Common Trade Names: Zohydro ER, Hysingla ER, Hycodan (with homatropine), Robidone, Vicodin (with paracetamol), Vicoprofen (with ibuprofen), Azdone (with aspirin)
Other Names: hydrocodone bitartrate, 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one
Hydrocodone is a Schedule II opioid analgesic indicated for the management of severe pain. Because of its relaxing and analgesic properties, hydrocodone carries a high risk for misuse and abuse. To learn more about hydrocodone addiction and how it may be treated, read on.
A Brief History of Hydrocodone
Hydrocodone was first synthesized in 1920 by German scientists Carl Mannich and Helene Löwenheim. Initially branded as Dicodid, it was first marketed in 1924 by Knoll, a German pharmaceutical company. Dicodid was also US-registered and was marketed in North America. Dicodid was composed of pure hydrocodone and came in 5mg and 10mg tablets.
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In 1943, hydrocodone was granted approval for sale by the US Food and Drug Administration and by Health Canada under the trade name Hycodan. Currently, the US accounts for more than 99% of annual consumption of hydrocodone, as it is not widely available anywhere else. In 2017, hydrocodone was listed as the 118th most prescribed medication, with more than 6 million prescriptions across the country.
At one point, Germany was the second biggest consumer of hydrocodone, next to the US. However, presently, Dicodid is no longer manufactured in Germany.
How Does Hydrocodone Work in the Human Body?
Hydrocodone is an opioid analgesic that works by activating opioid receptors in the central nervous system, enteric plexus of the bowel, and the immune cells and the interstitial cells of Cajal in the gastrointestinal tract. Hydrocodone primarily binds to mu-opioid receptors, but as the plasma drug concentration increases, it also begins to activate delta- and kappa-opioid receptors. Opioids produce their analgesic effects by inhibition of the formation of cyclic adenosine monophosphate (cAMP) and subsequent inhibition of the release of nociceptive neurotransmitters which are responsible for pain sensation.
Hydrocodone is a Schedule II opioid medication. Schedule II medications are known to cause severe physical and psychological dependence, and this is why hydrocodone is only available by prescription. Hydrocode is FDA-approved for the management of severe pain for which non-opioid treatments are inadequate and for pain requiring round-the-clock, long-term treatment. Hydrocodone is also a cough suppressant and may be prescribed for cough in adults.
The use of hydrocodone is contraindicated in patients who have previously exhibited hypersensitivity or allergic reaction to the drug or any of its components; those with significant respiratory depression; those with bronchial asthma; and those with known or suspected gastrointestinal obstruction.
In addition, hydrocodone is listed as a US Boxed Warning. Pregnant patients must receive counseling prior to hydrocodone prescription as hydrocodone is known to cross the placenta and prolonged use during pregnancy may cause neonatal withdrawal syndrome. Hydrocodone use during breastfeeding can also cause neonatal drowsiness, central nervous system depression, and in rare cases, death of the newborn.
How Is Hydrocodone Taken or Administered?
Hydrocodone is available as an oral medication. It comes in extended-release (ER) capsules and tablets and also as an oral solution. Patients are advised not to crush, chew, or dissolve the capsules and tablets as this can result in rapid metabolism and subsequent overdose.
- Hydrocodone should be prescribed only by physicians who are knowledgeable in the use of potent opioids.
- The dosing regimen must be individualized and should take into account the patient’s history of analgesic treatment and risk factors for abuse or misuse.
- Patients must be closely monitored for respiratory depression, especially within the first 24 to 72 hours of therapy.
For Opioid-Naïve Patients
- Zohydro ER
- Initial: 10mg every 12 hours
- A total daily dose greater than 80mg must be reserved for patients with an established tolerance to potent opioids
- Hysingla ER
- Initial: 20mg every 24 hours
- A total daily dose of greater than 80mg must be reserved for patients with an established tolerance to potent opioids
- Zohydro ER: Increase by increments of 10mg every 12 hours every 3 to 7 days as needed to achieve adequate analgesia
- Hysingla ER: Increase by increments of 10-20mg per day every 3 to 5 days as needed to achieve adequate analgesia
- Titrate downward every 2 to 4 days; do not withdraw abruptly
What Are the Immediate and Long-Term Effects of Hydrocodone Use?
