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Hydrocodone: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Aug 29, 2022.

1. How it works

  • Hydrocodone is an analgesic (pain-reliever) that may be given to treat moderate-to-severe pain that is unresponsive to other, less potent, pain-relieving medicines.
  • Hydrocodone works on receptors in the brain and spinal cord to relieve pain. It is a full opioid agonist that is relatively selective for the mu-opioid receptor, although it can act on other receptors at higher dosages. Like all full agonists, there is no ceiling effect for analgesia but the risk of side effects such as respiratory and CNS depression are more likely at higher dosages. Precisely how hydrocodone relieves pain is unknown, but it is thought to release naturally present opioid-like compounds. When used to treat cough hydrocodone is thought to act on the central cough reflex.
  • Hydrocodone belongs to the group of medicines known as narcotic analgesics. It may also be called an opioid analgesic.

2. Upsides

  • Relieves moderate-to-severe acute and chronic pain not controlled by other pain-relieving medicines.
  • Hydrocodone (by itself) is only available in abuse-deterrent, branded, extended-release forms, under the brand names: Hysingla ER, Vantrela ER, and Zohydro ER.
  • Less potential for constipation, nausea, and vomiting than morphine. However, hydrocodone may be more constipating than oxycodone.
  • May be prescribed with naloxone for those at increased risk of opiate overdosage or who have household members, including children, at risk of accidental ingestion or overdosage.
  • Hydrocodone is available in combination with other medications, for example, hydrocodone and acetaminophen, and hydrocodone and ibuprofen. Generic formulations of these combination medications are available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Drowsiness or dizziness that may impair reaction skills and affect a person's ability to drive or operate machinery. Avoid alcohol.
  • Constipation, nausea, and vomiting (although may be less likely than morphine to cause these effects).
  • All other around-the-clock opiates should be discontinued before extended-release hydrocodone tablets/capsules are started.
  • The CDC states that primary care physicians should consider risks versus benefits before prescribing dosages greater than 50 mg/day of hydrocodone, and avoid dosages greater than 90 mg/day hydrocodone. Other experts recommend consulting a pain management specialist first before prescribing higher dosages. Higher dosages require more frequent monitoring.
  • Evaluate benefits and harms within 1 to 4 weeks following initiation of therapy or dosage increase.
  • May impair reaction skills and affect a person's ability to drive or operate machinery. Avoid alcohol.
  • Known to cause addiction and dependence and may be misused or sought after by drug addicts. The risk is higher in people with psychiatric disorders. Thoroughly evaluate patients and assess risk factors for misuse, abuse, and addiction. Legitimate supplies of products containing hydrocodone may be sought out by drug seekers. Hydrocodone is one of the most abused opioids in the United States. Risk management strategies include written treatment agreement plans (such as contracts), urine drug testing, and other risk assessment and monitoring tools.
  • Taper and discontinue treatment with hydrocodone if the patient engages in serious or repeated aberrant drug-related behaviors or drug abuse.
  • Abrupt discontinuation of any hydrocodone-containing medication in a person who has become physically dependent on it may lead to a withdrawal syndrome and symptoms such as restlessness, pupil dilation, watery eyes, and a runny nose, sweating, muscle aches, insomnia, irritability, and gastrointestinal complaints. Babies born to mothers who are physically dependent on hydrocodone will also be physically dependent.
  • Rarely, serious, life-threatening, breathing problems may occur. The risk is greater with higher dosages of hydrocodone, in people with pre-existing respiratory disease, in seniors or the frail, or in those taking other medications that cause respiratory depression (such as benzodiazepines).
  • Use a lower initial dosage in people with renal impairment.
  • Interaction or overdosage may also cause serotonin syndrome. Symptoms include mental status changes such as agitation, hallucinations, coma, or delirium; a fast heart rate; dizziness; flushing; muscle tremor or rigidity; and stomach symptoms (including nausea, vomiting, and diarrhea).
  • Children are particularly sensitive to the side effects of hydrocodone. Even one dose can be fatal. Instruct patients to keep all their medicines well out of reach of children and pets.
  • May not be suitable for people with pre-existing respiratory depression or respiratory disease, with seizure disorders or a head injury, people with gastrointestinal obstruction, or recent use of monoamine oxidase inhibitors.
  • Prolonged use of opiates during pregnancy can result in neonatal withdrawal syndrome, which can be life-threatening. Has a low risk of causing birth defects such as heart defects, spina bifida, and gastroschisis. Use in late pregnancy can cause respiratory depression in the newborn. Low concentrations of opiates are reported in breastmilk and either nursing or the drug should be discontinued.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Hydrocodone is a potent pain-relieving medicine; however, its use is limited by its potential for addiction and dependence. It is one of the most misused opioids in the United States.

