Codeine-Aspirin-Caffeine

Dihydrocodeine-Aspirin-Caffeine is a combination medication used to treat moderate to moderately severe pain.

• Dihydrocodeine-Aspirin-Caffeine is available under the following different brand names: Synalgos-DC 

Common side effects of Dihydrocodeine-Aspirin-Caffeine include:

• lightheadedness
• dizziness
• drowsiness
• sedation
• nausea
• vomiting
• constipation
• itching or rash
• other skin reactions
• shaking
• anxiety
• agitation
• sleep problems (insomnia)
• ringing in the ears

Serious side effects of Dihydrocodeine-Aspirin-Caffeine include:

• shallow breathing
• slow heart rate
• fast or pounding heart rate
• muscle twitching
• confusion
• unusual thoughts or behavior,
• black, bloody, or tarry stools
• coughing up blood or vomit that looks like coffee grounds

Rare side effects of Dihydrocodeine-Aspirin-Caffeine include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule: Schedule V

• 16 mg/356.4 mg/30 mg

Moderate-to-severe pain

Adult dosage

• 2 capsules orally every 4 hours or as needed
• Limitations of use
  • Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve therapy for use in patients for whom alternative treatment options [eg, non-opioid analgesics], have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Dihydrocodeine-Aspirin-Caffeine has no noted severe interactions with any other drugs
• Dihydrocodeine-Aspirin-Caffeine has no noted serious interactions with any other drugs
• Dihydrocodeine-Aspirin-Caffeine has no noted moderate interactions with any other drugs
• Dihydrocodeine-Aspirin-Caffeine has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity
• Any situation where opioids are contraindicated including significant respiratory depression (in unmonitored settings or the absence of resuscitation equipment), and acute or severe bronchial asthma or hypercapnia
• Children younger than 12 years
  • Postoperative management in children younger than 18 years following tonsillectomy and/or adenoidectomy
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hemophilia
• Reye’s syndrome
• Known allergy to nonsteroidal anti-inflammatory drugs (NSAIDs)
• Syndrome of asthma, rhinitis, and nasal polyps

Effects of drug abuse

• Overdose
• Death

Short-Term Effects

• See “What Are Side Effects Associated with Using Dihydrocodeine-Aspirin-Caffeine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dihydrocodeine-Aspirin-Caffeine?”

Cautions

• May impair mental/physical abilities required for hazardous tasks (eg, driving, operating machinery)
• May cause respiratory depression; risk is greatest during initiation of therapy or following a dosage increase; monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases; to reduce risk, proper dosing and titration are essential; overestimating; dosage when converting patients from another opioid product can result in fatal overdose with first dose
• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases the risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
• In patients who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitoring such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may also obscure the clinical course in a patient with head injury; avoid therapy in patients with impaired consciousness or coma
• May cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics) monitor for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid use in patients with circulatory shock
• Adrenal insufficiency has been reported with opioid use, more often following greater than one month of use; if adrenal insufficiency is suspected, confirm the diagnosis, and if diagnosed, treat with physiologic replacement doses of corticosteroids; wean the patient off of opioids to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency; information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency
• Contains dihydrocodeine bitartrate, a Schedule III controlled substance; as an opioid, the drug exposes users to risks of addiction, abuse, and misuse; assess each patient's risk for opioid addiction, abuse, or misuse before prescribing the drug, and monitor all patients for the development of addiction behaviors and conditions; reduce risks by prescribing drug in smallest appropriate quantity and advising the patient on proper disposal of unused drug
• Caution in elderly or debilitated patients, or patients with the following conditions: adrenocortical insufficiency (Addison disease), asthma, central nervous system depression or coma, chronic obstructive pulmonary disease, decreased respiratory reserve (including emphysema, severe obesity, cor pulmonale, or kyphoscoliosis), delirium tremens, head injury, hypotension, increased intracranial pressure, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, and toxic psychosis
• Life-threatening respiratory depression and death have occurred in children who received codeine; codeine is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to increased exposure to active metabolite morphine; children younger than 12 years appear to be more susceptible to respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression; many reported cases of death occurred in the postoperative period following tonsillectomy and/or adenoidectomy, and many of children had evidence of being ultra-rapid metabolizers of codeine
• Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
• Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period and inform patients and caregivers about risks and the signs of morphine overdose
• Use opioids with caution with MAOIs
• Gastrointestinal (GI) bleeding; caution in patients with a history of GI bleed, alcoholism, or bleeding disorders
• Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time; this can adversely affect patients with inherited (i.e. hemophilia) or acquired (i.e. liver disease or vitamin K deficiency) bleeding disorders; aspirin is contraindicated in patients with hemophilia; aspirin administered pre-operatively may prolong the bleeding time
• Aspirin may cause premature closure of the fetal ductus arteriosus; avoid use in pregnant women starting at 30 weeks of gestation (third trimester)
• Long-term administration of NSAIDs has resulted in renal papillary necrosis and another renal injury; correct volume status in dehydrated or hypovolemic patients before initiating therapy; monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during therapy; avoid the use of the drug in patients with the advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if used in patients with advanced renal disease, monitor patients for signs of worsening renal function Avoid in severe hepatic impairment
• Caffeine may produce central nervous system/cardiovascular stimulation and GI irritation
• Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye syndrome with concomitant use of aspirin in certain viral illnesses
• Opioid analgesic risk evaluation and mitigation strategy (REMS)
• To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
• Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
• To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint

Pregnancy and Lactation

• Use in LIFE-THREATENING emergencies when no safer drug is available. Avoid aspirin during pregnancy, particularly in the third trimester because of the risk of premature closure of the ductus arteriosus
• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data on pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage
• Labor and delivery
  • Use of codeine during labor may lead to respiratory depression in the neonate; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately before labor when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
• Lactation
  • Codeine and its active metabolite, morphine, are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants; in women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent
  • There is no information on the effects of codeine milk production; because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment
  • Distributed in breast milk in small amounts, caution advised