Cancer pain management: Use of acetaminophen and nonsteroidal antiinflammatory drugs
- Russell K Portenoy, MD
Russell K Portenoy, MD
- Chief Medical Officer
- MJHS Hospice and Palliative Care
- Professor of Neurology and Family and Social Medicine
- Albert Einstein College of Medicine
- Ebtesam Ahmed, PharmD, MS
Ebtesam Ahmed, PharmD, MS
- Associate Clinical Professor
- St. John's University College of Pharmacy
- Clinical Pharmacy Specialist Innovative Institute for Palliative Care
- Yair Y Keilson, MD
Yair Y Keilson, MD
- Adjunct Clinical Assistant Professor of Medicine
- Touro College of Osteopathic Medicine
Opioid therapy is the first-line approach for moderate or severe chronic pain in populations with active cancer. (See "Cancer pain management with opioids: Optimizing analgesia".) However, the comprehensive management of pain in patients with cancer also requires expertise in the use of the nonopioid analgesics, such as acetaminophen (also known as paracetamol), non-steroidal antiinflammatory agents (NSAIDs), and a group of drugs referred to as "adjuvant" analgesics or coanalgesics.
A stepwise approach to management of cancer pain that includes both opioid and nonopioid drugs has been codified in the World Health Organization (WHO) "analgesic ladder" approach to cancer pain management (figure 1) :
●Step 1, which represents mild to moderate cancer-related pain, suggests the use of acetaminophen or an NSAID, possibly combined with an adjuvant drug to provide additional analgesia, treat a side effect, or manage a coexisting symptom. (See "Cancer pain management: Adjuvant analgesics (coanalgesics)".)
●For patients with moderate or severe pain, and for those who do not achieve adequate relief with acetaminophen or a NSAID alone, treatment with a step 2 opioid (conventionally used for moderate pain) or a step 3 opioid (conventionally used for severe pain) is appropriate. On both steps 2 and 3, the use of acetaminophen or an NSAID could be considered, as well as other drugs to enhance analgesia or treat side effects.
The analgesic ladder approach is not an evidence-based guideline, but it provides a framework for the stepwise and systematic approach to managing cancer pain. (See "Cancer pain management: General principles and risk management for patients receiving opioids", section on 'General principles of pain management'.)
- World Health Organization. Cancer pain relief, 2nd, World Health Organization, Geneva 1996.
- Eisenberg E, Berkey CS, Carr DB, et al. Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis. J Clin Oncol 1994; 12:2756.
- McNicol E, Strassels SA, Goudas L, et al. NSAIDS or paracetamol, alone or combined with opioids, for cancer pain. Cochrane Database Syst Rev 2005; :CD005180.
- de Craen AJ, Di Giulio G, Lampe-Schoenmaeckers JE, et al. Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review. BMJ 1996; 313:321.
- Curatolo M, Sveticic G. Drug combinations in pain treatment: a review of the published evidence and a method for finding the optimal combination. Best Pract Res Clin Anaesthesiol 2002; 16:507.
- Chary S, Goughnour BR, Moulin DE, et al. The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain. J Pain Symptom Manage 1994; 9:363.
- Sima L, Fang WX, Wu XM, Li F. Efficacy of oxycodone/paracetamol for patients with bone-cancer pain: a multicenter, randomized, double-blinded, placebo-controlled trial. J Clin Pharm Ther 2012; 37:27.
- Axelsson B, Borup S. Is there an additive analgesic effect of paracetamol at step 3? A double-blind randomized controlled study. Palliat Med 2003; 17:724.
- Stockler M, Vardy J, Pillai A, Warr D. Acetaminophen (paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo-controlled cross-over trial. J Clin Oncol 2004; 22:3389.
- Israel FJ, Parker G, Charles M, Reymond L. Lack of benefit from paracetamol (acetaminophen) for palliative cancer patients requiring high-dose strong opioids: a randomized, double-blind, placebo-controlled, crossover trial. J Pain Symptom Manage 2010; 39:548.
- Cubero DI, del Giglio A. Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study. Support Care Cancer 2010; 18:235.
- Nabal M, Librada S, Redondo MJ, et al. The role of paracetamol and nonsteroidal anti-inflammatory drugs in addition to WHO Step III opioids in the control of pain in advanced cancer. A systematic review of the literature. Palliat Med 2012; 26:305.
- Straube C, Derry S, Jackson KC, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database Syst Rev 2014; :CD006601.
- Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth 2008; 18:915.
- Pickering G, Loriot MA, Libert F, et al. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther 2006; 79:371.
- Twycross R, Pace V, Mihalyo M, Wilcock A. Acetaminophen (paracetamol). J Pain Symptom Manage 2013; 46:747.
- Mattia A, Coluzzi F. What anesthesiologists should know about paracetamol (acetaminophen). Minerva Anestesiol 2009; 75:644.
- www.fda.gov/drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm (Accessed on May 20, 2014).
- FDA Drug Safety Communication available online at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm239955.htm (Accessed on January 14, 2011).
- http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on May 20, 2014).
- http://www.fda.gov/drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm (Accessed on May 21, 2014).
- Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382:769.
- Lanza FL, Chan FK, Quigley EM, Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009; 104:728.
- Lazzaroni M, Porro GB. Management of NSAID-induced gastrointestinal toxicity: focus on proton pump inhibitors. Drugs 2009; 69:51.
- Farkouh ME, Greenberg BP. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol 2009; 103:1227.
- Scheiman JM. Prevention of NSAID-Induced Ulcers. Curr Treat Options Gastroenterol 2008; 11:125.
- Intravenous acetaminophen
- Hepatic toxicity
- NONSTEROIDAL ANTIINFLAMMATORY AGENTS
- Side effects
- - Cardiovascular toxicity
- - Gastrointestinal toxicity
- - Bleeding
- - Nephrotoxicity
- - Hepatotoxicity
- Indications and contraindications
- Improving the therapeutic ratio: choice of drug, dose and use of gastroprotectants
- Intravenous NSAIDs
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS