CODEINE. Tylenol #3 is an oral drug available by prescription that is used to relieve mild to moderately severe pain. It contains two active ingredients: the non-opioid painkiller acetaminophen and the opioid painkiller codeine.
Also known as Tylenol with codeine, Tylenol #3 is used in adults and children 12 and over when other non-opioid painkillers—such as over-the-counter Tylenol or nonsteroidal anti-inflammatory drugs like Advil (ibuprofen) or Aleve (naproxen)—are unable to provide relief.1 Even so, Tylenol #3 is used with caution due to the risk of addiction and abuse.
In addition to the brand name Tylenol #3, this drug is sold under a variety of different brand names, such as APAP-Codeine, Capital with Codeine, Pyregesic-C, Vopac, and others.
Uses Of Codeine
Tylenol #3 is classified as a narcotic-analgesic combination. The term narcotic is used as a reference to opiates (which are drugs, like morphine, made from opium) and opioids (drugs like codeine, which have opiate-like effects). An analgesic is any drug designed to relieve pain.
Tylenol #3 is rarely, if ever, used in the first-line treatment of pain. The drug is generally considered when there is breakthrough pain (pain that cannot be relieved with over-the-counter analgesics). Tylenol #3 may also be considered if non-opioid pain relievers are causing intolerable side effects.
Off-Label Use Of Codeine
The combination of acetaminophen and codeine has long been used by dentists, surgeons, pediatricians, and family doctors to treat cough associated with illness (such as strep throat) or cough following a surgical procedure (such as tonsillectomy).
The practice is largely frowned upon today due to the risk of respiratory depression (abnormally slow and ineffective breathing). The risk is especially high in children, the elderly, the infirm, or people with severe wasting (cachexia).2
Before Taking Codeine
Tylenol #3 is not appropriate for everyone. As an opioid drug, codeine can cause both physical dependence and mental dependence (addiction). To avoid this, doctors must ensure that the benefits of treatment outweigh the risks.
This includes evaluating whether a patient is at risk of addiction and providing the necessary counseling to ensure that the drug is used safely. Risk factors include a prior history of substance abuse, a family history of substance abuse, or a mental illness (such as major depression).
To reduce the risk of abuse, Tylenol #3 is available in the United States under a restricted-distribution program called the Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) program.3
Under a REMS program, the U.S. Food and Drug Administration (FDA) requires manufacturers of drugs with a high risk of serious side effects to provide compliance education to health care providers so that they know when the drug is appropriate and when it is not.
Having a history of substance abuse doesn’t automatically exclude you from using Tylenol #3 when medically appropriate. It simply indicates a greater need for pre-treatment counseling and medical oversight.
People with untreated alcoholism or substance abuse disorder should not use Tylenol #3.
Precautions and Contraindications
There are certain groups in whom Tylenol #3 should never be used. A great part of the concern is related to the impact of codeine on the respiratory system.
Codeine found in certain cough suppressants works by decreasing activity in the part of the brain that triggers the cough reflex. In younger children and people with respiratory illnesses, this action can lead to respiratory depression, hypoxia (low blood oxygen), and, in severe cases, death.4
Due to the risk of these potentially life-threatening side effects, the FDA contraindicates the use of Tylenol #3 in:
- Children under 12 years of age
- Children younger than 18 years following tonsillectomy or adenoidectomy
- Persons with pre-existing respiratory depression
- People with acute or severe bronchial asthma whose condition is not being monitored or who do not have access to resuscitation equipment
- Those who use monoamine oxidase inhibitor (MAOI) antidepressants (due to the risk of serotonin syndrome)
- Persons with intestinal blockage in whom codeine may further impair gut motility (peristalsis)
- People with a known allergy to acetaminophen, codeine, or any other ingredient in the drug
While not contraindicated for use, Tylenol #3 should be used with extreme caution during pregnancy. Doing so may cause neonatal opioid withdrawal syndrome, a condition that can be life-threatening to a newborn.
If an opioid of any ort is needed during pregnancy, it is important to speak with your doctor to fully weigh the benefits and risks. Breastfeeding is not recommended when taking Tylenol #3.1
Other Narcotic Analgesic Combinations
Other narcotic analgesic combinations can be used to treat breakthrough pain, although the risk of addiction is generally no less and in some cases greater than with Tylenol #3. These include:
- Ascomp with codeine (butalbital, aspirin, caffeine, and codeine phosphate capsule)
- Ibudone (ibuprofen and hydrocodone)
- Lorcet (acetaminophen and hydrocodone)
- Magnacet (acetaminophen and oxycodone)
- Percodan (aspirin and oxycodone)
Dosage Of Codeine
Tylenol #3 is available as a tablet or as an oral solution.
