Codeine/Chlorpheniramine

DEA Class; Rx

Common Brand Names; Tuzistra XR, Tuxarin ER

Oral sedating antihistamine and opiate agonist antitussive combination
Used in adults for temporary relief from cough and other symptoms due to hay fever, upper respiratory allergies, or allergic rhinitis
Safety and efficacy not established in pediatric patients under 18 years of age; contraindicated for cough and cold in all pediatric patients less than 12 years of age and in adolescent pediatric patients 12 to 18 years after tonsillectomy or adenoidectomy

Indicated for relief of cough and symptoms associated with upper respiratory tract allergies or common cold in adults (>18 years)

Known hypersensitivity to codeine, chlorpheniramine, or product components

Children <12 years

Post-operative management in children <18 years following tonsillectomy and/or adenoidectomy

Patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within last 14 days

Known or suspected gastrointestinal obstruction, including paralytic ileus

Persons known to be hypersensitive to other opioids exhibiting cross-sensitivity to codeine

Allergic: Allergic laryngospasm, nasal stuffiness, bronchospastic allergic reaction, hives, itching, swelling of face

Body as a whole: Asthenia, feeling of relaxation, redness or flushing of the face, unusual tiredness, weakness

Cardiovascular: Fast or slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitations, shock-like state, syncope

Dermatological system: Skin rash, pruritus, erythema, urticaria, excessive perspiration, dermatitis

Endocrine system: Changes in glucose utilization, decreased lactation, early menses, glycosuria, gynecomastia, hypoglycemia, increased appetite, increased libido, pheochromocytoma stimulation

Gastrointestinal system: Nausea and vomiting, constipation, abdominal distension, abdominal pain, acute pancreatitis, dry mouth, dyspepsia, epigastric distress, loss of appetite, diarrhea, gastro-esophageal reflux, gastrointestinal hypomotility

Genitourinary system: Ureteral spasm, urinary retention, dysuria, urinary frequency, urinary hesitancy, irritative bladder symptom

Nervous system: Blurred vision, diplopia, visual disturbances, confusion, dizziness, depression, drowsiness, sedation, headache, euphoria, facial dyskinesia, false sense of well-being, feeling faint, lightheadedness, general feeling of discomfort or illness, excitability, nervousness, agitation, restlessness, somnolence, insomnia, dyskinesia, irritability, tremor

Respiratory: Dryness of the pharynx and respiratory passages, laryngismus, atelectasis, wheezing, troubled breathing, respiratory depression, hiccups

Special senses: Labyrinthitis, tinnitus, vertigo, hypermetropia, increased lacrimation, mydriasis, photophobia

Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (ie, multiple copies of the gene for CYP2D6 or high morphine concentrations) (see Black Box Warnings and Contraindications)

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

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 of time and inform patients and caregivers about risks and the signs of morphine overdose

Produces dose-related respiratory depression (fatalities reported) by directly acting on brain stem respiratory centers; may produce irregular and periodic breathing

At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because mother was an ultra-rapid metabolizer of codeine; breastfeeding not recommended during treatment

Potential for dependence and abuse

Avoid use with head injuries; opioids produce adverse reactions that may obscure the clinical course of patients with head injuries

Codeine and chlorpheniramine produce drowsiness and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks (driving, operating machinery)

Codeine

• As with all opioids, administration of codeine to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used

Chlorpheniramine

• A retrospective study found a small, but statistically significant, association between maternal use of chlorpheniramine and inguinal hernia and eye or ear anomalies in children

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