Acetaminophen, caffeine, and dihydrocodeine (Oral route)
a-seet-a-MIN-oh-fen, KAF-een, dye-hye-droe-KOE-deen bye-TAR-trate
Addiction, Abuse, and Misuse: Acetaminophen/caffeine/dihydrocodeine bitartrate expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing acetaminophen/caffeine/dihydrocodeine bitartrate, and monitor all patients regularly for the development of these behaviors or conditions.Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of acetaminophen/caffeine/dihydrocodeine bitartrate. Monitor for respiratory depression, especially during initiation of acetaminophen/caffeine/dihydrocodeine bitartrate or following a dose increase.Accidental Ingestion: Accidental ingestion of even one dose of acetaminophen/caffeine/dihydrocodeine bitartrate, especially by children, can result in a fatal overdose of acetaminophen/caffeine/dihydrocodeine bitartrate.Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. Acetaminophen/caffeine/dihydrocodeine bitartrate is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of acetaminophen/caffeine/dihydrocodeine bitartrate in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.Neonatal Opioid Withdrawal Syndrome: Prolonged use of acetaminophen/caffeine/dihydrocodeine bitartrate during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.Interactions with Drug Affecting Cytochrome P450 Isoenzymes: The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with acetaminophen/caffeine/dihydrocodeine bitartrate requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product.Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of acetaminophen/caffeine/dihydrocodeine bitartrate and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation .
Uses of This Medicine:
Acetaminophen, caffeine, and dihydrocodeine combination is used to relieve moderate to moderately severe pain.
Acetaminophen is used to relieve pain and reduce fever in patients. It does not become habit-forming when taken for a long time. But acetaminophen may cause other unwanted effects when taken in large doses, including liver damage. Caffeine is a CNS stimulant that is used with pain relievers to increase their effect. It has also been used for migraine headaches. Dihydrocodeine belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain.
When dihydrocodeine is used for a long time or in large doses, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.
This medicine is available only with your doctor's prescription.
Before Using This Medicine:
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of Trezix™ in the pediatric population. It should not be used in children 12 years of age or younger. Safety and efficacy have not been established.
Trezix™ should not be used to relieve pain after surgery removal of tonsils or adenoids in any children. Severe breathing problems and deaths have been reported in some children who received codeine after tonsil or adenoid surgery.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of acetaminophen, caffeine, and dihydrocodeine combination in the elderly. However, elderly patients are more likely to have age-related lung, liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving acetaminophen, caffeine, and dihydrocodeine combination in order to avoid potentially serious side effects.
Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Abiraterone Acetate
- Calcium Oxybate
- Chloral Hydrate
- Eslicarbazepine Acetate
- Gabapentin Enacarbil
- Iobenguane I 131
- Magnesium Oxybate
- Methylene Blue
- Morphine Sulfate Liposome
- Nitrous Oxide
- Opium Alkaloids
- Peginterferon Alfa-2b
- Pneumococcal 13-Valent Vaccine, Diphtheria Conjugate
- Potassium Oxybate
- Sodium Oxybate
- St John's Wort
- Tolonium Chloride
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
- Grapefruit Juice
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
Other medical problems—
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Addison's disease (adrenal gland problem) or
- Alcohol abuse, or history of or
- Brain tumor, history of or
- Breathing or lung problems (eg, COPD, sleep apnea, respiratory depression) or
- Cor pulmonale (serious heart condition) or
- Depression, history of or
- Drug dependence, especially with narcotics, or history of or
- Enlarged prostate (BPH, prostatic hypertrophy) or
- Head injuries, history of or
- Hypothyroidism (an underactive thyroid) or
- Increased pressure in the head or
- Mental health problems, history of or
- Obesity (overweight) or
- Problems with passing urine or
- Weakened physical condition—Use with caution. May increase risk for more serious side effects.
- Hypotension (low blood pressure) or
- Pancreatitis (inflammation of the pancreas) or
- Seizures, history of—Use with caution. May make these conditions worse.
- Kidney disease or
- Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
- Lung breathing problems (eg, asthma, respiratory depression), severe or
- Stomach or bowel blockage (including paralytic ileus)—Should not be used in patients with these conditions.
Proper Use of This Medicine:
Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of this medicine is taken for a long time, it may become habit-forming (causing mental or physical dependence) or cause an overdose. Also, large amounts of acetaminophen may cause liver damage.
This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.
This combination medicine contains acetaminophen (Tylenol®). Carefully check the labels of all other medicines you are using, because they may also contain acetaminophen. It is not safe to use more than 4 grams (4,000 milligrams) of acetaminophen in one day (24 hours), as this may increase the risk for serious liver problems.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (capsules):
- For moderate to severe pain:
- Adults—2 capsules every 4 hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 10 capsules per day.
- Children 12 years of age and older—Use and dose must be determined by your doctor.
- Children younger than 12 years of age—Should not be used in these patients.
