Chlorpheniramine / Codeine

Chlorpheniramine / codeine is a combination medication approved to temporarily relieve cough and upper respiratory symptoms linked to allergy or the common cold.

• Tuxarin ER (extended-release tablet): Approved for adults 18 years and older to temporarily relieve cough and upper respiratory symptoms (such as runny nose or congestion) caused by allergy or the common cold
• This medication is not approved for anyone under 18 years of age — the risks of codeine in younger patients outweigh any benefit
• It is reserved for adults where the benefit of cough suppression clearly outweighs the opioid-related risks, and only after the cause of the cough has been properly evaluated

This medication works through two different ingredients targeting two different problems. Codeine is an opioid that binds to receptors in the brain — specifically at the cough center — to reduce the urge to cough. It is partly converted in the body to morphine, which is thought to be responsible for much of its cough-suppressing effect. Chlorpheniramine is an antihistamine that blocks H1 receptors, stopping histamine from widening blood vessels and causing swelling and excess mucus in the airways — which helps relieve runny nose and other allergy-related symptoms. Chlorpheniramine also has mild sedating and anticholinergic (drying) effects.

Tuxarin ER (extended-release tablet) is taken by mouth. Adults 18 and older take one tablet every 12 hours as needed, and should not exceed two tablets in any 24-hour period. A high-fat meal does not significantly change how the medication is absorbed. Always follow your prescriber's exact instructions — never increase the dose or take it more often than directed, as this raises the risk of serious breathing problems and overdose.

• Do not stop taking it abruptly if you've been on it regularly — your doctor will taper the dose gradually
• If your cough doesn't improve, do not take more; contact your prescriber within 5 days to check for an underlying cause

The most common side effects of Tuxarin ER include:

• Drowsiness, mental clouding, or lethargy
• Dizziness or lightheadedness
• Headache
• Dry mouth
• Nausea or vomiting
• Constipation
• Shortness of breath
• Sweating

More serious reactions — including severely slowed breathing, extreme sleepiness you can't shake, severe low blood pressure, seizures, or signs of allergic reaction (anaphylaxis) — require immediate medical attention. Prolonged use can also affect hormone levels, leading to issues like low libido or irregular periods.

• Life-threatening respiratory depression: Codeine can slow or stop breathing. Risk is greatest when starting the medication, in people with lung disease, in older or frail adults, and when combined with other sedating substances. Seek emergency help immediately if breathing slows significantly.
• Addiction, abuse, and misuse: Codeine is a Schedule III controlled substance. Even at recommended doses, it can cause physical dependence and addiction. Risks are higher in people with a personal or family history of substance use disorder.
• Ultra-rapid codeine metabolism: Some people genetically convert codeine to morphine much faster than usual, reaching dangerously high levels even at normal doses — this can be fatal, especially in children.
• Children: This medication is contraindicated in children under 12 and in anyone under 18 after tonsil or adenoid surgery. Accidental ingestion of even one tablet by a child can be fatal.
• Driving and machinery: This medication causes significant drowsiness and impairs reaction time — avoid driving or operating heavy equipment while taking it.
• Head injuries and increased intracranial pressure: Avoid use in patients with head injuries, as codeine may raise pressure inside the skull and hide signs of worsening injury.
• Seizure disorders: Use with caution; monitor patients with a history of seizures during treatment.

This medication interacts seriously with many common drugs and substances. Always give your pharmacist and prescriber a complete list of everything you take.