In general, hydrocodone is safe and well-tolerated. However, just like any other medications, hydrocodone can be associated with several adverse effects. Some of the most common adverse effects of hydrocodone are:
- Nausea and vomiting
- Abdominal pain
- Increased or decreased blood pressure
- Peripheral edema
- Shortness of breath
- Increased sweating
- Urinary retention
In cases of hydrocodone overdose or toxicity, patients can experience severe respiratory depression which can be fatal. Patients suffering from hepatic or renal impairment are at a greater risk for overdose because of slower drug metabolism and thus must be monitored closely for signs of respiratory depression.
Signs of Hydrocodone Use Disorder
As a Schedule II medication, hydrocodone is known to lead to physical and psychological dependence. It carries a high risk for addiction, abuse, and misuse even at recommended doses. Patients taking hydrocodone must therefore be closely monitored for signs of hydrocodone use disorder.
The 5th Edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) lists four categories of pathological behavioral patterns of criteria for Substance Use Disorders (SUD), including hydrocodone abuse:
- Impaired control
- Social impairment
- Risky use
- Pharmacological indicators (tolerance and withdrawal)
Below are the 11 criteria required for the diagnosis of SUDs:
- Taking hydrocodone in larger amounts or for longer than prescribed
- Wanting to reduce or stop using hydrocodone, but not managing to
- Spending a lot of time getting, using, or recovering from hydrocodone
- Feeling intense cravings for hydrocodone
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- Hydrocodone use causes problems with work, school or family obligations such as poor school performance or failure to meet household responsibilities
- Continued use of hydrocodone despite it causing interpersonal or relationship problems
- Giving up important social and recreational activities because of hydrocodone use
- Repeated use of hydrocodone in dangerous situations, such as while driving a vehicle
- Continuing to use hydrocodone despite exacerbation of physical and psychological problems
- Needing a higher dose of hydrocodone to achieve the desired effects (tolerance)
- Development of symptoms after withdrawing from hydrocodone use (withdrawal)
Rehab and Treatment for Hydrocodone Use Disorder
Currently, there are three FDA-approved medications for the treatment of opioid dependence, including that of hydrocodone: methadone, buprenorphine, and naltrexone.
Like hydrocodone, methadone is an opioid analgesic. It is widely used as a maintenance medication in the long-term treatment of opioid addiction. Methadone works similar to hydrocodone and produces analgesic effects common among all opioids, including heroin and morphine. Methadone can reverse hydrocodone dependence by acting as a hydrocodone substitute while simultaneously preventing the development of symptoms associated with hydrocodone withdrawal.
Methadone must be used with great caution as it is potentially fatal in supratherapeutic doses. Methadone has been found to be linked with liver dysfunction, especially when used in conjunction with benzodiazepines and alcohol. Methadone therapy must therefore be done under close supervision, or if possible, under direct observation at accredited clinics. Take-home privileges can only be given once the patient is stable and adherence to therapy can be guaranteed.
Buprenorphine is also an opioid analgesic. By binding to opioid receptors, buprenorphine can produce analgesic and relaxing effects similar to that of hydrocodone, but with significantly less risk for addiction. Thus, buprenorphine can be used as a safe alternative to hydrocodone. Buprenorphine is also relatively safer in supratherapeutic doses as it does not easily lead to respiratory depression.
Buprenorphine can be taken in an outpatient, office-based setting. Studies have shown that using buprenorphine with naloxone increases its effectiveness in treating hydrocodone addiction and further reduces its abuse potential.
In contrast to methadone and buprenorphine, naltrexone is an opioid antagonist. It is often used for relapse prevention in hydrocodone dependence. Naltrexone inhibits dopamine release, thereby reducing the euphoric effects of hydrocodone – the properties that make it addictive. Patients who are on naltrexone therapy will therefore find it more difficult to “get high,” resulting in less relapse episodes and reduced cravings. Naltrexone has also been found to have a very low abuse potential and zero risk for toxicity.
Levo-alpha Acetyl Methadol (LAAM)
LAAM is a synthetic opioid. While it is not FDA-approved for the treatment of opioid dependence, its efficacy and effectiveness is almost comparable to that of methadone, making it a great alternative for patients who cannot tolerate methadone therapy. In addition, LAAM requires less frequent dosing compared to methadone.
There are also psychosocial and behavioral interventions that can be instituted to further support recovery from hydrocodone addiction while in the care of a rehabilitation facility. Some of the most well-studied strategies are counselling and psychotherapy. Combination therapy using both medical and non-medical interventions has been shown to be highly effective in treating opioid dependence, compared to monotherapy alone.
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