What to Know About Tylenol #3 (Acetaminophen and Codeine)

Prescription combination analgesic used to treat breakthrough pain

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Tylenol #3 is an oral prescription drug used to relieve mild to moderately severe pain. It contains two active ingredients: 

  • The non-opioid painkiller acetaminophen
  • The opioid painkiller codeine

Tylenol #3 is also known as Tylenol with codeine. It is used in adults and children 12 and over when other painkillers aren't effective.

There is a risk of addiction and abuse with Tylenol #3. This is why it should be used with caution.

This article looks at Tylenol #3, its uses, and dosage. It also discusses some of the side effects and precautions you should take when using this medicine.

Man taking pill medication

Paul Bradbury / Getty Images

Tylenol #3 is also sold under a variety of brand names, such as:

  • APAP-Codeine
  • Capital with Codeine
  • Pyregesic-C
  • Vopac

What Is Tylenol #3 Used For?

Tylenol #3 is a narcotic-analgesic combination. The term narcotic refers to opiates and opioids. Opiates are drugs made from opium, such as morphine. Opioids are drugs like codeine, which have opiate-like effects. An analgesic is any drug designed to relieve pain.

Tylenol #3 is rarely, if ever, the first choice for treating pain. It is usually only considered if there is breakthrough pain. Breakthrough pain is pain that isn't helped by over-the-counter painkillers such as:

Tylenol #3 may also be considered if non-opioid pain relievers are causing intolerable side effects.

Off-Label Use

In the past, health care professionals sometimes used this drug to treat coughs. It was often used for coughs related to an illness like strep throat or for a cough following a surgical procedure such as tonsillectomy.

This practice is frowned upon today. This is because Tylenol #3 comes with a risk of respiratory depression, or abnormally slow and ineffective breathing. The risk is especially high in:

  • Children
  • The elderly
  • People weakened by a medical condition
  • People with severe wasting or cachexia

Recap

Tylenol #3 can be addictive and cause serious side effects. For this reason, it is almost always used to treat pain that hasn't responded to other medications.

Before Taking Tylenol #3

Tylenol #3 is not right for everyone. Because codeine is an opioid drug, patients may become addicted to it. This kind of addiction can be both physical and mental. Before prescribing this drug, doctors must be sure the benefits outweigh the risks.

To do this, doctors need to evaluate a patient's risk of becoming addicted. Risk factors include:

Doctors should also provide counseling to ensure the drug is used safely.

In the United States, Tylenol #3 is available under a program called the Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS). This program aims to reduce the risk of abuse.

The REMS program applies to manufacturers of drugs that have a high risk of serious side effects. Under REMS, manufacturers have to give healthcare providers compliance education. This helps providers know when the drug is appropriate and when it is not.

A history of substance abuse doesn't necessarily mean you can't use Tylenol #3 if you need it. It just means there is a greater need for counseling and oversight.

People with untreated alcoholism or substance abuse disorder should not use Tylenol #3.

Precautions and Contraindications

There are certain groups that should never use Tylenol #3. This is largely because of codeine's impact on the respiratory system.

Codeine is used in some cough suppressants. It works by decreasing activity in the part of the brain that triggers the cough reflex. In younger children and people with respiratory illnesses, this can cause problems like:

  • Respiratory depression
  • Hypoxia, or low blood oxygen
  • In severe cases, death

Because of this, the FDA says Tylenol #3 should not be used in:

  • Children under 12 years of age
  • Children younger than 18 years after tonsillectomy or adenoidectomy
  • People with pre-existing respiratory depression
  • People with asthma who are not being monitored or who do not have access to resuscitation equipment

Tylenol #3 should also not be used in:

  • People who use monoamine oxidase inhibitor (MAOI) antidepressants
  • People with intestinal blockage
  • People with a known allergy to acetaminophen, codeine, or any other ingredient in the drug

Tylenol #3 should be used with extreme caution during pregnancy. Use during pregnancy can cause neonatal opioid withdrawal syndrome. This condition can be life-threatening to a newborn.

If you need any opioid during pregnancy, weigh the risks and benefits with your doctor. Breastfeeding is not recommended when taking Tylenol #3.

Other Narcotic Analgesic Combinations

Other narcotic analgesic combinations are available to treat breakthrough pain. These drugs also have a risk of addiction. In some cases, the risk of addiction may be greater than it is with Tylenol #3.