- The three tablet formulations contain 300 milligrams (mg) of acetaminophen combined with either 15 mg, 30 mg, or 60 mg of codeine.
- The oral solution is offered in one formulation: 120 mg of acetaminophen and 12 mg of codeine per 5-milliliter (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.
Generally speaking, the analgesic effect of Tylenol #3 will reach a peak within two hours of taking a dose and last for between four and six hours.1
Modifications to Codeine
The lowest dose able to deliver pain relief should always be used. For children 12 and over, the dosage is determined by a doctor. Because the oral solution can be divided into smaller doses, it is more commonly used in smaller or younger children. Older adolescents and teens may be able to take tablets.
When first starting treatment, your doctor will want to monitor for signs of respiratory depression for the first 24 to 72 hours (and do the same if the dose is ever increased). This may involve an arterial blood gas test or pulse oximetry to measure oxygen saturation levels.6 This is especially important for people with cancer, who are often prescribed the drug to treat chronic pain.
How to Take and Store codeine
Tylenol #3 can be taken with or without food. If taking the oral solution, be sure to shake the bottle thoroughly before use.
Always measure the oral solution with a medication-measuring device, which you can get from your doctor or pharmacist. Avoid “eyeballing” doses, as this can lead to overdosing.
Tylenol #3 tablets or oral solution can be stored at room temperature, between 68 F and 77 F (20 C to 25 C). It is best to keep the medication 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 or pets.
Side Effects Of Codeine
Tylenol #3 can cause a number of side effects related to acetaminophen or codeine. Some are low-grade and tend to resolve on their own without treatment. Others are severe and may require the discontinuation of treatment.
The most common side effects of Tylenol #3 are:1
- Lightheadedness or dizziness
- Shortness of breath
- Extreme sweating
- Dry mouth
Less commonly, diarrhea, abdominal pain, cramps, fainting, heart palpitations, insomnia, nervousness, and fatigue may occur.
Adrenal insufficiency (reduced adrenal gland function) can develop when opioids are used for longer than one month. Symptoms include nausea, vomiting, loss of appetite, fatigue, weakness, and dizziness. The gradual discontinuation of Tylenol #3 along with the short-term use of oral corticosteroid drugs (to support adrenal function) can usually set things right.7
Even in healthy adults, high doses of acetaminophen can cause liver injury. Taking 4,000 mg within 24 hours can significantly increase the risk of hepatoxicity (liver poisoning) and permanent liver damage.
Taking two tablets of Tylenol #3 every four hours pushes you uncomfortably close to that daily limit (3,600 mg). Drinking alcohol while taking acetaminophen significantly amplifies the risk of liver damage.
Signs of acetaminophen-induced hepatotoxicity include:9
- Stomach pain
- Loss of appetite
- Pale-colored stools
- Dark-colored urine
- Jaundice (yellowing of the eyes and/or skin)
In the United States, acetaminophen hepatotoxicity is 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 a potentially life-threatening, whole-body allergic reaction known as anaphylaxis. In most cases, codeine is the responsible culprit, triggering symptoms within minutes of taking a dose.
When to Call 911
Call 911 or seek emergency care if you experience some or all of the following after taking Tylenol #3:
- Hives or rash
- Shortness of breath
- 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.
Warnings and Interactions
Tylenol #3 should be used with caution in certain groups. The drug may not be contraindicated, per se, but specialist insight may be needed to determine how appropriate the drug is on a case-by-case basis for people with some conditions.
Some people with epilepsy, for example, may experience a greater frequency of seizures when taking Tylenol #3. Elderly people with reduced kidney function may also experience seizures.10 Because there is no way to know who might be affected, doctors should monitor those with a risk of seizures and discontinue treatment if seizures occur or worsen.
Because of the stress acetaminophen can place on the liver, people with chronic liver disease should limit their daily intake to no more than 2,000 mg per day, according to the American College of Gastroenterology, or even less if severe liver disease is present. In addition, even if you don’t have liver disease, always use the smallest amount of acetaminophen possible.11
The risk of respiratory depression and death is greater when Tylenol #3 is taken with benzodiazepines and other drugs (including alcohol) that suppress the central nervous system.
To avoid this, most doctors will simply find alternatives to Tylenol #3. If this is not possible and there are no reasonable alternatives for chronic benzodiazepine users (such as people with generalized anxiety disorder, panic disorder, or agoraphobia), the lowest possible dose should be used for the shortest amount of time under constant medical supervision.