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Drug Interactions between Actidose Plus Sorbitol and Phrenilin with Caffeine and Codeine

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

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Interactions between your drugs

Major

codeine butalbital

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine) and Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine)

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. US Food and Drug Administration (2016) FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf

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Moderate

acetaminophen charcoal

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine) and Actidose Plus Sorbitol (charcoal / sorbitol)

GENERALLY AVOID: Charcoal may reduce the absorption of many drugs and can absorb enterohepatically circulated drugs. Clinical utility may be the reduction either of the effects or of the toxicity of many drugs. Activated charcoal may adsorb any therapeutic agents administered while it is in the gastrointestinal tract.

MANAGEMENT: The regular ingestion of charcoal should be avoided by patients requiring maintenance medications. If concomitant use is necessary, the dosage or route of administration may need to be altered.

References

  1. Decker WJ, Shpall RA, Corby DG (1969) "Inhibition of aspirin absorption by activated charcoal and apomorphine." Clin Pharmacol Ther, 10, p. 710-3
  2. Knadler MP, Bergstrom RF, Callaghan JT, Obermeyer BD, Rubin A (1987) "Absorption studies of the H2-blocker nizatidine." Clin Pharmacol Ther, 42, p. 514-20
  3. Wing LM, Miners JO, Birkett DJ, et al. (1984) "Lidocaine disposition: sex differences and effects of cimetidine." Clin Pharmacol Ther, 35, p. 695-701
  4. Scheufler E, Bos I (1983) "Influence of peroral charcoal on pharmacokinetics and intestinal toxicity of intravenously given methotrexate." Arch Int Pharmacodyn Ther, 261, p. 180-5
  5. Gadgil SD, Damle SR, Advani SH, Vaidya AB (1982) "Effect of activated charcoal on the pharmacokinetics of high-dose methotrexate." Cancer Treat Rep, 66, p. 1169-71
  6. Park GD, Spector R, Goldberg MJ, Johnson GF (1986) "Expanded role of charcoal therapy in the poisoned and overdosed patient." Arch Intern Med, 146, p. 969-73
  7. Watson WA (1987) "Factors influencing the clinical efficacy of activated charcoal." Drug Intell Clin Pharm, 21, p. 160-6
  8. Kivisto KT, Neuvonen PJ (1990) "The effect of cholestyramine and activated charcoal on glipizide absorption." Br J Clin Pharmacol, 30, p. 733-6
  9. Dolgin JG, Nix DE, Sanchez J, Watson WA (1991) "Pharmacokinetic simulation of the effect of multiple-dose activated charcoal in phenytoin poisoning: report of two pediatric cases." DICP, 25, p. 646-9
  10. Rowden AM, Spoor JE, Bertino JS, Jr (1990) "The effect of activated charcoal on phenytoin pharmacokinetics." Ann Emerg Med, 19, p. 1144-7
  11. Farrar HC, Herold DA, Reed MD (1993) "Acute valproic acid intoxication: enhanced drug clearance with oral-activated charcoal." Crit Care Med, 21, p. 299-301
  12. Howard CE, Roberts RS, Ely DS, Moye RA (1994) "Use of multiple-dose activated charcoal in phenytoin toxicity." Ann Pharmacother, 28, p. 201-3
  13. Chernish SM, Wolen RL, Rodda BE (1972) "Adsorption of propoxyphene hydrochloride by activated charcoal." Clin Toxicol, 5, p. 317-29
  14. Glab WN, Corby DG, Decker WJ, Coldiron VR (1982) "Decreased absorption of propoxyphene by activated charcoal." J Toxicol Clin Toxicol, 19, p. 129-38
  15. Karkkainen S, Neuvonen PJ (1985) "Effect of oral charcoal and urine pH on dextropropoxyphene pharmacokinetics." Int J Clin Pharmacol Ther Toxicol, 23, p. 219-25
  16. Wakabayashi Y, Maruyama S, Hachimura K, Ohwada T (1994) "Activated charcoal interrupts enteroenteric circulation of phenobarbital." J Toxicol Clin Toxicol, 32, p. 419-24
  17. Reed MD (1988) "Oral activated charcoal therapy." Am J Emerg Med, 6, p. 318
  18. Neuvonen PJ (1982) "Clinical pharmacokinetics of oral activated charcoal in acute intoxications." Clin Pharmacokinet, 7, p. 465-89
  19. Naveau S, Bonhomme L, Preaux N, Chaput JC (1991) "A pure charcoal suspension for colonoscopic tattoo." Gastrointest Endosc, 37, p. 624-5
  20. Ilkhanipour K, Yealy DM, Krenzelok EP (1993) "Activated charcoal surface area and its role in multiple-dose charcoal therapy." Am J Emerg Med, 11, p. 583-5
  21. Saetta JP (1993) "Gastric decontaminating procedures: is it time to call a stop?" J R Soc Med, 86, p. 396-9
  22. Orisakwe OE (1994) "Activated charcoal: is failure to use it negligence or ignorance?" South Med J, 87, p. 165-8
  23. Herrington AM, Clifton GD (1995) "Toxicology and management of acute drug ingestions in adults." Pharmacotherapy, 15, p. 182-200
  24. Bonuccelli U, Piccini P, Del Dotto P, Pavese N, D'Antonio P, Muratorio A (1992) "Apomorphine test in de novo Parkinson's disease." Funct Neurol, 7, p. 295-8
  25. (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
View all 25 references

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Moderate

acetaminophen butalbital

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine) and Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine)

MONITOR: Barbiturates may increase the hepatotoxic potential of acetaminophen and decrease its therapeutic effects. The mechanism may be related to accelerated CYP450 metabolism of acetaminophen with consequent increase in hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose.

MANAGEMENT: Monitoring for altered efficacy and safety is recommended. Prolonged use or high doses of acetaminophen should be avoided by patients on barbiturate therapy.

References

  1. Pirotte JH (1984) "Apparent potentiation by phenobarbital of hepatotoxicity from small doses of acetaminophen." Ann Intern Med, 101, p. 403
  2. Douidar SM, Ahmed AE (1987) "A novel mechanism for the enhancement of acetaminophen hepatotoxicity by phenobarbital." J Pharmacol Exp Ther, 240, p. 578-83
  3. Wright N, Prescott LF (1973) "Potentiation by previous drug therapy of hepatotoxicity following paracetamol overdose." Scott Med J, 18, p. 56-8
  4. Bock KW, Wiltfang J, Blume R, Ullrich D, Bircher J (1987) "Paracetamol as a test drug to determine glucuronide formation in man: effects of inducers and of smoking." Eur J Clin Pharmacol, 31, p. 677-83
View all 4 references

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Drug and food interactions

Major

acetaminophen food

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine)

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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Major

butalbital food

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 references

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Moderate

codeine food

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
View all 9 references

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Minor

caffeine food

Applies to: Phrenilin with Caffeine and Codeine (acetaminophen / butalbital / caffeine / codeine)

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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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.