What meds are contraindicated with hydrocodone?

According to the FDA, all opioid medications, including hydrocodone, carry a black box warning against concurrent use with other central nervous system (CNS) depressants due to the heightened risk of serious side effects. It is critical to understand what meds are contraindicated with hydrocodone to prevent life-threatening complications, such as respiratory depression and overdose.

Quick Summary

Dangerous drug interactions with hydrocodone, particularly involving CNS depressants like benzodiazepines and alcohol, can lead to severe sedation and fatal respiratory depression. Combining hydrocodone with MAOIs, SSRIs, and certain medications affecting liver enzymes can also increase toxicity risks. Always consult a healthcare provider regarding medication combinations.

Key Points

• CNS Depressants: Combining hydrocodone with alcohol, benzodiazepines (e.g., Xanax), or muscle relaxants can cause severe respiratory depression, sedation, and death due to synergistic effects.

• MAOIs: Monoamine oxidase inhibitors (MAOIs) and other serotonergic drugs can trigger a potentially fatal condition called serotonin syndrome when mixed with hydrocodone.

• CYP3A4 Interactions: Certain antibiotics, antifungals, and seizure medications can alter how the liver processes hydrocodone, leading to dangerously high or low drug concentrations.

• Naltrexone: This opioid blocker is specifically designed to prevent opioid effects and will cause immediate and severe withdrawal symptoms if taken concurrently with hydrocodone.

• Importance of Disclosure: Always inform your healthcare provider and pharmacist about all medications, supplements, and alcohol consumption to avoid potentially fatal interactions.

Critical Drug Interactions to Avoid with Hydrocodone

Hydrocodone is a potent opioid analgesic used to manage moderate to severe pain. While effective, it carries significant risks, especially when taken with other medications that affect the central nervous system (CNS). The potential for adverse drug interactions can range from increased side effects to life-threatening overdose. This guide provides a detailed overview of the most critical contraindications and interactions to be aware of.

Central Nervous System (CNS) Depressants

Combining hydrocodone with other CNS depressants is one of the most dangerous interactions due to the amplified sedative effects. Both substances slow down brain activity, and their combined effect can be overwhelming, leading to severe respiratory depression, profound sedation, coma, or death.

• Alcohol: This is a major contraindication. Alcohol and hydrocodone both depress the CNS. Even moderate amounts of alcohol can intensify the sedative effects of hydrocodone and dangerously slow or stop breathing. The FDA has issued a black box warning regarding the dangers of this combination.
• Benzodiazepines: These are medications prescribed for anxiety, insomnia, and seizures. Examples include alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan). The co-administration of opioids and benzodiazepines dramatically increases the risk of fatal overdose.
• Muscle Relaxants: Medications such as cyclobenzaprine (Flexeril) and tizanidine (Zanaflex) also depress the CNS. When taken with hydrocodone, they can cause excessive drowsiness and increase the risk of respiratory failure.
• Sedatives and Sleep Aids: Non-benzodiazepine sedatives, often called 'Z-drugs', like zolpidem (Ambien) and eszopiclone (Lunesta) cause drowsiness. Mixing them with hydrocodone can lead to excessive sedation and a higher risk of overdose.
• Other Opioids: Taking hydrocodone with other opioid medications like oxycodone or fentanyl significantly increases the risk of an overdose. The cumulative CNS depression from multiple opioids can overwhelm the body's respiratory system.
• Antihistamines: Many older, first-generation antihistamines, such as diphenhydramine (Benadryl), cause drowsiness and should be avoided in combination with hydrocodone due to additive CNS depressant effects.

Medications Affecting Serotonin Levels

Hydrocodone can have an effect on serotonin levels in the brain, particularly in high doses. Combining it with other drugs that increase serotonin can lead to a potentially life-threatening condition called serotonin syndrome.

• MAOIs (Monoamine Oxidase Inhibitors): This older class of antidepressants is a severe contraindication with hydrocodone. Combining them can lead to a rapid increase in serotonin, resulting in symptoms like high blood pressure, agitation, and seizures. Patients should wait at least 14 days after stopping an MAOI before taking hydrocodone.
• SSRIs and SNRIs: Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac) and serotonin and norepinephrine reuptake inhibitors (SNRIs) like duloxetine (Cymbalta) can also increase serotonin levels. This combination requires careful monitoring by a doctor.
• Other Serotonergic Drugs: Certain other medications, including the opioid tramadol, triptans for migraines, and the herbal supplement St. John's wort, can also increase the risk of serotonin syndrome when combined with hydrocodone.

Drugs Affecting Hydrocodone Metabolism

Hydrocodone is primarily metabolized by liver enzymes, notably CYP3A4. Medications that inhibit or induce these enzymes can dangerously alter hydrocodone levels in the body.

