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Drug Interactions between Contrave and tramadol

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

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Interactions between your drugs

Major

buPROPion traMADol

Applies to: Contrave (bupropion / naltrexone) and tramadol

MONITOR CLOSELY: The risk of seizures may be increased during coadministration of tramadol with any substance that can reduce the seizure threshold, such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. These agents are often individually epileptogenic and may have additive effects when combined. Many of these agents also exhibit CNS- and/or respiratory-depressant effects, which may be enhanced during their concomitant use with tramadol.

MANAGEMENT: Caution is advised if tramadol is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with epilepsy, a history of seizures, or other risk factors for seizures (e.g., head trauma, brain tumor, metabolic disorders, alcohol and drug withdrawal, CNS infections).

References (5)
  1. Rosenstein DL, Nelson JC, Jacobs SC (1993) "Seizures associated with antidepressants: a review." J Clin Psychiatry, 54, p. 289-99
  2. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
  3. Gardiner JS, Blough D, Drinkard CR, et al. (2000) "Tramadol and seizures: a surveillance study in a managed care population." Pharmacotherapy, 20, p. 1423-31
  4. Pisani F, Spina E, Oteri G (1999) "Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice." Epilepsia, 40(Suppl 10), S48-56
  5. (2024) "Product Information. Zunveyl (benzgalantamine)." Alpha Cognition, Inc., SUPPL-1
Major

naltrexone traMADol

Applies to: Contrave (bupropion / naltrexone) and tramadol

CONTRAINDICATED: Naltrexone can antagonize the effects of opioids via competitive inhibition of opioid receptors. Patients receiving naltrexone may not benefit from opioid-containing medications such as cough and cold products, antidiarrheal preparations, and narcotic analgesics. Likewise, patients dependent on opioids may experience withdrawal symptoms when given naltrexone. Following use of naltrexone, patients may have increased sensitivity to opioids.

**Note: This warning does not apply to opioid products that are specifically formulated with naltrexone to deter abuse via snorting or intravenous injection when crushed.**

MANAGEMENT: The use of naltrexone is considered contraindicated in patients receiving opioids or dependent on opioids, including those maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine). Naltrexone should also not be given to patients in acute opioid withdrawal. In an urgent situation when analgesia may be required in a patient who has received full blocking doses of naltrexone, consideration should be given to regional analgesia, conscious sedation with a benzodiazepine, use of non-opioid analgesics, or general anesthesia. If opioid analgesia is required, the amount of opioid needed may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged. A rapidly-acting opioid analgesic that minimizes the duration of respiratory depression is preferred. Clinicians should be aware that reversal of full naltrexone blockade by administration of large doses of opiates can cause histamine release. Therefore, patients may experience non-opioid receptor-mediated effects such as facial swelling, itching, generalized erythema, and bronchoconstriction. Irrespective of the drug chosen to reverse naltrexone blockade, the patient should be monitored closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation.

References (1)
  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals
Moderate

buPROPion naltrexone

Applies to: Contrave (bupropion / naltrexone) and Contrave (bupropion / naltrexone)

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Periodic monitoring of hepatic function is advisable.

References (1)
  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals

Drug and food interactions

Moderate

buPROPion food

Applies to: Contrave (bupropion / naltrexone)

GENERALLY AVOID: Excessive use or abrupt discontinuation of alcohol after chronic ingestion may precipitate seizures in patients receiving bupropion. Additionally, there have been rare postmarketing reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who drank alcohol during treatment with bupropion. According to one forensic report, a patient died after taking large doses of both bupropion and alcohol. It is uncertain whether a drug interaction was involved. Single-dose studies in healthy volunteers given bupropion and alcohol failed to demonstrate either a significant pharmacokinetic or pharmacodynamic interaction.

MANAGEMENT: The manufacturer recommends that alcohol consumption be minimized or avoided during bupropion treatment. The use of bupropion is contraindicated in patients undergoing abrupt discontinuation of alcohol.

References (4)
  1. Posner J, Bye A, Jeal S, Peck AW, Whiteman P (1984) "Alcohol and bupropion pharmacokinetics in healthy male volunteers." Eur J Clin Pharmacol, 26, p. 627-30
  2. Ramcharitar V, Levine BS, Goldberger BA, Caplan YH (1992) "Bupropion and alcohol fatal intoxication: case report." Forensic Sci Int, 56, p. 151-6
  3. Hamilton MJ, Bush MS, Peck AW (1984) "The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man." Eur J Clin Pharmacol, 27, p. 75-80
  4. (2001) "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome
Moderate

traMADol food

Applies to: tramadol

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

naltrexone food

Applies to: Contrave (bupropion / naltrexone)

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Periodic monitoring of hepatic function is advisable.

References (1)
  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals
Moderate

buPROPion food

Applies to: Contrave (bupropion / naltrexone)

MONITOR: Additive or synergistic effects on blood pressure may occur when bupropion is combined with sympathomimetic agents such as nasal decongestants, adrenergic bronchodilators, ophthalmic vasoconstrictors, and systemic vasopressors. Treatment with bupropion can result in elevated blood pressure and hypertension. In clinical practice, hypertension, in some cases severe and requiring acute treatment, has been observed in patients receiving bupropion alone and in combination with nicotine replacement therapy. These events have occurred in both patients with and without evidence of preexisting hypertension. Furthermore, postmarketing cases of hypertensive crisis have been reported during the initial titration phase with bupropion-naltrexone treatment.

MANAGEMENT: Caution is advised when bupropion is used with other drugs that increase dopaminergic or noradrenergic activity due to an increased risk of hypertension. Blood pressure and heart rate should be measured prior to initiating bupropion therapy and monitored at regular intervals consistent with usual clinical practice, particularly in patients with preexisting hypertension. Dose reduction or discontinuation of bupropion should be considered in patients who experience clinically significant and sustained increases in blood pressure or heart rate.

References (4)
  1. (2022) "Product Information. Auvelity (bupropion-dextromethorphan)." Axsome Therapeutics, Inc., 1
  2. (2022) "Product Information. Zyban (bupropion)." GlaxoSmithKline UK Ltd
  3. (2022) "Product Information. Wellbutrin XL (bupropion)." Bausch Health, Canada Inc.
  4. (2021) "Product Information. Contrave (bupropion-naltrexone)." Currax Pharmaceuticals LLC
Moderate

buPROPion food

Applies to: Contrave (bupropion / naltrexone)

MONITOR: The concomitant use of bupropion and nicotine replacement for smoking cessation may increase the risk of hypertension. In a clinical study (n=250), 6.1% of patients who used sustained-release bupropion with nicotine transdermal system developed treatment-emergent hypertension, compared to 2.5% of patients treated with bupropion alone, 1.6% treated with nicotine alone, and 3.1% treated with placebo. Three patients in the bupropion plus nicotine group and one patient in the nicotine-only group discontinued treatment due to hypertension. The majority had evidence of preexisting hypertension.

MANAGEMENT: Blood pressure monitoring is recommended for patients concomitantly using bupropion and nicotine replacement for smoking cessation.

References (1)
  1. (2001) "Product Information. Zyban (bupropion)." Glaxo Wellcome

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

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