Alternative Headache Treatments When Acetaminophen and Ibuprofen Are Contraindicated
For patients unable to take acetaminophen and ibuprofen, aspirin 650-1000 mg is the first-line alternative for mild to moderate headaches, while triptans (such as sumatriptan 50-100 mg) should be used for moderate to severe headaches. 1, 2
First-Line Alternatives Based on Headache Severity
For Mild to Moderate Headaches
Aspirin 650-1000 mg is the strongest evidence-based alternative NSAID when ibuprofen is contraindicated, with proven efficacy comparable to acetaminophen for tension-type and migraine headaches 1, 3
Naproxen sodium 500-825 mg provides longer duration of action (up to 6 hours) and can be repeated every 2-6 hours as needed, with maximum 1.5 g per day 2
Diclofenac potassium is another effective NSAID option with strong evidence for first-line use 1
Combination therapy with aspirin, acetaminophen, and caffeine would normally be highly effective, but since acetaminophen is contraindicated in this case, aspirin alone or with caffeine may still provide benefit 4
For Moderate to Severe Headaches
Triptans are second-line therapy when over-the-counter analgesics provide inadequate relief, with sumatriptan 50-100 mg showing 61-62% of patients achieving headache response at 2 hours 1, 5
All triptans have well-documented effectiveness, and if one triptan fails, others may still provide relief 1
Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) and fastest onset (15 minutes) for severe attacks, particularly when nausea or vomiting is present 2, 5
Triptans are most effective when taken early in an attack while headache is still mild 1
Parenteral Options for Severe Headaches
When oral medications are insufficient or contraindicated:
IV metoclopramide 10 mg plus IV ketorolac 30 mg is the first-line combination for severe migraine requiring intravenous treatment, providing both direct analgesic effects and synergistic pain relief 2
Ketorolac 30-60 mg IM/IV alone is effective as a parenteral NSAID with rapid onset and 6-hour duration, though it should be used cautiously in patients with renal impairment or GI bleeding history 2
Prochlorperazine 10 mg IV effectively relieves headache pain and is comparable to metoclopramide in efficacy 2
Dihydroergotamine (DHE) has good evidence for efficacy and safety as monotherapy for acute migraine attacks 2
Critical Medication Overuse Warning
Limit all acute headache treatments to no more than 2 days per week to prevent medication-overuse headache, which can lead to daily chronic headaches 1, 2
If headaches occur more frequently than twice weekly, preventive therapy should be initiated rather than increasing acute medication frequency 1, 6
Important Contraindications and Cautions
For Aspirin and NSAIDs:
- Avoid in patients with aspirin/NSAID-induced asthma, active GI bleeding, or severe renal impairment (creatinine clearance <30 mL/min) 2
For Triptans:
Contraindicated in patients with ischemic heart disease, previous myocardial infarction, uncontrolled hypertension, stroke, TIA, or hemiplegic/basilar migraine 5
Perform cardiovascular evaluation in triptan-naive patients with multiple cardiovascular risk factors before prescribing 5
Do not use within 24 hours of ergotamines or other triptans 5
Adjunctive Therapies
Antiemetics (metoclopramide 10 mg or prochlorperazine 25 mg) given 20-30 minutes before analgesics provide synergistic analgesia and improve outcomes 2
Caffeine enhances absorption and efficacy of analgesics when used in combination therapy 2
Medications to Avoid
Opioids (including hydromorphone) should be reserved only for cases where other medications cannot be used, when sedation is not a concern, and when abuse risk has been addressed, as they lead to dependency, rebound headaches, and loss of efficacy 2
Butalbital-containing compounds have questionable efficacy and high risk of medication-overuse headache 2, 7