What are alternative medications to acetaminophen (Tylenol) other than Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

From the Guidelines

Alternative medications that can replace Tylenol besides NSAIDs include anticonvulsants, such as gabapentin and pregabalin, which have strong evidence for their analgesic effects. These medications are considered first-line treatments for neuropathic pain and are also approved for fibromyalgia, as noted in the study published in the Annual Review of Medicine 1.

Key Points to Consider

• Anticonvulsants like gabapentin and pregabalin exert analgesic effects by binding to calcium channels in the brain and spinal cord, inhibiting the release of excitatory neurotransmitters implicated in pain 1.
• The most bothersome side effects of gabapentin and pregabalin are somnolence, dizziness, and weight gain, which should be carefully considered when prescribing these medications 1.
• Other alternatives, such as topical analgesics (e.g., lidocaine, capsaicin) and certain antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), may also be effective for managing pain, but their use should be tailored to the individual patient's needs and medical history 1.

Important Considerations

• The US Food and Drug Administration (FDA) has approved nonopioid medications for treating chronic pain, including cyclooxygenase inhibitors, amine uptake inhibitors, and calcium channel blockers, but these medications also have clinical limitations, including partial efficacy and side effects 1.
• The relative efficacy of analgesics can be evaluated by comparing the number needed to treat (NNT) to achieve moderate benefit, with anticonvulsants and amine uptake inhibitors having an NNT of 6-7 for neuropathic pain 1.
• Complementary and alternative medical treatments, such as physical therapy, exercise, stress management, and cognitive behavioral therapy, may also be beneficial for managing pain and should be considered as part of a comprehensive treatment plan 1.

From the FDA Drug Label

Tramadol hydrochloride has been studied in three long-term controlled trials involving a total of 820 patients, with 530 patients receiving tramadol hydrochloride Patients with a variety of chronic painful conditions were studied in double-blind trials of one to three months duration. Average daily doses of approximately 250 mg of tramadol hydrochloride in divided doses were generally comparable to five doses of acetaminophen 300 mg with codeine phosphate 30 mg (TYLENOL with Codeine #3) daily, five doses of aspirin 325 mg with codeine phosphate 30 mg daily, or two to three doses of acetaminophen 500 mg with oxycodone hydrochloride 5 mg (TYLOX® ) daily The alternative medications that can replace Tylenol (other than NSAIDs) are:

• Tramadol: as it has been shown to be comparable to Tylenol with Codeine #3 in terms of pain relief 2
• Acetaminophen with oxycodone: as it has been compared to tramadol in clinical trials and shown to be a viable alternative 2
• Acetaminophen with codeine: as it has been directly compared to tramadol in clinical trials and shown to be a viable alternative 2

From the Research

Alternative Medications to Tylenol

• Tramadol is a reasonable alternative to NSAIDs for analgesia and osteoarthritis 3
• Disease-modifying drugs (DMARDs) can be used as an alternative for rheumatoid arthritis 3
• Topical NSAIDs are recommended for non-low back, musculoskeletal injuries 4
• Muscle relaxants may be useful for acute low back pain 4
• Medications that work on opioid and monoamine receptors (e.g., tramadol, tapentadol) can be used for severe or refractory acute pain 4
• Acetaminophen/opioid or NSAID/opioid combinations can be used for severe or refractory acute pain 4

Considerations for Alternative Medications

• Patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder should use lower doses of acetaminophen 4
• Patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease should use nonselective NSAIDs with caution 4
• Selective cyclooxygenase-2 NSAIDs are a more expensive treatment alternative and can be used to avoid the gastrointestinal adverse effects of nonselective NSAIDs 4
• Oxycodone/acetaminophen resulted in slightly greater pain relief than acetaminophen, but was associated with more medication-related adverse events 5