acute tubular necrosis." Am J Nephrol 2 (1982): 28-31
  6. Gary NE, Dodelson R, Eisinger RP "Indomethacin-associated acute renal failure." Am J Med 69 (1980): 135-6
  7. Blackshear JL, Davidman M, Stillman MT "Identification of risk for renal insufficiency from nonsteroidal anti-inflammatory drugs." Arch Intern Med 143 (1983): 1130-4
  8. Poitirt TI "Reversible renal failure associated with ibuprofen: case report and review of the literature." Drug Intell Clin Pharm 18 (1984): 27-32
  9. Moss AH, Riley R, Murgo A, Skaff LA "Over-the-counter ibuprofen and nephrotic syndrome." Ann Intern Med 105 (1986): 303
  10. Bonney SL, Northington RS, Hedrich DA, Walker BR "Renal safety of two analgesics used over the counter: ibuprofen and aspirin." Clin Pharmacol Ther 40 (1986): 373-7
  11. Zawada ET "Renal consequences of nonsteroidal antiinflammatory drugs." Postgrad Med J 71 (1982): 223-30
  12. Munn E, Lynn KL, Bailey RR "Renal papillary necrosis following regular consumption of non-steroidal anti-inflammatory drugs." N Z Med J 95 (1982): 213-4
  13. McCarthy JT, Torres VE, Romero JC, et al. "Acute intrinsic renal failure induced by indomethacin." Mayo Clin Proc 57 (1982): 289-96
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  15. Morgenstern SJ, Bruns FJ, Fraley DS, et al. "Ibuprofen-associated lipoid nephrosis without interstitial nephritis." Am J Kidney Dis 14 (1989): 50-2
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  17. Boiskin I, Saven A, Mendez M, Raja RM "Indomethacin and the nephrotic syndrome." Ann Intern Med 106 (1987): 776-7
  18. Sennesael J, Van den Houte K, Verbeelen D "Reversible membranous glomerulonephritis associated with ketoprofen." Clin Nephrol 26 (1986): 213-5
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  20. Schwarz A, Krause PH, Keller F, et al. "Granulomatous interstitial nephritis after nonsteroidal anti-inflammatory drugs." Am J Nephrol 8 (1988): 410-6
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  28. Reeve PA, Moshiri M, Bell GD "Pulmonary oedema, jaundice and renal impairment with naproxen." Br J Rheumatol 26 (1987): 70-1
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  32. Lomvardias S, Pinn VW, Wadhwa ML, et al. "Nephrotic syndrome associated with sulindac." N Engl J Med 304 (1981): 424
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  36. Chatterjee GP "Nephrotic syndrome induced by tolmetin." JAMA 246 (1981): 1589
  37. Katz SM, Capaldo R, Everts EA, DiGregorio JG "Tolmetin: association with reversible renal failure and acute interstitial nephritis." JAMA 246 (1981): 243-5
  38. Wellborne FR, Claypool RG, Copley JB "Nephrotic range pseudoproteinuria in a tolmetin-treated patient." Clin Nephrol 19 (1983): 211-2
  39. Pascoe MD, Gordon GD, Temple-Camp CR "Tolmetin-induced acute renal failure." S Afr Med J 70 (1986): 232-3
  40. Tietjen DP "Recurrence and specificity of nephrotic syndrome due to tolmetin." Am J Med 87 (1989): 354-5
  41. Kimberly RP, Plotz PH "Aspirin-induced depression of renal function." N Engl J Med 296 (1977): 418-24
  42. Riegger GA, Kahles HW, Elsner D, Kromer EP, Kochsiek K "Effects of acetylsalicylic acid on renal function in patients with chronic heart failure." Am J Med 90 (1991): 571-5
  43. Murray MD, Greene PK, Brater DC, et al. "Effects of flurbiprofen on renal function in patients with moderate renal insufficiency." Br J Clin Pharmacol 33 (1992): 385-93
  44. Aitken HA, Burns JW, McArdle CS, Kenny GNC "Effects of ketorolac trometamol on renal function." Br J Anaesth 68 (1992): 481-5
  45. Boras-Uber LA, Brackett NC Jr "Ketorolac-induced acute renal failure." Am J Med 92 (1992): 450-2
  46. Carmichael J, Shankel SW "Effects of nonsteroidal anti-inflammatory drugs on prostaglandins and renal function." Am J Med 78 (1985): 992-1000