These drugs include:

Recap

Tylenol #3 isn't right for people with certain risk factors. This includes a history of substance abuse and mental illness. Medical conditions like respiratory depression and the use of certain other drugs may also exclude you from being able to take Tylenol #3.

Dosage of Tylenol #3

Tylenol #3 is available as a tablet or oral solution.

  • The three tablet formulations contain 300 mg of acetaminophen and either 15mg, 30mg, or 60mg of codeine.
  • The oral solution is offered in one formulation: 120mg of acetaminophen and 12mg of codeine per 5-mL dose.

The recommended dosage for adults:

  • Tablets: 1 to 2 tablets every four hours as needed to treat acute pain
  • Oral solution: 15 mL every four hours as needed

The analgesic effect of Tylenol #3 usually reaches a peak within two hours of taking a dose. It typically lasts between four and six hours.

Modifications

Always take the lowest effective dose. A doctor should determine the dose for children 12 and over. The oral solution can be divided into smaller doses, so it is often used for children who are younger or have a smaller body size. Adolescents and teens may be able to take tablets.

When you first start taking Tylenol #3, your doctor will want to monitor you for 24 to 72 hours. This is to watch out for signs of respiratory depression. If the dose is ever increased, you'll need to be monitored for another 24 to 72 hours.

During this period, your doctor will measure your oxygen saturation levels. This is done with either an arterial blood gas test or pulse oximetry. This is especially important for people with cancer, who often take Tylenol #3 to treat chronic pain.

How to Take and Store

Tylenol #3 can be taken with or without food. The oral solution bottle should be shaken thoroughly before use.

Always measure the oral solution with a medication-measuring device. You can get one from your doctor or pharmacist. Avoid "eyeballing" doses, which can lead to overdosing.

Tylenol #3 tablets or oral solution can be stored at room temperature, between 68 F and 77 F. It's best to keep it in a cool, dry room in its original light-resistant container. Never use a drug past its expiration date. Be sure to keep this medication out of reach of children and pets.

Recap

You should always take the lowest effective dose of Tylenol #3. Your doctor will need to monitor you for a day or two after you start taking this medication.

Side Effects of Tylenol #3

Tylenol #3 can cause a number of side effects. Some are low-grade and tend to resolve on their own without treatment. If you have a severe reaction, you may have to stop taking the drug.

Common

The most common side effects of Tylenol #3 are:

  • Drowsiness
  • Lightheadedness or dizziness
  • Shortness of breath
  • Nausea
  • Vomiting
  • Extreme sweating
  • Dry mouth
  • Headache
  • Constipation

Less common side effects include:

  • Diarrhea
  • Abdominal pain
  • Cramps
  • Fainting
  • Heart palpitations
  • Insomnia
  • Nervousness
  • Fatigue

Adrenal insufficiency can develop when opioids are used for longer than one month. This is a condition where adrenal gland function is reduced. Symptoms include:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Fatigue
  • Weakness
  • Dizziness

If this happens, you'll need to gradually stop taking Tylenol #3. You may also be prescribed oral corticosteroid drugs to support adrenal function.

Recap

Some people have mild side effects when taking Tylenol #3. These may include drowsiness, nausea, headache, and constipation.

Severe

High doses of acetaminophen can cause liver injury, even in healthy adults. Taking 4,000 mg within 24 hours can significantly increase the risk of liver poisoning, also called hepatotoxicity. Damage to the liver can be permanent.

Two tablets of Tylenol #3 every four hours is very close to the daily limit of 3,600 mg. If you drink alcohol while taking acetaminophen, it significantly increases the risk of liver damage.

Signs of acetaminophen-induced hepatotoxicity include:

  • Stomach pain
  • Loss of appetite
  • Nausea
  • Vomiting
  • Fatigue
  • Pale-colored stools
  • Dark-colored urine
  • Jaundice, a yellowing of the eyes and/or skin

In the United States, acetaminophen hepatotoxicity is common. In fact, it's responsible for more than 50% of overdose-related acute liver failures and around 20% of all liver transplants.

On rare occasions, Tylenol #3 has also been known to cause anaphylaxis. This is a potentially life-threatening, whole-body allergic reaction. In most cases, the codeine causes this reaction. It can trigger symptoms within minutes of taking a dose.