- For moderate to severe pain:
If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Drop off any unused narcotic medicine at a drug take-back location right away. If you do not have a drug take-back location near you, flush any unused narcotic medicine down the toilet. Check your local drug store and clinics for take-back locations. You can also check the DEA web site for locations. Here is the link to the FDAsafe disposal of medicines website:www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/ensuringsafeuseofmedicine/safedisposalofmedicines/ucm186187.htm .
Precautions While Using This Medicine:
It is very important that your doctor check your progress while you are using this medicine, especially within the first 24 to 72 hours of treatment. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.
Do not use this medicine if you are using or have used an MAO inhibitor (MAOI) such as isocarboxazid [Marplan®], linezolid [Zyvox®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]) within the past 14 days.
This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants (medicines that can make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics (numbing medicines), including some dental anesthetics. Also, there may be a greater risk of liver damage if you drink 3 or more alcoholic beverages while you are taking acetaminophen. Do not drink alcoholic beverages. Check with your doctor before taking any of these medicines while you are using this medicine.
This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.
If you think you or someone else may have taken an overdose of this medicine, get emergency help at once. Signs of an overdose include: dark urine, difficult or troubled breathing, irregular, fast or slow, or shallow breathing, nausea or vomiting, pain in the upper stomach, pale or blue lips, fingernails, or skin, pinpoint pupils of the eyes, or yellow eyes or skin.
Codeine is changed to morphine in the body. Some people change codeine to morphine more quickly than others. These individuals are called "ultra-rapid metabolizers of codeine". Contact your doctor immediately if you experience extreme sleepiness, confusion, or shallow breathing. These symptoms may indicate that you are an "ultra-rapid metabolizer of codeine". As a result, there is too much morphine in the body and more side effects of morphine than usual. Children may be especially sensitive to this effect. Do not give this medicine to:
- Children younger than 12 years of age.
- Children younger than 18 years of age who have had surgery removal of tonsils or adenoids.
- Children 12 to 18 years of age who have a high risk for breathing problems (eg, obstructive sleep apnea, obesity, lung disease).
If a nursing mother is an ultra-rapid metabolizer of codeine, it could lead to a morphine overdose in the nursing baby and cause very serious side effects.
For nursing mothers taking this medicine:
- Talk to your doctor if you have any questions about taking codeine or about how this medicine may affect your baby.
- Call your doctor if you become extremely tired and have difficulty caring for your baby.
- Your baby should generally nurse every 2 to 3 hours and should not sleep for more than 4 hours at a time.
- Check with your doctor, hospital emergency room, or local emergency services (eg, "call 9-1-1") right away if your baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, difficulty breathing, or limpness. These may be symptoms of an overdose and need immediate medical attention.
Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help. Also, lying down for a while may relieve dizziness or lightheadedness.
This medicine may make you dizzy, drowsy, confused, or disoriented. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.
Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.
Do not change your dose or suddenly stop using this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as convulsions (seizures), hallucinations, stomach or muscle cramps, tremors, or unusual behavior.
Using this medicine while you are pregnant may cause serious unwanted effects, including neonatal withdrawal syndrome in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.
Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.
This medicine may cause serious allergic reactions, including anaphylaxis, or certain skin conditions (Stevens-Johnson syndrome). These reactions can be life-threatening and require immediate medical attention. Call your doctor right away if you have a rash, itching, blistering, peeling, or loosening of the skin, fever or chills, trouble breathing or swallowing, or any swelling of your hands, face, mouth, or throat while you are using this medicine.
Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.
Using too much of this medicine may cause reduced infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children. '
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.
Side Effects of This Medicine:
- More common
- Bleeding gums
- blood in the urine or stools
- bloody, black, or tarry stools
- chest pain
- clay colored stools
- dark urine
- decreased appetite
- high fever
- itching or skin rash
- loss of appetite
- painful or difficult urination
- pale skin
- pinpoint red spots on the skin
- sore throat
- sores, ulcers, or white spots on the lips or in the mouth
- stomach pain or tenderness
- swelling of the feet or lower legs
- swollen glands
- unexplained or unusual bleeding or bruising
- unusual tiredness or weakness
- yellow eyes or skin
- decreased urine output
- difficulty with swallowing
- fast heartbeat
- loss of consciousness
- muscle twitching
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- rapid weight gain
- seeing, hearing, or feeling things that are not there
- swelling of the face, ankles, or hands
- tightness in the chest
- unusual drowsiness, dullness, or feeling of sluggishness
- Incidence not known
- Cold sweats
- darkening of the skin
- decrease in the frequency of urination
- decrease in the urine volume
- difficult or troubled breathing
- difficulty in passing urine (dribbling)
- dizziness, faintness, or lightheadedness when getting up from lying or sitting position
- irregular, fast or slow, or shallow breathing
- overactive reflexes
- pale or blue lips, fingernails, or skin
- poor coordination
- talking or acting with excitement you cannot control
- trembling or shaking
- More common
- Difficulty having a bowel movement
- relaxed and calm feeling
- Incidence not known
- Constricted, pinpoint, or small pupils (black part of the eye)
- dry mouth
- gas in the stomach
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Last Updated: 10/6/2020