Promethazine Codeine

Promethazine/Codeine is a prescription medication used to treat cough and upper respiratory tract symptoms associated with allergies or common cold. 

• Promethazine/Codeine is available under the following different brand names: Phenergan-Codeine, Codeine Phosphate-Promethazine HCL, Phenergan with Codeine, Promethazine HCL with Codeine Phosphate, Promethazine with Codeine

Adult and pediatric dosage

Oral liquid: Schedule V

• (6.25mg/10mg)/5mL

Cough

Adult dosage

• 6.25 mg/10 mg (5 mL) orally every 4-6 hours; not to exceed 30 mL/24 hours

Pediatric dosage

• Children younger than 12 years of age: Safety and efficacy not established
• Children 12 years of age: 2.5-5 mL orally every 4-6 hours; not to exceed 30 mL/24 hours
• Children older than 12 years of age: 6.25 mg/10 mg (5 mL) orally every 4-6 hours; not to exceed 30 mL/24 hours

Dosage Considerations – Should be Given as Follows: 

• See "Dosages."

Common side effects of Promethazine/Codeine include:

• dry mouth, 
• nausea, 
• vomiting, 
• constipation, 
• confusion, 
• dizziness, 
• headache, 
• drowsiness, 
• lack of energy, 
• tremors, 
• coordination problems, 
• anxiety, 
• restlessness, 
• nervousness, 
• irritability, 
• urination problems, 
• sweating, and 
• shortness of breath  

Serious side effects of Promethazine/Codeine include:

• hives, 
• difficulty breathing, 
• swelling in the face, lips, tongue, or throat, 
• slow breathing with long pauses, 
• blue colored lips, 
• difficult to wake up, 
• noisy breathing, 
• sighing, 
• shallow breathing, 
• extreme drowsiness, 
• confusion, 
• weakness or limp feeling, 
• uncontrolled muscle movements in the face, neck, arms, or legs, 
• lightheadedness, 
• seizure, 
• nausea, 
• vomiting, 
• loss of appetite, 
• dizziness, 
• worsening tiredness or weakness, 
• very stiff (rigid) muscles, 
• high fever, 
• sweating, 
• confusion, 
• fast or uneven heartbeats, 
• tremors, 
• agitation, 
• hallucinations, 
• shivering, 
• fast heart rate, 
• muscle stiffness, 
• twitching, 
• loss of coordination, and
• diarrhea

Rare side effects of Promethazine/Codeine include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result 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.

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, health care provider or pharmacist first.

• Promethazine/Codeine has severe interactions with the following drugs:
  • alvimopan
  • disopyramide
• Promethazine/Codeine has serious interactions with at least 87 other drugs.
• Promethazine/Codeine has moderate interactions with at least 364 other drugs.
• Promethazine/Codeine has minor interactions with at least 76 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 drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Postoperative use in children following tonsillectomy and/or adenoidectomy (see Black Box Warnings)
• Promethazine
  • Hypersensitivity
  • Children younger than 12 years (risk of potentially fatal respiratory depression)
  • Subcutaneous or intra-arterially administration
  • Benign prostatic hypertrophy
  • Narrow angle glaucoma
  • Pyloroduodenal obstruction, stenosing peptic ulcer, bladder neck obstruction
  • Severe CNS depression
  • Coma, severe respiratory depression
• Codeine
  • Absolute: acute abdominal condition, diarrhea associated w/ toxins, pseudomembranous colitis, respiratory depression
  • Relative: asthma (acute), inflammatory bowel disease, respiratory impairment
  • Children younger than 12 years
  • Postoperative management in children younger than 18 years following tonsillectomy and/or adenoidectomy
  • 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 the last 14 days
  • Significant respiratory depression
  • Porphyria
  • Treatment of lower respiratory tract symptoms, including asthma
  • Known or suspected gastrointestinal obstruction, including paralytic ileus

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Promethazine/Codeine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Promethazine/Codeine?”

Cautions

Concomitant use of opioids, including promethazine HCl and codeine phosphate oral solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol

• Promethazine
  • Caution in CVD, asthma, hepatic impairment, peptic ulcer, respiratory impairment; the impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; avoid use of promethazine HCl and codeine phosphate oral solution in patients on these medications
  • Anaphylaxis in susceptible individuals
  • May impair ability to drive or perform hazardous tasks
  • Monitor closely with cardiovascular disease, hepatic impairment, Reye syndrome, history of sleep apnea
  • Depresses hypothalamic thermoregulatory mechanism; exposure to extreme temperatures may cause hypo- or hyperthermia
  • Antiemetic effect may obscure toxicity of chemotherapeutic drugs
  • Concomitant use of opioids, including promethazine HCl and codeine phosphate oral solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
  • Convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients; promethazine may lower seizure threshold; it should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold
  • Promethazine is a phenothiazine; phenothiazines are associated with dystonic reactions; in pediatric patients who are acutely ill associated with dehydration, there is increased susceptibility to dystonias with promethazine HCl use
  • The respiratory-depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in presence of head injury, intracranial lesions, or a pre-existing increase in intracranial pressure; narcotics may produce adverse reactions which may obscure clinical course of patients with head injuries
  • A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) reported in association with promethazine HCl alone or in combination with antipsychotic drugs; 1) management of NMS should include immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available
  • Promethazine should be used with caution in patients with bone-marrow depression; leukopenia and agranulocytosis reported, usually when promethazine HCl has been used in association with other known marrow-toxic agents
• Codeine
  • Caution in cardiac arrhythmias, drug abuse/dependence, emotional lability, gallbladder disease, head injury, hepatic impairment, hypothyroidism, increased ICP, prostatic hypertrophy, renal impairment, seizures w/ epilepsy, urethral stricture, urinary tract surgery
  • Risk of life-threatening side effects in nursing babies, especially if mother is an ultra-rapid metabolizer of codeine
  • Codeine is subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to an increased exposure to the active metabolite morphine
  • Avoid use of capsules 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
  • Dosage of codeine should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease
  • Narcotic analgesics or cough suppressants, including codeine, should not be used in patients with severe asthma or those with frequent asthma attacks
  • Codeine may produce orthostatic hypotension in ambulatory patients
  • Codeine may cause or aggravate constipation
  • Ibuprofen is more effective than codeine for pain from musculoskeletal injuries in children

Pregnancy and Lactation

• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in 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 prior to 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 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; 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
  • There is no information on effects of codeine milk production; because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment