Synalgos-DC

Name: Synalgos-DC

Warnings

Salicylates should be used with extreme caution in the presence of peptic ulcer or coagulation abnormalities.

Death Related to Ultra-Rapid Metabolism of Codeine to Morphine

Respiratory depression and death have occurred in children who received codeine in the post-operative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine.

Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (gene duplications denoted as *1/*1xN or *1/*2xN). The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. Data are not available for other ethnic groups. These individuals convert dihydrocodeine into its active metabolite, dihydromorphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum dihydromorphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing).

Children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to the respiratory depressant effects of codeine that has been rapidly metabolized to morphine. Synalgos-DC is contraindicated for post-operative pain management in all pediatric patients undergoing tonsillectomy and/or adenoidectomy [see CONTRAINDICATIONS].

When prescribing dihydrocodeine-containing drugs, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of dihydromorphine overdose.

Drug Dependence

Dihydrocodeine can produce drug dependence of the codeine type and therefore has the potential of being abused. Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of dihydrocodeine, and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic-containing medications. Like other narcotic-containing medications, dihydrocodeine is subject to the provisions of the Federal Controlled Substances Act.

Usage in Ambulatory Patients

Dihydrocodeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient using Synalgos-DC should be cautioned accordingly.

Interactions with other Central Nervous System Depressants

Patients receiving other narcotic analgesics, general anesthetics, tranquilizers, sedative-hypnotics, or other CNS depressants (including alcohol) concomitantly with Synalgos-DC may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Usage in Pregnancy

Reproduction studies have not been performed in animals. There is no adequate information on whether this drug may affect fertility in human males and females or has a teratogenic potential or other adverse effect on the fetus.

Usage in Nursing Mothers

Dihydrocodeine bitartrate is secreted into human milk. In women with normal dihydrocodeine metabolism (normal CYP2D6 activity), the amount of dihydrocodeine secreted into human milk is low and dose-dependent. However, some women are ultra-rapid metabolizers of dihydrocodeine. These women achieve higher-than-expected serum levels of dihydrocodeine's active metabolite, dihydromorphine, leading to higher-than-expected levels of dihydromorphine in breast milk and potentially dangerously high serum dihydromorphine levels in their breastfed infants. Therefore, maternal use of dihydrocodeine can potentially lead to serious adverse reactions, including death, in nursing infants.

The risk of infant exposure to dihydrocodeine and dihydromorphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and the baby. Caution should be exercised when dihydrocodeine is administered to a nursing woman. If a dihydrocodeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using dihydrocodeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of dihydrocodeine during breast-feeding [see WARNINGS].

Aspirin and caffeine are also excreted in breast milk in small amounts. Because of the potential for serious adverse reactions in nursing infants from this combination product, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Usage in Children

Preparations containing aspirin should be kept out of the reach of children. Synalgos-DC is not recommended for patients 12 years of age and under. Since there is no experience in children who have received this drug, safety and efficacy in children have not been established.

Respiratory depression and death have occurred in children with obstructive sleep apnea who received codeine in the post-operative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). These children may be particularly sensitive to the respiratory depressant effects of codeine that has been rapidly metabolized to morphine. Synalgos-DC is contraindicated for post-operative pain management in all pediatric patients undergoing tonsillectomy and/or adenoidectomy [see CONTRAINDICATIONS].

What should I discuss with my healthcare provider before taking Synalgos-DC (aspirin, caffeine, and dihydrocodeine)?

Aspirin may cause stomach or intestinal bleeding, which can be fatal. This can occur without warning while you are taking this medicine.

You should not use this medicine if you are allergic to aspirin, caffeine, or dihydrocodeine, or if you have:

  • severe asthma, asthma with runny nose and nasal polyps, or other breathing problems;

  • a blockage in your stomach or intestines;

  • hemophilia; or

  • an allergy to NSAIDs (nonsteroidal anti-inflammatory drugs).

Do not use this medicine if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine.

In some people, codeine (dihydrocodeine) breaks down rapidly in the liver and reaches higher than normal levels in the body. This can cause dangerously slow breathing and may cause death, especially in a child.

