Paracetamol + Tramadol Hydrochloride interactions

Food & lifestyle

• alcohol

  Major

  Metabolism

  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.

  What to do: 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).

  12 sources

  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 (2002):

  Show all 12 sourcesShow fewer sources

  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

• alcohol

  Moderate

  Synergy

  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.

  What to do: 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.

  4 sources

  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):

Conditions

Conditions in which Paracetamol + Tramadol Hydrochloride needs care, as documented in this source.

• Alcoholic Intoxication

  Major

  The CNS depressant effects of tramadol may be additive with those of alcohol and may lead to profound sedation, respiratory depression, coma, and death. Therapy with tramadol should be administered cautiously (and only when alternative treatment options are inadequate) in patients who might be prone to acute alcohol intake. Dosages and durations should be limited to the minimum required and patients should be monitored for signs and symptoms of respiratory depression and sedation. Prescribing naloxone for the emergency treatment of opioid overdose should be considered; naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, but it also increases the risk of seizures.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Alcoholism

  Major

  Chronic alcohol abusers may be at increased risk of hepatotoxicity during treatment with acetaminophen (APAP). Severe liver injury, including cases of acute liver failure resulting in liver transplant and death, has been reported in patients using acetaminophen. Therapy with acetaminophen should be administered cautiously, if at all, in patients who consume three or more alcoholic drinks a day. In general, patients should avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure. They should also be advised to seek medical attention if they experience signs and symptoms of liver injury such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.

  11 sources

  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. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  5. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  6. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  7. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):
  8. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50

  Show all 11 sourcesShow fewer sources

  9. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  10. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73

• Intestinal Obstruction

  Major

  Opioid agonists are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

  4 sources

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):
  2. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):
  3. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals (2001):
  4. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):

• Liver Diseases

  Major

  Acetaminophen is primarily metabolized in the liver to inactive forms. However, small quantities are converted by minor pathways to metabolites that can cause hepatotoxicity or methemoglobinemia. Patients with hepatic impairment may be at increased risk of toxicity due to increased minor metabolic pathway activity. Likewise, chronic or overuse of acetaminophen can saturate the primary hepatic enzymes and lead to increased metabolism by minor pathways. Severe liver injury, including cases of acute liver failure resulting in liver transplant and death, has been reported in patients using acetaminophen. Therapy with acetaminophen should be administered cautiously in patients with hepatic insufficiency. Clinical monitoring of hepatic function is recommended. Instruct patients to avoid drinking alcohol while taking acetaminophen-containing medications. Patients should be warned not to exceed the maximum recommended total daily dosage of acetaminophen (4 g/day in adults and children 12 years of age or older), and to read all prescription and over-the-counter medication labels to ensure they are not taking multiple acetaminophen-containing products, or check with a healthcare professional if they are unsure.

  6 sources

  1. Gillette JR "An integrated approach to the study of chemically reactive metabolites of acetaminophen." Arch Intern Med 141 (1981): 375-9
  2. Arnman R, Olsson R "Elimination of paracetamol in chronic liver disease." Acta Hepatogastroenterol (Stuttg) 25 (1978): 283-6
  3. Clements JA, Critchley JA, Prescott LF "The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man." Br J Clin Pharmacol 18 (1984): 481-5
  4. Forrest JA, Adriaenssens P, Finlayson ND, Prescott LF "Paracetamol metabolism in chronic liver disease." Eur J Clin Pharmacol 15 (1979): 427-31
  5. Venkataramanan R, Kalp K, Rabinovitch M, et al. "Conjugative drug metabolism in liver transplant patients." Transplant Proc 21 (1989): 2455
  6. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):

