Acetaminophen, caffeine, and dihydrocodeine

Name: Acetaminophen, caffeine, and dihydrocodeine

Acetaminophen, caffeine, and dihydrocodeine side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

In rare cases, acetaminophen may cause a severe skin reaction that can be fatal. This could occur even if you have taken acetaminophen in the past and had no reaction. Stop taking this medicine and call your doctor right away if you have skin redness or a rash that spreads and causes blistering and peeling. If you have this type of reaction, you should never again take any medicine that contains acetaminophen.

Like other narcotic medicines, dihydrocodeine can slow your breathing. Death may occur if breathing becomes too weak.

Stop using this medication and call your doctor at once if you have:

  • shallow breathing, slow heartbeat;

  • fast or pounding heart rate, feeling light-headed, fainting;

  • confusion, hallucinations, unusual thoughts or behavior;

  • muscle twitching;

  • problems with urination;

  • infertility, missed menstrual periods;

  • impotence, sexual problems, loss of interest in sex;

  • easy bruising or bleeding;

  • liver problems--nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

  • low cortisol levels-- nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated.

Common side effects include:

  • slowed breathing;

  • dizziness, drowsiness, tired feeling, headache, confusion;

  • nausea, vomiting, stomach pain, constipation, diarrhea;

  • indigestion, loss of appetite;

  • sweating, itching;

  • dry mouth, blurred vision; or

  • little or no urinating;

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Proper Use of acetaminophen, caffeine, and dihydrocodeine

Take acetaminophen, caffeine, and dihydrocodeine 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 acetaminophen, caffeine, and dihydrocodeine is taken for a long time, it may become habit-forming (causing mental or physical dependence) or cause an overdose. Large amounts of acetaminophen may cause liver damage.

acetaminophen, caffeine, and dihydrocodeine should come with a Medication Guide. Read and follow the 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).

Dosing

The dose of acetaminophen, caffeine, and dihydrocodeine 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 acetaminophen, caffeine, and dihydrocodeine. 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—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of acetaminophen, caffeine, and dihydrocodeine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

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.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Remove the medicine from the original container and mix them with used coffee grounds or kitty litter. Place them in a sealable bag, empty can or container to prevent from leaking.

Uses of Acetaminophen, Caffeine, and Dihydrocodeine

  • It is used to ease pain.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Trezix: Acetaminophen 320.5 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg

Trezix: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg [DSC]

Generic: Acetaminophen 320.5 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg

Tablet, Oral: Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine bitartrate 32 mg [DSC]

ALERT U.S. Boxed Warning

Addiction, abuse, and misuse:

Use exposes 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, and monitor all patients regularly for the development of these behaviors and conditions.

Life-threatening respiratory depression:

Serious, life-threatening, or fatal respiratory depression may occur with use. Monitor for respiratory depression, especially during initiation of therapy or following a dose increase.

Accidental ingestion:

Accidental ingestion, especially by children, can result in a fatal overdose of dihydrocodeine.

Neonatal opioid withdrawal syndrome:

Prolonged use of opioids 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.

Death related to ultra-rapid metabolism of codeine to morphine

Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism.

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 dosages that exceed 4,000 mg/day, and often involve more than 1 acetaminophen-containing product.

Cytochrome P450 interaction

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 dihydrocodeine requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.

Cytochrome P450 3A4 interaction: The concomitant use with all CYP 3A4 inhibitors or discontinuation of a CYP 3A4 inducer may result in an increase in codeine plasma concentrations with subsequently greater metabolism by CYP 2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.

The concomitant use with all CYP 3A4 inducers or discontinuation of a CYP 3A4 inhibitor may result in lower codeine levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels. This may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal.

Follow patients receiving acetaminophen/caffeine/dihydrocodeine and any CYP 3A4 inhibitor or inducer for signs and symptoms that may reflect opioid toxicity and opioid withdrawal when acetaminophen/caffeine/dihydrocodeine are used in conjunction with inhibitors and inducers of CYP 3A4.

Cytochrome P450 2D6 interaction: The concomitant use with all CYP 2D6 inhibitors may result in an increase in codeine plasma concentrations and a decrease in the plasma concentration of the active metabolite, morphine, which could result in an analgesic efficacy reduction or symptoms of opioid withdrawal.

The discontinuation of a CYP 2D6 inhibitor may result in a decrease in codeine plasma concentrations and an increase in the plasma concentration of the active metabolite, morphine, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.

Follow patients receiving acetaminophen/caffeine/dihydrocodeine and any CYP 2D6 inhibitor for signs and symptoms that may reflect opioid toxicity and opioid withdrawal when acetaminophen/caffeine/dihydrocodeine are used in conjunction with inhibitors of CYP 2D6.

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 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.

Pregnancy Risk Factor C Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. [US Boxed Warning]: Prolonged use opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated 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. Dihydrocodeine is a semisynthetic analogue of codeine; it has been shown to cause respiratory depression in the fetus when administered to women during labor (Leppert 2010; Myers 1958; Sliom 1970). Also refer to the Acetaminophen and Caffeine individual monographs for additional information.

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