• CYP3A4 Inhibitors: These medications slow down the liver's ability to process hydrocodone, leading to higher concentrations in the bloodstream. This increases the risk of side effects, particularly respiratory depression. Examples include:
  • Certain antibiotics (e.g., erythromycin, clarithromycin)
  • Antifungals (e.g., ketoconazole, itraconazole)
  • HIV medications (e.g., ritonavir)
• CYP3A4 Inducers: These drugs speed up the metabolism of hydrocodone, which can decrease its effectiveness. If a patient becomes dependent and stops taking an inducer, hydrocodone levels could increase sharply, raising the risk of toxicity. Examples include:
  • Certain seizure medications (e.g., carbamazepine, phenytoin, phenobarbital)
  • Antibiotics (e.g., rifampin)
  • Herbal products (e.g., St. John's wort)

Other Notable Interactions

• Naltrexone: This medication is used to block opioid effects in the treatment of opioid use disorder. Taking hydrocodone while on naltrexone can cause sudden and severe opioid withdrawal symptoms.
• Anticholinergics: Combining these medications with hydrocodone can significantly worsen constipation and urinary retention, which are common side effects of opioids.
• Diuretics: Hydrocodone can cause fluid retention, counteracting the effects of diuretics or 'water pills' and potentially raising blood pressure.

Comparison of Risky Drug Classes with Hydrocodone

Drug Class	Mechanism of Interaction	Primary Risk	Examples	Monitoring Needed
CNS Depressants	Additive depressant effects on the brain.	Profound sedation, respiratory depression, coma, and death.	Benzodiazepines (Xanax), alcohol, muscle relaxants (Flexeril), sedatives (Ambien).	Close supervision; avoid concurrent use when possible.
MAOIs	Serotonin syndrome, opioid toxicity.	Potentially fatal serotonin syndrome, high blood pressure, seizures.	Phenelzine (Nardil), selegiline (Emsam).	Strict avoidance; observe a 14-day washout period.
Serotonergic Drugs (SSRIs)	Serotonin syndrome.	Confusion, rapid heart rate, high blood pressure.	Fluoxetine (Prozac), duloxetine (Cymbalta), tramadol.	Careful monitoring and dose adjustments.
CYP3A4 Inhibitors	Increases hydrocodone plasma concentration.	Increased risk of overdose and prolonged adverse effects.	Antibiotics (clarithromycin), antifungals (ketoconazole).	Monitor for increased sedation; consider dose adjustment.
CYP3A4 Inducers	Decreases hydrocodone plasma concentration.	Reduced analgesic effect; withdrawal symptoms if inducer is stopped.	Seizure meds (carbamazepine), St. John's wort, rifampin.	Monitor for reduced effectiveness; adjust dose as needed.
Naltrexone	Blocks opioid receptors.	Precipitates immediate and severe opioid withdrawal.	Naltrexone (Vivitrol).	Avoid concurrent use; specific timing required.

Communication and Safety Measures

Effective communication with your healthcare team is the single most important step to prevent dangerous drug interactions. When being prescribed hydrocodone, always provide a complete list of all medications, including:

• Prescription medications
• Over-the-counter drugs (like cough suppressants or cold remedies)
• Herbal products and dietary supplements (e.g., St. John's wort, tryptophan)
• Vitamins

Your pharmacist is also an excellent resource and can help screen for potential interactions. It's also vital to store hydrocodone and other controlled substances securely, away from children and pets, and to dispose of unused medication properly. For more information on opioid safety, refer to resources from the FDA.

Conclusion

While hydrocodone can be an essential tool for managing pain, it is crucial to recognize its significant interaction risks with other medications. The most serious dangers arise from combining it with other CNS depressants, MAOIs, or substances that significantly alter its metabolism. Proactive communication with healthcare providers and pharmacists, combined with careful adherence to dosing instructions, can help mitigate these risks and ensure the safe and effective use of this medication. In case of a suspected overdose or severe interaction, immediate medical attention is necessary.

Frequently Asked Questions

Can I take Benadryl with hydrocodone?

No, you should not take Benadryl (diphenhydramine) with hydrocodone. Benadryl is an antihistamine that has sedative effects, and combining it with the opioid hydrocodone can dangerously increase drowsiness and the risk of respiratory depression.

What happens if I drink alcohol while on hydrocodone?

Drinking alcohol while on hydrocodone is extremely dangerous. Both are CNS depressants, and their combined effect can cause severe sedation, impaired motor control, slowed breathing, coma, and death. The FDA has issued a boxed warning against this combination.

Why can't I mix hydrocodone with Xanax?

Xanax (alprazolam) is a benzodiazepine and a powerful CNS depressant. Combining it with hydrocodone, another CNS depressant, greatly increases the risk of fatal respiratory depression and overdose. The FDA has mandated a boxed warning for this dangerous combination.

Which antidepressants are contraindicated with hydrocodone?

Monoamine Oxidase Inhibitors (MAOIs) like phenelzine (Nardil) are strictly contraindicated and can cause a life-threatening interaction called serotonin syndrome. Other antidepressants like SSRIs and SNRIs require careful monitoring due to similar risks.

Does St. John's Wort interact with hydrocodone?

Yes, St. John's wort is an herbal supplement that can interact with hydrocodone. It acts as a CYP3A4 inducer, which can decrease hydrocodone's effectiveness. It can also increase serotonin levels, raising the risk of serotonin syndrome.

What should I do if I think someone is overdosing from a hydrocodone interaction?

If you suspect an overdose, administer naloxone (Narcan) if available and immediately call emergency services (911). Signs include pinpoint pupils, unresponsiveness, and slow or shallow breathing. Naloxone can reverse the effects of an opioid overdose and save a life.

Can certain antibiotics or antifungals interact with hydrocodone?

Yes, certain antibiotics (like clarithromycin) and antifungals (like ketoconazole) can inhibit liver enzymes responsible for processing hydrocodone. This can increase hydrocodone levels in the body, leading to a higher risk of side effects and overdose.