  47. Perazella MA, Buller GK "Can ibuprofen cause acute renal failure in a normal individual? A case of acute overdose." Am J Kidney Dis 18 (1991): 600-2
  48. Bergamo RR, Cominelli F, Kopple JD, Zipser RD "Comparative acute effects of aspirin, diflunisal, ibuprofen and indomethacin on renal function in healthy men." Am J Nephrol 9 (1989): 460-3
  49. Berg KJ, Talseth T "Acute renal effects of sulindac and indomethacin in chronic renal failure." Clin Pharmacol Ther 37 (1985): 447-52
  50. Shand DG, Epstein C, Kinberg-Calhoun J, et al. "The effect of etodolac administration on renal function in patients with arthritis." J Clin Pharmacol 26 (1986): 269-74
  51. Feinfeld DA, Olesnicky L, Pirani CL, Appel GB "Nephrotic syndrome associated with use of the nonsteroidal anti-inflammatory drugs: case report and review of the literature." Nephron 37 (1984): 174-9
  52. Chan XM "Fatal renal failure due to indomethacin." Lancet 2 (1987): 340
  53. Maher JF "Analgesic nephropathy. Observations, interpretations, and perspective on the low incidence in America." Am J Med 76 (1984): 345-8
  54. Kaufhold J, Wilkowski M, McCabe K "Flurbiprofen-associated acute tubulointerstitial nephritis." Am J Nephrol 11 (1991): 144-6
  55. Colome Nafria E, Solans R, Espinach J, Delgadillo J, Fonollosa V "Renal papillary necrosis induced by flurbiprofen ." DICP 25 (1991): 870-1
  56. Beun GD, Leunissen KM, Van Breda Vriesman PJ, Van Hooff JP, Grave W "Isolated minimal change nephropathy associated with diclofenac." Br Med J (Clin Res Ed) 295 (1987): 182-3
  57. Schwartz J, Altshuler E, Madjar J, Habot B "Acute renal failure associated with diclofenac treatment in an elderly woman ." J Am Geriatr Soc 36 (1988): 482
  58. Tattersall J, Greenwood R, Farrington K "Membranous nephropathy associated with diclofenac ." Postgrad Med J 68 (1992): 392-3
  59. Hannedouche T, Dehaine V, Noel LH, Jungers P "Acute tubular necrosis associated with acute pyelonephritis and concomitant diclofenac therapy ." Clin Nephrol 28 (1987): 103-4
  60. Rossi E, Ferraccioli GF, Cavalieri F, Menta R, Dall'Aglio PP, Migone L "Diclofenac-associated acute renal failure. Report of 2 cases." Nephron 40 (1985): 491-3
  61. Wong F, Massie D, Hsu P, Dudley F "Indomethacin-induced renal dysfunction in patients with well- compensated cirrhosis." Gastroenterology 104 (1993): 869-76
  62. Pearce CJ, Gonzalez FM, Wallin JD "Renal failure and hyperkalemia associated with ketorolac tromethamine." Arch Intern Med 153 (1993): 1000-2
  63. Fong J, Gora ML "Reversible renal insufficiency following ketorolac therapy." Ann Pharmacother 27 (1993): 510-2
  64. Jick H, Derby LE, Garcia Rodriguez LA, Jick SS, Dean AD "Nonsteroidal antiinflammatory drugs and certain rare, serious adverse events: a cohort study." Pharmacotherapy 13 (1993): 212-7
  65. Frais MA, Burgess ED, Mitchell LB "Piroxicam-induced renal failure and hyperkalemia." Ann Intern Med 99 (1983): 129-30
  66. Mitnick PD, Klein WJ, Jr "Piroxicam-induced renal disease." Arch Intern Med 144 (1984): 63-4
  67. Loeffler M, Hanson G, Philp T "Piroxicam-induced renal failure following relief of chronic retention." Br J Urol 63 (1989): 438-9
  68. Goebel KM, Mueller-Brodmann W "Reversible overt nephropathy with Henoch-Schonlein purpura due to piroxicam." Br Med J (Clin Res Ed) 284 (1982): 311-2
  69. Fellner SK "Piroxicam-induced acute interstitial nephritis and minimal-change nephrotic syndrome." Am J Nephrol 5 (1985): 142-3
  70. Sarma PS "Fatal acute renal failure after piroxicam." Clin Nephrol 31 (1989): 54
  71. Gerber D "Adverse reactions of piroxicam." Drug Intell Clin Pharm 21 (1987): 707-10
  72. Brater DC, Brown-Cartwright D, Anderson SA, Uaamnuichai M "Effect of high-dose etodolac on renal function." Clin Pharmacol Ther 42 (1987): 283-9
