How to manage nausea associated with Hysingla (hydrocodone bitartrate)?

Managing Nausea Associated with Hysingla (Hydrocodone Bitartrate)

For patients experiencing nausea with Hysingla, start metoclopramide 10-20 mg orally every 6 hours as first-line treatment, as it has both central and peripheral antiemetic effects and is specifically recommended for opioid-induced nausea. 1, 2, 3

Initial Assessment

Before treating nausea, rule out the following causes:

• Constipation (the most common overlooked cause of opioid-related nausea) 1
• Central nervous system pathology or brain metastases 1, 2
• Hypercalcemia 1
• Gastroesophageal reflux disease 1, 3
• Other medications contributing to nausea 1, 2
• Electrolyte abnormalities 3

First-Line Treatment Options

Metoclopramide is the preferred first-line agent due to its dual mechanism (dopamine receptor antagonism in the chemoreceptor trigger zone plus prokinetic effects). 1, 2, 3

• Dose: 10-20 mg orally every 6 hours 1, 2, 3
• This is the only FDA-approved medication for gastroparesis-related symptoms 3

Alternative first-line dopamine antagonists if metoclopramide is contraindicated or ineffective:

• Prochlorperazine 10 mg orally every 6 hours as needed 1, 2, 3
• Haloperidol 0.5-1 mg orally every 6-8 hours 1, 2, 3
• Olanzapine 2.5-5 mg orally 1, 2

Prophylactic Strategy

For patients with a prior history of opioid-induced nausea, prescribe antiemetics prophylactically when initiating or increasing Hysingla doses. 1, 2, 3

• Administer metoclopramide or prochlorperazine around-the-clock for the first few days of opioid therapy 1
• Gradually wean the antiemetic as tolerance typically develops within a few days to one week 1, 3

Management of Persistent Nausea

If nausea persists despite as-needed antiemetics:

Switch to scheduled dosing: Administer the antiemetic around-the-clock for 1 week, then transition back to as-needed dosing. 1, 2

Add medications with different mechanisms of action rather than switching between similar agents:

• 5-HT3 receptor antagonists: Ondansetron 8 mg orally once or twice daily, or granisetron orally daily 1, 2, 3
• Corticosteroids: Dexamethasone 2-8 mg orally or IV (particularly effective when combined with metoclopramide and ondansetron) 1, 2, 3
• Anticholinergic agents: Scopolamine transdermal patch 1 mg every 3 days 1, 2, 3
• Antihistamines: Meclizine 12.5-25 mg three times daily 2, 3

Refractory Nausea Management

If nausea persists beyond one week despite the above measures:

1. Reassess the underlying cause of nausea (constipation is frequently missed) 1, 2, 3

2. Consider opioid rotation to a different opioid formulation, as individual patients may tolerate different opioids differently 1, 2

3. Add cannabinoids for refractory symptoms:

   • Dronabinol or nabilone (FDA-approved for chemotherapy-induced nausea, may be considered off-label) 1, 2

4. Consider alternative therapies: Acupuncture, hypnosis, or cognitive behavioral therapy 1, 2, 3

Critical Safety Considerations

Monitor for metoclopramide-related extrapyramidal side effects and tardive dyskinesia, particularly in elderly patients with chronic use. 3

Do not recommend taking Hysingla with food to reduce nausea, as evidence does not support this practice and may actually increase adverse events or alter the abuse-deterrent properties of the formulation. 4

Nausea is among the most common adverse events with Hysingla (reported in clinical trials), along with constipation, vomiting, fatigue, dizziness, somnolence, and headache. 5, 6

Expected Timeline

Tolerance to opioid-induced nausea typically develops within a few days, with most patients experiencing significant reduction in symptoms within one week of stable dosing. 1, 3 If nausea persists beyond this timeframe, aggressive reassessment and escalation of therapy is warranted.