Hydrocodone is often compounded with other generally less effective non-opioid compounds such as paracetamol (also known as acetaminophen) or ibuprofen, both often added to discourage recreational use^{[citation needed]} (as paracetamol can cause potentially fatal liver toxicity at high doses), and to provide a possible synergy of analgesic effects between hydrocodone and the non-opioid compounds present. The particular niche in which hydrocodone is most commonly used is as an intermediate centrally acting analgesic. Abrupt discontinuation of hydrocodone (Vicodin, Vicodin ES, and Norco) may result in withdrawal symptoms.

Because of concerns about liver damage from protracted use of paracetamol at high doses, four pharmaceutical companies (Purdue Frederick, Cephaoln, Zogenix, and Egalet) are developing extended-release capsules and other forms of hydrocodone by itself.

Hydrocodone is used to treat moderate to severe pain and as an antitussive to treat cough.^[6]

Pharmacology

As a narcotic, hydrocodone relieves pain by binding to opioid receptors in the brain and spinal cord. It can be taken with or without food as desired. When taken with alcohol, it can intensify drowsiness. It may interact with monoamine oxidase inhibitors, as well as other drugs that cause drowsiness.

It is in FDA pregnancy category C. Animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. In addition, a newborn of a mother taking the medication may exhibit breathing problems or withdrawal symptoms.

Studies have shown hydrocodone is stronger than codeine but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of hydrocodone was actually found to be higher than that of morphine.^[7] Per os hydrocodone has a MEDD factor of .4, meaning that 1 mg of hydrocodone is equivalent to .4 mg of intravenous morphine. However, because of morphine's low oral bioavailability, there is a 1:1 correspondence between orally administered morphine and orally administered hydrocodone.^[8]

Hydrocodone can be habit-forming, which leads to physical and psychological dependence. The potential for addiction varies from individual to individual depending on unique biological differences. Sales and production of this drug have increased significantly in recent years, as have diversion and illicit use.

In the U.S., formulations containing more than 15 mg per dosage unit are considered Schedule II drugs, as would any formulation consisting of just hydrocodone alone. Those containing less than or equal to 15 mg per dosage unit in combination with paracetamol or another non-controlled drug are called hydrocodone compounds and are considered Schedule III drugs. Hydrocodone is typically found in combination with other drugs such as paracetamol, aspirin, ibuprofen and homatropine methylbromide. The purpose of the non-controlled drugs in combination is often twofold: 1) To provide increased analgesia via drug synergy. 2) To limit the intake of hydrocodone by causing unpleasant and often unsafe side effects at higher-than-prescribed doses.

In the UK, it is listed as a Class A drug under the Misuse of Drugs Act 1971. Hydrocodone is not commercially available in pure form in the United States due to a separate regulation, and is always sold with an NSAID, paracetamol, antihistamine, expectorant, or homatropine. Pure hydrocodone is a more strictly controlled Schedule II drug^[9] and sold by compounding pharmacies. The cough preparation Codiclear DH is the purest commercial US hydrocodone item, containing guaifenesin and small amounts of ethanol as active ingredients. In Germany and elsewhere, hydrocodone is available as single-active-ingredient tablets as Dicodid (by analogy to the original manufacturer's other products Dilaudid and Dinarkon and others) available in 5- and 10-mg strengths.

As with many other opioids, it is quite possible to reduce the amount of hydrocodone needed to stop a certain level of pain by having the patient take the hydrocodone along with one of the medications with analgesic-sparing properties, also known as potentiators. The most common, one of the most effective with hydrocodone, and safest is hydroxyzine (often marketed under the brand name Vistaril). Orphenadrine, nefopam, carisoprodol, and antihistamines also potentiate most opioids. Especially in the case of carisoprodol, it is imperative that the titration and addition of the potentiator be done under strict supervision of a physician.

Hydrocodone also interacts relatively well with most adjuvant and atypical analgesics used for severe and neuropathic pain such as first-generation anti-depressants, anticholinergics, anticonvulsants, centrally acting stimulants, NMDA antagonists, etc. Hydrocodone can usually be successfully used with duloxetine (Cymbalta) for neuropathic pain, especially that from diabetic neuropathy, provided that the patient has normal relative and absolute levels of Cytochrome P450-related liver enzymes.