  73. Mitnick PD, Greenberg A, DeOreo PB, Weiner BM, Coffman TM, Walker BR, Agus ZS, Goldfarb S "Effects of two nonsteroidal anti-inflammatory drugs, indomethacin and oxaprozin, on the kidney." Clin Pharmacol Ther 28 (1980): 680-9
  74. Quan DJ, Kayser SR "Ketorolac induced acute renal failure following a single dose." J Toxicol Clin Toxicol 32 (1994): 305-9
  75. Haragsim L, Dalal R, Bagga H, Bastani B "Ketorolac-induced acute renal failure and hyperkalemia: report of three cases." Am J Kidney Dis 24 (1994): 578-80
  76. Perneger TV, Whelton PK, Klag MJ "Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs." N Engl J Med 331 (1994): 1675-9
  77. van Biljon G "Reversible renal failure associated with ibuprofen in a child. A case report." S Afr Med J 76 (1989): 34-5
  78. Delmas PD "Non-steroidal anti-inflammatory drugs and renal function." Br J Rheumatol 34 Suppl (1995): 25-8
  79. Segasothy M, Chin GL, Sia KK, Zulfiqar A, Samad SA "Chronic nephrotoxicity of anti-inflammatory drugs used in the treatment of arthritis." Br J Rheumatol 34 (1995): 162-5
  80. Whelton A "Renal effects of over-the-counter analgesics." J Clin Pharmacol 35 (1995): 454-63
  81. Blackwell E, Loughlin K, Dumler F, Smythe M "Nabumetone-associated interstitial nephritis." Pharmacotherapy 15 (1995): 669-72
  82. Jonsson CE, Ericsson F "Impairment of renal function after treatment of a burn patient with diclofenac, a non-steroidal anti-inflammatory drug." Burns 21 (1995): 471-3
  83. Kelley M, Bastani B "Ketorolac-induced acute renal failure and hyperkalemia." Clin Nephrol 44 (1995): 276-7
  84. Radford RG, Holley KE, Grande JP, Larson TS, Wagoner RD, Donadio JV, Mccarthy JT "Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs." JAMA 276 (1996): 466-9
  85. Buck ML, Norwood VF "Ketorolac-induced acute renal failure in a previously healthy adolescent." Pediatrics 98 (1996): 294-6
  86. Ogawa M, Ueda S, Hamano Y, Ito K, Saisho H, Akikusa B "Membranous nephropathy associated with oxaprozin treatment." Nephron 74 (1996): 439-40
  87. Feldman HI, Kinman JL, Berlin JA, et al. "Parenteral ketorolac: the risk for acute renal failure." Ann Intern Med 126 (1997): 193-9
  88. Buller GK, Perazella MA "Acute renal failure and ketorolac." Ann Intern Med 127 (1997): 493
  89. Feldman HI, Kinman JL, Strom BL "Acute renal failure and ketorolac." Ann Intern Med 127 (1997): 493-4
  90. "Product Information. Celebrex (celecoxib)." Searle PROD (2001):
  91. Cangiano JL, Figueroa J, Palmer R "Renal hemodynamic effects of nabumetone, sulindac, and placebo in patients with osteoarthritis." Clin Ther 21 (1999): 503-12
  92. Wolf G, Porth J, Stahl RA "Acute renal failure associated with rofecoxib." Ann Intern Med 133 (2000): 394
  93. "Product Information. Alimta (pemetrexed)." Lilly, Eli and Company (2004):
View all 93 references

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Drug and food interactions

Major

acetaminophen food

Applies to: Cafgesic (acetaminophen / caffeine / phenyltoloxamine / 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

phenyltoloxamine food

Applies to: Cafgesic (acetaminophen / caffeine / phenyltoloxamine / salicylamide)

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

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

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Moderate

salicylamide food

Applies to: Cafgesic (acetaminophen / caffeine / phenyltoloxamine / 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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Minor

caffeine food

Applies to: Cafgesic (acetaminophen / caffeine / phenyltoloxamine / 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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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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