Hydrocodone

Is hydrocodone safe?

For a few days of pain after surgery or an injury, at the label dose and with no alcohol or sedatives on board, most people take hydrocodone without serious harm. It is still one of the riskier medicines anyone is likely to be prescribed. It can cause addiction at prescribed doses, it slows breathing, and one stray tablet can kill a child. We score it 27, a point above oxycodone and well below codeine and tramadol.

Most US prescriptions are tablets that combine hydrocodone with acetaminophen, sold for years as Vicodin, Norco and Lortab and now mostly as generics. That adds a second risk: liver damage when the daily acetaminophen total climbs too high.

Why hydrocodone was moved to Schedule II

Until 2014, combination products sat in Schedule IIIControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary, the same tier as some anabolic steroids. Doctors could phone in prescriptions and patients could get refills. Hydrocodone became the most prescribed opioid in the country and one of the most diverted.

On 6 October 2014 the DEA moved all hydrocodone combination products to Schedule II. Prescriptions now need to be written or sent electronically, cannot be refilled, and fall under the same controls as oxycodone and morphine. Single-ingredient extended-release versions, Zohydro ER (approved in 2013) and Hysingla ER, were Schedule II from the start.

What the boxed warning covers

Every hydrocodone label carries the opioid class boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary:

• addiction, abuse and misuse, which can lead to overdose and death
• life-threatening slowed breathing, especially when starting or after a dose increase
• fatal accidental ingestion, especially by children
• profound sedation, coma and death when combined with benzodiazepines, alcohol or other sedatives
• withdrawal in newborns after long-term use in pregnancy
• a Risk Evaluation and Mitigation Strategy (REMS) that asks prescribers to complete opioid training and counsel patients
• higher hydrocodone levels with CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary inhibitors

Combination products add a liver warning for acetaminophen, and the oral solution adds one for dosing errors between milligrams and millilitres. In FDA-required studies of people starting long-term Schedule IIControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary opioids, about 1% to 6% newly met criteria for addiction within a year, and about 9% and 22% showed abuse and misuse.

The 325 mg rule and hidden acetaminophen

In January 2011 the FDA told makers of prescription combination painkillers to cap acetaminophen at 325 mg per tablet or capsule, with a deadline of 14 January 2014. Older strengths such as 5/500 and 7.5/750 mg are gone from US pharmacies. The aim was to leave more room before liver damage.

The cap does not remove the risk. Someone taking 6 tablets of 10/325 mg gets 1,950 mg of acetaminophen a day before any Tylenol, cold and flu remedy or sleep aid that also contains it. The label warns that most cases of liver failure involve more than 4,000 mg a day, often from more than one product, and the risk is higher with alcohol or liver disease.

Doses on the label

Tablet strength	Usual dose	Daily maximum
5 mg/325 mg	1 to 2 tablets every 4 to 6 hours as needed	8 tablets
7.5 mg/325 mg or 10 mg/325 mg	1 tablet every 4 to 6 hours as needed	6 tablets
Oral solution, 10 mg/300 mg per 15 mL	11.25 mL every 4 to 6 hours as needed	67.5 mL

The label notes that many acute pain conditions need no more than a few days of an opioid. Extended-release hydrocodone is for severe, long-lasting pain only, and daily doses of 80 mg or more of Hysingla ER are reserved for opioid-tolerant patients. Swallow extended-release tablets whole; crushing or chewing can release a fatal dose. Hydrocodone cough medicines are approved only for adults.

Overdose: what to look for

Signs include pinpoint pupils, extreme sleepiness or being impossible to wake, slow or shallow breathing, snoring-like sounds, and cold, clammy skin. Call 911 or your local emergency number and give naloxone if you have it; repeat it if the person does not respond, because hydrocodone can outlast a single dose. For questions about an accidental ingestion, US Poison Help is 1-800-222-1222.

The label asks prescribers to discuss naloxone with every patient, especially anyone who also takes a sedative, has had an overdose or a substance use disorder, or lives with children. Naloxone nasal spray is sold without a prescription in the US.

Who should be careful

Talk to your doctor or pharmacist before taking hydrocodone if you take a benzodiazepine such as alprazolam, a sleeping pill, gabapentin or pregabalin, or drink regularly; have sleep apnoea, lung, liver or kidney disease; have had a substance use problem; or are pregnant. Keep tablets locked away and get rid of leftovers at a pharmacy take-back point. Do not stop suddenly after weeks of daily use. A low score does not mean you should stop a medicine you have been prescribed; it means the risks deserve a conversation.

How we scored it

Track record (85) is the only strong factor. Dependence (10) and regulatory warnings (10) reflect Schedule IIControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary status and one of the longest boxed warningsBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary on any drug. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary and interactions (20 each) and serious side effects (30) sit in the lowest band; hydrocodone edges oxycodone because the usual tablets are weaker, but the acetaminophen in them adds a liver risk oxycodone alone does not carry.