Can ketorolac be combined with prochlorperazine for the treatment of an acute migraine attack in children?

Ketorolac and Prochlorperazine Combination for Acute Migraine in Children

Prochlorperazine is superior to ketorolac for acute migraine treatment in children, and while they can be combined, there is insufficient evidence to recommend routine combination therapy over monotherapy with prochlorperazine alone. 1, 2

First-Line Treatment Options for Pediatric Migraine

• Ibuprofen is recommended as first-line medication for acute migraine treatment in children at an age-appropriate dose 3
• For adolescents aged 12-17 years, multiple NSAIDs and triptans are approved for acute migraine treatment 3
• For moderate-severe migraines where oral medications are ineffective, IV ketorolac (0.5 mg/kg, maximum 30 mg) may be considered 2

Evidence for Individual Agents

Prochlorperazine

• Prochlorperazine has been shown to be superior to ketorolac in direct comparison studies for pediatric migraine treatment 1
• In one randomized, double-blind trial, 84.8% of children receiving prochlorperazine achieved successful treatment (defined as ≥50% pain reduction) compared to only 55.2% with ketorolac 1
• Among dopamine antagonists, prochlorperazine appears to be the most effective option for pediatric migraine, with lower rates of opioid rescue medication requirements compared to metoclopramide or promethazine 4

Ketorolac

• Ketorolac is commonly used for treating severe migraines in children, with a rapid onset of action and duration of approximately six hours 2
• Unlike chronic use of other analgesics, ketorolac is unlikely to cause rebound headaches when used for acute treatment 2
• However, ketorolac has shown less efficacy than prochlorperazine when used as monotherapy 1, 5

Combination Therapy Considerations

• For patients with accompanying nausea or vomiting, adding an antiemetic such as prochlorperazine to primary analgesic therapy is a reasonable approach 2
• However, a study comparing metoclopramide monotherapy to metoclopramide plus ketorolac found that adding ketorolac did not significantly improve pain scores in children with acute migraine 6
• There is limited direct evidence evaluating the specific combination of ketorolac and prochlorperazine in children, though case reports suggest this combination has been used in clinical practice 7

Practical Treatment Algorithm

1. Start with ibuprofen as first-line therapy for mild-moderate migraine in children 3, 2
2. For adolescents, consider triptans (sumatriptan/naproxen oral, zolmitriptan nasal, sumatriptan nasal, rizatriptan ODT, or almotriptan oral) 8, 2
3. For severe migraines or those with significant nausea/vomiting:
   • Prochlorperazine IV (0.15 mg/kg; maximum 10 mg) appears to be the most effective single agent 1, 4
   • If prochlorperazine alone is insufficient, adding ketorolac may be considered, though evidence for additive benefit is limited 2, 6

Precautions and Contraindications

• Ketorolac is contraindicated in patients with aspirin/NSAID-induced asthma, pregnancy, and cerebrovascular hemorrhage 2
• Potential adverse effects of ketorolac include edema, drowsiness, dizziness, gastrointestinal upset, and increased diaphoresis 2
• Prochlorperazine may cause extrapyramidal symptoms, sedation, and hypotension 4
• Treatment duration with ketorolac should be limited to no more than five days 2

Research Gaps

• There is a need for further well-designed studies for the treatment of pediatric migraine, as highlighted by current guidelines 8
• Most pediatric patients in studies are discharged with residual pain, indicating room for improvement in acute treatment approaches 6