5. Tips

  • May be taken with or without food because neither the absorption of hydrocodone nor its effects are influenced by food.
  • Do not chew or crush, presoak or attempt to dissolve any type of hydrocodone tablet. Swallow whole with a glass of water.
  • Check which brand of hydrocodone you have been prescribed. Zohydro ER capsules are taken every 12 hours while Hysingla ER tablets are administered once a day. When hydrocodone bitartrate is used to treat cough, the usual dosage is 5mg every 4 to 6 hours as needed.
  • One formulation in particular (Hysingla ER) has been associated with choking and getting stuck in the throat. Do not wet or suck the tablet before taking and swallow whole with a large glass of water.
  • Monitor for breathing difficulties, particularly in the first few days of treatment or with any dosage increase.
  • Available in abuse-deterrent formulations.
  • Withdrawal symptoms (symptoms may include muscle and bone pain, diarrhea, insomnia, vomiting) may occur if long-term hydrocodone is stopped abruptly; discontinue slowly on a doctor's advice.
  • Do NOT drink alcohol while taking this medicine.
  • Keep well out of reach of children; even one accidental dose can be fatal.
  • Constipation caused by hydrocodone may be treated with laxatives; nausea and vomiting may be treated with antiemetics.
  • May lower blood pressure on standing; take your time when going from lying down to standing.
  • The need for continued treatment with hydrocodone should be assessed at regular intervals.
  • Do not take during pregnancy or breastfeeding. Tell your doctor if you inadvertently become pregnant.

6. Response and effectiveness

  • Time to peak after oral administration of Hysingla ER is 6 to 30 hours, Vantrela ER: 8 hours, and Zohydro R: 5 hours.
  • Once absorbed, hydrocodone is metabolized by hepatic enzymes CYP2D6 to hydromorphone which is the major metabolite of hydrocodone and has an approximately 10 to 33 fold higher binding affinity (in some cases as much as a 100-fold higher binding affinity) for the mu receptor than hydrocodone. Other hepatic enzymes are involved in the elimination of metabolized hydrocodone.
  • Because CYP2D6 exhibits genetic polymorphism, there is potentially a wide interindividual variation in the way individuals respond to hydrocodone.
  • One dose of Hysingla ER lasts for 24 hours, whereas one dose of either Vantrela ER or Zohydro ER lasts for 12 hours.

7. Interactions

Medicines that interact with hydrocodone may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with hydrocodone. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with hydrocodone include:

  • antibiotics, such as erythromycin
  • anticholinergics, such as benztropine (may increase risk of urinary retention or severe constipation)
  • antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline). May increase risk of serotonin syndrome
  • antiemetics, such as dolasetron, granisetron, or ondansetron
  • antifungal agents, such as itraconazole and ketoconazole
  • anticonvulsants, such as carbamazepine, lamotrigine, phenytoin, phenobarbital, or primidone
  • antimigraine agents such as sumatriptan
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • aprepitant
  • azelastine
  • any medication that may cause drowsiness, such as amphetamines, benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
  • buprenorphine
  • buspirone
  • cannabidiol
  • cannabis
  • desmopressin
  • dextromethorphan
  • diuretics, such as furosemide
  • fusidic acid
  • gastrointestinal agents, such as metoclopramide
  • HIV medications such as ritonavir
  • kava kava
  • ketoconazole
  • magnesium sulfate
  • mifepristone
  • muscle relaxants, such as cyclobenzaprine
  • naltrexone
  • other medications that are CYP3A4 or CYP2D6 inhibitors or inducers
  • pentazocine
  • rifampin
  • sedative-hypnotic agents such as zolpidem or eszopiclone.

Avoid drinking alcohol or taking illegal or recreational drugs while taking hydrocodone.

Note that this list is not all-inclusive and includes only common medications that may interact with hydrocodone. You should refer to the prescribing information for hydrocodone for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use hydrocodone only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: August 29, 2022.