Reglan with Benadryl for Worsening Nausea and Dry Heaving
Yes, Reglan (metoclopramide) remains effective for nausea and dry heaving when combined with Benadryl (diphenhydramine), and this combination is specifically supported for managing nausea with the added benefit that Benadryl helps prevent metoclopramide's extrapyramidal side effects. 1
Efficacy of the Combination
Metoclopramide is effective as monotherapy for nausea and vomiting, with documented use in multiple clinical settings including diabetic gastroparesis, chemotherapy-induced nausea, and postoperative nausea 1
The combination of metoclopramide plus diphenhydramine has been specifically studied and shown to be effective for severe nausea and vomiting, particularly in hyperemesis gravidarum where it demonstrated 36% improvement in vomiting symptoms 2
Diphenhydramine does not reduce metoclopramide's antiemetic efficacy - while one study in cancer chemotherapy patients found diphenhydramine didn't add additional antiemetic benefit, it also didn't interfere with metoclopramide's effectiveness 3
Safety Profile and Extrapyramidal Protection
The FDA label specifically recommends diphenhydramine 50 mg IM for acute dystonic reactions that may occur with metoclopramide, stating "symptoms usually will subside" 1
Diphenhydramine provides some protection against extrapyramidal side effects, though it does not give absolute protection - this is an important caveat as patients can still develop dystonic reactions even with concurrent diphenhydramine use 3
Metoclopramide carries risk of tardive dyskinesia with chronic use, which is why the National Comprehensive Cancer Network guidelines note that chronic metoclopramide use may be limited due to concern for neurologic complications 4
Dosing Considerations
Standard metoclopramide dosing for nausea is 10 mg orally or IV, administered 20-30 minutes before meals or with other antiemetics 4
For severe or refractory nausea, metoclopramide can be dosed up to 60 mg/day orally in divided doses, as demonstrated in studies of chronic nausea in advanced cancer 5
Diphenhydramine is typically dosed at 25-50 mg every 6 hours when used prophylactically with metoclopramide 2
Important Caveats and Monitoring
If nausea is worsening despite metoclopramide, consider alternative causes including constipation (which metoclopramide can help via prokinetic effects), CNS pathology, hypercalcemia, or medication side effects 4
Metoclopramide should be limited to short-term use when possible - one case report documented severe, long-lasting adverse effects (anxiety, depression, involuntary movements) lasting 10 months after only 40 mg total dose over several days 6
For breakthrough nausea on metoclopramide, add an agent from a different drug class rather than increasing the metoclopramide dose - options include 5-HT3 antagonists (ondansetron, granisetron), phenothiazines (prochlorperazine), or haloperidol 4, 7
Renal impairment requires dose adjustment - for creatinine clearance below 40 mL/min, initiate metoclopramide at approximately half the recommended dosage 1
When to Escalate Therapy
If nausea persists beyond one week on metoclopramide plus diphenhydramine, reassess the underlying cause and consider adding or switching to alternative antiemetics 4
Combination therapy with metoclopramide plus a 5-HT3 antagonist or corticosteroid may be more effective than metoclopramide alone for refractory cases 4
Alternative first-line agents if metoclopramide fails include granisetron (particularly transdermal formulation), prochlorperazine, or haloperidol 7