When to Call 911

Call 911 or go to the ER if you have any of these symptoms after taking Tylenol #3:

  • Hives or rash
  • Shortness of breath
  • Wheezing
  • Dizziness or fainting
  • Nausea or vomiting
  • Swelling of the face, tongue, or throat

If left untreated, anaphylaxis can lead to shock, coma, asphyxiation, heart or respiratory failure, and even death.

Recap

Severe side effects can include liver poisoning and anaphylaxis. These side effects require immediate treatment.

Warnings and Interactions for Tylenol #3

Tylenol #3 should be used with caution in certain groups. A specialist may need to decide on a case-by-case basis how appropriate the drug is for people with some conditions.

Some people with epilepsy, for example, may have more seizures when taking Tylenol #3. Elderly people with reduced kidney function may also have seizures. Because there is no way to know who might be affected, doctors should monitor those at risk for seizures. If seizures occur or worsen, treatment should be stopped.

Acetaminophen can stress the liver, so people with chronic liver disease should take no more than 2,000 mg per day. Someone with severe liver disease may need to take even less. Even if you don't have liver disease, you should always use the smallest amount of acetaminophen you need.

Interactions

The risk of respiratory depression and death is greater when Tylenol #3 is taken with alcohol or drugs that suppress the central nervous system such as benzodiazepines. These drugs are often taken by people with conditions like:

To avoid this, most doctors will find an alternative to Tylenol #3. If there are no reasonable alternatives, the lowest possible dose should be used for the shortest amount of time. The patient should be kept under constant medical supervision while taking the drug.

Tylenol #3 is broken down in the body by an enzyme called CYP450. This means it can interact with other drugs that are broken down in this way.

When you take Tylenol #3 with one of these other drugs, you may have increases or decreases in the blood concentration of one or both drugs. Decreases mean the drugs won't work as well. Increases can make side effects worse.

With Tylenol #3, any drug interaction that causes a drop in blood concentration can lead to significant and sometimes profound opioid withdrawal symptoms.

Some of the drugs that pose the greatest risk for CYP450 interactions are:

  • Azilect (rasagiline)
  • Emsam (selegiline)
  • MAOI inhibitors
  • Marplan (isocarboxazid)
  • Matulane (procarbazine)
  • Parnate (tranylcypromine)
  • Nardil (phenelzine)
  • ProvayBlue (methylene blue)
  • Selincro (nalmefene)
  • St. John's wort (Hypericum perforatum)
  • Zyvox (linezolid)
  • Vivitrol (naltrexone)
  • Xadago (safinamide)

Because these interactions can be severe, Tylenol #3 should not be used with any of these drugs.

There are literally dozens of other drugs that can interact with Tylenol #3. You may need to adjust the dose of these medications or take them at intervals of one to six hours.

To avoid drug interactions, always let your doctor know about any drugs you're taking. This includes:

  • Prescription drugs
  • Over-the-counter medication
  • Herbal supplements
  • Recreational drugs

Withdrawal

One of the major concerns about the long-term use of Tylenol #3 is the risk of addiction and abuse. Another concern is withdrawal symptoms. These can happen when treatment is suddenly stopped.

Don't stop taking Tylenol #3 abruptly if you've been taking it for a long period of time and are showing signs of opioid dependence. Stopping suddenly can cause side effects like:

  • Nausea
  • Vomiting
  • Diarrhea
  • Sweating
  • Abdominal cramping
  • Agitation
  • Rapid return of pain

To avoid this, your doctor will have you taper off your dose over time. Current guidance from the Centers for Disease Control and Prevention recommends starting with a 10% reduction in dose per week.

If you aren't able to quit Tylenol #3 and have signs of physical or mental dependence, speak with your doctor. A drug treatment program might be able to help you overcome your addiction.

Recap

Tylenol #3 can cause dependency. If you quit taking it suddenly, it can also cause severe withdrawal symptoms. Always make sure you stop taking Tylenol #3 under a doctor's supervision.

Summary

Tylenol #3 is a prescription pain reliever that contains a combination of acetaminophen and codeine. It is typically only used if other pain medications haven't worked.

Tylenol #3 isn't for everyone. It can be addictive and may cause withdrawal symptoms. It may also cause serious side effects like respiratory depression and liver damage.

Tylenol #3 can interact with certain other drugs. Make sure to tell your doctor about any medications you're taking, and always take the smallest effective dose.

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