• Benzodiazepines and sedatives (e.g., diazepam, alprazolam, sleep aids) — dramatically increase risk of stopped breathing, coma, and death
• Alcohol — intensifies sedation and respiratory depression; avoid completely
• MAO inhibitors (e.g., phenelzine, selegiline, tranylcypromine) — life-threatening reaction; do not use within 14 days of an MAOI
• CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, ritonavir) — raise morphine levels in the blood, increasing overdose risk
• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) — reduce effectiveness and may trigger opioid withdrawal
• CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, bupropion, quinidine) — alter the way codeine is broken down, with unpredictable effects
• Phenytoin — chlorpheniramine may raise phenytoin levels to toxic ranges
• Muscle relaxants — worsen respiratory depression when combined with codeine
• Anticholinergic drugs — combining with chlorpheniramine worsens dry mouth, constipation, blurred vision, and urinary retention
• Serotonergic drugs (e.g., certain antidepressants, triptans) — risk of serotonin syndrome, a potentially life-threatening reaction
• Diuretics — codeine may reduce their effectiveness; monitor blood pressure and urine output

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Children under 18: This medication is not approved for anyone under 18; it is outright contraindicated in children under 12 and in anyone under 18 after tonsil or adenoid surgery
• Pregnancy: Not recommended during pregnancy — prolonged use can cause neonatal opioid withdrawal syndrome (a serious withdrawal condition in the newborn) and potential fetal harm
• Breastfeeding: Do not breastfeed while taking this medication — codeine and its active metabolite morphine pass into breast milk and can cause fatal breathing problems in a nursing infant
• History of addiction or substance use disorder: Codeine carries real addiction risk; inform your prescriber if you or a family member has a history of drug or alcohol dependence
• Lung conditions: People with COPD, severe asthma, or other respiratory diseases are at much higher risk of dangerous breathing suppression
• Older, frail, or debilitated adults: More sensitive to respiratory depression due to changes in how the body processes codeine; requires close monitoring
• Severe kidney or liver impairment: Use with caution — the body may process codeine more slowly, increasing risk of buildup and side effects
• Head injuries or increased intracranial pressure: Avoid use — codeine can raise pressure inside the skull and mask worsening neurological symptoms
• Seizure disorders: Tell your doctor; seizures have been reported and monitoring is needed
• Gastrointestinal obstruction or paralytic ileus: Contraindicated — codeine slows the gut and can worsen a blockage
• Ultra-rapid CYP2D6 metabolizers: If you know you have this genetic trait, do not use this medication — you may convert codeine to dangerously high morphine levels

A codeine overdose can cause breathing to slow dramatically or stop, extreme sleepiness progressing to unconsciousness, pinpoint (very small) pupils, limpness, cold and clammy skin, low blood pressure, and in severe cases, cardiac arrest and death. Chlorpheniramine overdose may add agitation, hallucinations, rapid heart rate, seizures, or coma. If an overdose is suspected, call 911 immediately — the opioid reversal drug naloxone can help counter codeine's effects on breathing, but continued close monitoring is essential because Tuxarin ER continues releasing codeine for hours after ingestion.

Codeine directly depresses the brain's breathing control centers, reducing how often and how deeply a person breathes — which is both its therapeutic effect (suppressing cough) and its most dangerous risk. It also slows movement through the digestive tract, causing constipation, and causes blood vessels to widen, which can lead to a drop in blood pressure when standing. Chronic use of codeine can disrupt hormone systems, potentially causing reduced libido, sexual dysfunction, or irregular periods. Chlorpheniramine blocks histamine from dilating small blood vessels and causing swelling in the airways, relieving allergy-related congestion and runny nose.

After taking Tuxarin ER, codeine reaches peak blood levels in about 3 hours and has a half-life (the time for half the drug to leave your body) of approximately 4 hours. Chlorpheniramine peaks more slowly — around 5 to 6 hours — and stays in the body much longer, with a half-life of about 21 hours. Codeine is broken down primarily in the liver, with a portion converted to morphine (the active pain- and cough-suppressing compound) through an enzyme called CYP2D6; about 90% of codeine and its breakdown products are excreted through the kidneys. Food — even a high-fat meal — does not significantly change how Tuxarin ER is absorbed. Both codeine and chlorpheniramine pass into breast milk and cross the placental barrier.

Store at 20 to 25°C (68 to 77°F) . Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.