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Narcotic analgesic combinations are products that contain a narcotic analgesic in combination with at least one other analgesic; for example, hydrocodone and acetaminophen, oxycodone and acetaminophen. Narcotic analgesic combinations should only be used to treat moderate-to-severe pain that is not responsive to other less potent analgesics. An analgesic is the name used to describe a medicine that relieves pain.

Experts believe that narcotic analgesic combinations have been overused, overprescribed, and misused in the past which has resulted in more than two million people in the U.S. alone having a substance misuse disorder involving prescription narcotic analgesics.

Narcotic analgesics work by binding to opioid receptors, which form part of the opioid system responsible for sensing pain and controlling pleasurable and addictive behaviors. Opioid receptors are more abundant in the brain and spinal cord but are also located elsewhere in the body such as the stomach and the lungs. The main opioid receptor that narcotic analgesics bind to is the mu receptor.

The other analgesics, such as acetaminophen or ibuprofen, typically found in narcotic analgesic combinations mainly work by inhibiting enzymes called cyclo-oxygenase (COX) enzymes that produce prostaglandins. Prostaglandins promote inflammation, pain and fever.

Narcotic analgesic combinations relieve acute and chronic severe pain by a dual mechanism of action: binding to opioid receptors and inhibiting COX enzymes. Even though narcotic analgesic combinations are very effective at relieving pain, they also tend to cause addiction, dependence, and tolerance (where increasing dosages are needed to provide the same pain-relieving effect).

What are narcotic analgesic combinations used for?

In the past, narcotic analgesic combinations have been used for all types of pain, which may explain why there are so many people addicted to them today.

The most appropriate use of narcotic analgesic combinations is for the relief of short-term, intense pain, such as that occurring immediately after surgery or due to a medical condition.

Narcotic analgesic combinations are also appropriate for relief of pain due to active cancer treatment, palliative care and end-or life care. However, they should only be considered to treat other types of chronic pain conditions under strict conditions and with close monitoring.

What are the differences between narcotic analgesic combinations?

Narcotic analgesic combinations differ in their ingredients. Some contain two active ingredients, others contain up to four. These ingredients all differ with regards to how they work in the body, how potent they are, and how they absorbed, distributed, metabolized and excreted. See narcotic analgesics for an explanation of the different types of narcotics (opioids) that are available.

Common narcotic analgesic combinations available in the U.S.

Are combination narcotic analgesics safe?

There are serious risks associated with narcotic analgesic combination use including respiratory depression (unusually slow and shallow breathing), opioid-use disorder, and potentially fatal overdose.

Opioid-use disorder is defined as the repeated occurrence of at least two out of 11 specific opioid-associated problems, including using opioids in increased amounts or for longer than intended; continued use despite interference with daily activities; or still using while in hazardous situations. Severe opioid-use disorder is defined as a cluster of 6 or more problems and it can affect people from all educational and socioeconomic backgrounds.

Narcotic analgesic combinations are potentially addictive and the risk of becoming emotionally and physically dependent on them increases the more you take and the longer you take them for. When prescribed by a doctor and used for short periods of time, such as for less than five days for pain relief after surgery, the risk of becoming addicted to them is relatively low.

The number of deaths from opioid overdose continues to rise and legislation has been enacted to restrict the prescribing of opioids. More than 110,000 people died in 2022 because of a drug overdose; many of these deaths involved a prescription narcotic analgesic.

When taken exactly as prescribed by a doctor, for short periods of time, for the relief of severe pain, and under strict monitoring, narcotic analgesic combinations are considered acceptable to use. However, they may still be associated with some severe side effects, despite proper use.

What are the side effects of combination narcotic analgesics?

Narcotic analgesic combinations have many side effects, although people with cancer or terminal illness taking these for the control of persistent pain may become tolerant to some of these side effects.

Drowsiness, sleepiness, or dizziness is common with the narcotic component of narcotic analgesic combinations. This can affect your driving or ability to operate machinery or perform other hazardous tasks. Alcohol may potentiate these effects.

Other commonly reported side effects related to the narcotic component include:

• Constipation
• Breathing difficulty
• Itching or a skin rash
• Loss of appetite
• Low blood pressure
• Miosis (constriction of the pupil of the eye)
• Nausea and vomiting
• Problems with urination
• Shakiness or a tremor
• Slow heartbeat.

Withdrawal symptoms may occur when people who have been taking narcotic analgesic combinations abruptly stop taking them. Symptoms are like having the flu, and may include body aches, chills, depression, diarrhea, goose-bumps, headaches, high blood pressure, insomnia, irritability, a runny nose and sweats. Withdrawal symptoms usually last about a week.

Side effects can also occur due to other ingredients included in the narcotic analgesic combination, for example:

• Acetaminophen: potential for liver damage particularly in people who exceed the recommended dosage, drink more than three alcoholic drinks a day, or with pre-existing liver disease
• Ibuprofen: stomach related side effects (such as indigestion and heartburn) and potential for cardiac-related events although risk with ibuprofen is low
• Aspirin: high risk of stomach-related side effects and may interact with some medicines
• Butalbital: may cause drowsiness, constipation, and is potentially addictive
• Caffeine: may cause constipation, headaches or insomnia.