• Respiratory Insufficiency

  Major

  Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Substance-Related Disorders

  Major

  Tramadol exposes patients and other users to the risks of addiction, abuse, and misuse. Each patient's risk should be assessed before prescribing tramadol, and all patients should be monitored regularly for development of such behaviors and conditions. Risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); the potential for such risks should not prevent proper pain management in any given patient. Patients at increased risk may be prescribed tramadol, but use in such patients requires intensive counseling about the risks and proper use of tramadol, as well as intensive monitoring for signs of addiction, abuse, and misuse; prescribing naloxone for the emergency treatment of opioid overdose should be considered.Opioids are sought by drug abusers and patients with addiction disorders and are subject to criminal diversion. These risks should be considered when prescribing or dispensing tramadol. Strategies to reduce such risks include prescribing the smallest appropriate quantity and advising the patient about proper disposal of unused drug.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Depressive Disorder

  Moderate

  Tramadol should not be prescribed for patients who are suicidal or addiction-prone. The use of nonnarcotic analgesics should be considered for patients who are suicidal or depressed. Tramadol should be prescribed with caution for patients with history of misuse and/or are currently taking CNS-active drugs, antidepressant drugs, alcohol in excess, and patients who suffer from emotional disturbance or depression. Patients should be advised not to exceed the recommended dose and to limit their intake of alcohol.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Epilepsy

  Moderate

  Seizures have been reported in patients receiving tramadol within the recommended dosage range. The risk appears to increase with doses above the recommended range and with concomitant use of certain drugs (e.g., those that reduce the seizure threshold). Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (e.g., head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizures.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Gastrointestinal Diseases

  Moderate

  Tramadol may cause spasm of the sphincter of Oddi. Opioids may increase serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be monitored for worsening symptoms.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Hypoglycemia

  Moderate

  Cases of tramadol-associated hypoglycemia have been reported, some resulting in hospitalization. In most cases, patients had predisposing risk factors (e.g., diabetes); caution is recommended in these patients. If hypoglycemia is suspected, blood glucose levels should be monitored and discontinuation of therapy should be considered as appropriate.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Hypotension

  Moderate

  Tramadol may cause severe hypotension (including orthostatic hypotension, syncope) in ambulatory patients. Risk is increased in patients whose ability to maintain blood pressure has already been compromised by reduced blood volume or coadministration of certain CNS depressant drugs; these patients should be monitored for signs of hypotension after starting or titrating tramadol. In patients with circulatory shock, tramadol may cause vasodilation that can further reduce cardiac output and blood pressure; tramadol should be avoided in patients with circulatory shock.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Intracranial Hypertension

  Moderate

  Opioids may obscure the clinical course in a patient with a head injury. The use of tramadol should be avoided in patients with impaired consciousness or coma.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Kidney Diseases

  Moderate

  Tramadol and its metabolites, one of which (referred to as M1) is pharmacologically active and a more potent analgesic than tramadol itself, are primarily excreted in the urine. The rate and extent of excretion of both tramadol and M1 have been shown to decrease in patients with impaired renal function. Therapy with tramadol should be administered cautiously in such patients. In patients with CrCl less than 30 mL/min, dosage reduction is recommended with the immediate-release formulations, while the extended-release formulations should not be used.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Liver Diseases

  Moderate

  Tramadol is converted by the liver to several metabolites, one of which (referred to as M1) is pharmacologically active and a more potent analgesic than tramadol itself. The metabolism of both tramadol and M1 has been shown to decrease in patients with advanced cirrhosis of the liver, resulting in increased exposure to tramadol as well as substantially prolonged elimination half-lives for both tramadol and M1. Therapy with tramadol should be administered cautiously in patients with liver dysfunction. In patients with severe liver dysfunction, dosage reduction is recommended with the immediate-release formulations, while the extended-release formulations should not be used.

  1 source

  1. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001):

• Phenylketonurias

  Moderate

  Several oral acetaminophen and acetaminophen-combination products, particularly flavored chewable tablets, contain the artificial sweetener, aspartame (NutraSweet). Aspartame is converted to phenylalanine in the gastrointestinal tract following ingestion. Chewable and effervescent formulations of acetaminophen products may also contain phenylalanine. The aspartame/phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics).

  1 source

  1. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical (2002):