This medicine should not be given to a child younger than 12 years old.

Do not give this medicine to anyone younger than 18 years old who recently had surgery to remove the tonsils or adenoids. Do not give this medicine to a teenager with a fever, flu symptoms, or chicken pox.

To make sure aspirin, caffeine, and dihydrocodeine is safe for you, tell your doctor if you have ever had:

  • a bleeding or blood clotting disorder;

  • a stomach disorder, especially an ulcer or bleeding;

  • liver or kidney disease;

  • asthma or other breathing disorder;

  • seizures;

  • a head injury or brain tumor;

  • drug or alcohol addiction; or

  • if you use a sedative like Valium (diazepam, alprazolam, lorazepam, Ativan, Klonopin, Restoril, Tranxene, Versed, Xanax, and others).

If you use dihydrocodeine while you are pregnant, your baby could become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks. Taking aspirin during late pregnancy may cause bleeding in the mother or the baby during delivery.

Do not breast-feed while taking aspirin, caffeine, and dihydrocodeine. This medicine can pass into breast milk and cause drowsiness, bleeding, breathing problems, or death in a nursing baby.

How should I take Synalgos-DC (aspirin, caffeine, and dihydrocodeine)?

Follow all directions on your prescription label. Dihydrocodeine can slow or stop your breathing. Never use this medicine in larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Dihydrocodeine may be habit-forming, even at regular doses. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. MISUSE OF NARCOTIC MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription. Selling or giving away aspirin, caffeine, and dihydrocodeine is against the law.

If you need surgery, tell the surgeon ahead of time that you are using this medicine.

Do not stop using this medicine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using aspirin, caffeine, and dihydrocodeine.

Store at room temperature away from moisture and heat.

Keep track of your medicine. Dihydrocodeine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

What should I avoid while taking Synalgos-DC (aspirin, caffeine, and dihydrocodeine)?

This medication may impair your thinking or reactions. Avoid driving or operating machinery until you know how the medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Do not drink alcohol. Dangerous side effects or death could occur.

Ask a doctor or pharmacist before using any cough, cold, allergy, or pain medication. Many combination medicines contain aspirin or caffeine. Taking certain products together can cause you to get too much of a certain drug.

Uses of Synalgos-DC

  • It is used to ease pain.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Very bad dizziness or passing out.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Noisy breathing.
  • Feeling very sleepy.
  • Feeling confused.
  • Chest pain or pressure or a fast heartbeat.
  • Seizures.
  • Very bad belly pain.
  • Very hard stools (constipation).
  • Feeling very tired or weak.
  • Any unexplained bruising or bleeding.
  • Ringing in ears.
  • Hearing loss.
  • Mood changes.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen if you take Synalgos-DC with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Synalgos-DC, please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Synalgos-DC. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Synalgos-DC (dihydrocodeine, aspirin, and caffeine).

Review Date: October 4, 2017

Contraindications

Synalgos-DC is contraindicated for postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy.

Synalgos-DC is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, or aspirin

Synalgos-DC Dosage and Administration

Dosage should be adjusted according to the severity of the pain and the response of the patient. Synalgos-DC is given orally. The usual adult dose is two capsules every 4 hours as need­ed for pain.

For the Consumer

Applies to aspirin / caffeine / dihydrocodeine: oral capsule

Along with its needed effects, aspirin / caffeine / dihydrocodeine 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 while taking aspirin / caffeine / dihydrocodeine:

More common
  • Lightheadedness

Get emergency help immediately if any of the following symptoms of overdose occur while taking aspirin / caffeine / dihydrocodeine:

Symptoms of overdose
  • Confusion
  • difficult or troubled breathing
  • extreme sleepiness
  • irregular, fast or slow, or shallow breathing
  • pale or blue lips, fingernails, or skin

Some side effects of aspirin / caffeine / dihydrocodeine 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:

More common
  • Difficulty having a bowel movement (stool)
  • dizziness
  • drowsiness
  • itching skin
  • nausea
  • relaxed and calm
  • sleepiness
  • vomiting

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