Does Phenergan with Codeine (promethazine and codeine) cause side effects?

Phenergan with Codeine (promethazine and codeine) is a combination of an anti-histamine, sedative, antiemetic (anti-nausea), and cough suppressant and a weak narcotic pain-reliever and cough suppressant used to treat common cold symptoms and cough.

Promethazine blocks the action of the neurotransmitter acetylcholine on its receptors (anticholinergic effect), and this may explain its benefit in reducing the nausea of motion sickness. It is used as a sedative because it causes drowsiness as a side effect. The cough suppressant effects may be due to is anticholinergic effects.

Codeine is a weak narcotic pain-reliever and cough suppressant similar to morphine. The precise mechanism of action of codeine is not known; however, like morphine, codeine binds to narcotic receptors in the brain (opioid receptors) that are important for transmitting the sensation of pain throughout the body and brain.

Codeine increases tolerance to pain and decreases discomfort. In addition to reducing pain, codeine also causes sedation (drowsiness) and depresses breathing. The brand name Phenergan with Codeine is no longer is available in the U.S. 

Common side effects of Phenergan with Codeine include

  • dizziness,
  • restlessness,
  • inability to sleep,
  • palpitations, and
  • extrapyramidal symptoms (changes in muscle tone, sharp, involuntary muscle movements often limited to one muscle or muscle group, restlessness, and Parkinsonism).

Withdrawal symptoms may occur if you suddenly stop taking this drug. 

Serious side effects of Phenergan with Codeine include

Drug interactions of Phenergan with Codeine include other medications that cause sedation (because excessive sedation may occur), such as

Promethazine should not be taken with monoamine oxidase inhibitors (MAOIs) because of the increased risk of extrapyramidal symptoms (EPS).

Excessive anti-cholinergic effects can occur when promethazine is used with

There may be an increase in the risk of certain neurologic reactions that affect movement of muscles when promethazine is combined with medicines that also cause EPS such as

Promethazine should not be used with propylthiouracil (PTU) due to the increased risk of low white blood cell counts and increased risk of infections. Concurrent use of promethazine with dye used for myelography (X-rays of the spinal cord) can lower the threshold for seizures and thus increase the risk of seizures.

There are no adequate studies of Phenergan with Codeine in pregnant women. Administration of promethazine within two weeks of delivery may affect platelet function in the newborn.

Codeine generally is avoided during pregnancy because it may cause

  • fetal physical dependence,
  • withdrawal and
  • growth retardation.

It is unknown if promethazine is excreted in breast milk. Small amounts of codeine are secreted in breast milk, but the risk of adverse events in the infant is small. Consult your doctor before breastfeeding.

What are the important side effects of Phenergan with Codeine (promethazine and codeine)?


  • In children less than 6 years of age, promethazine and codeine can depress respiration and lead to death.
  • Therefore, it should not be used in children less than 6 years old.
  • Death has also been reported in children less than 2 years old due to respiratory depression.
  • Although promethazine causes dizziness, it may stimulate activity in patients, particularly children.
  • Such stimulation may be manifest by restlessness, inability to sleep, palpitations (rapid heartbeat) or even seizures.

Extrapyramidal symptoms (EPS) may occur. EPS are categorized as

  • dystonic reactions (alterations in muscle tone),
  • sharp, involuntary muscle movements often limited to one muscle or muscle group,
  • akathisia (subjective restlessness), and
  • Parkinsonism.

Parkinsonian symptoms are more common in older persons whereas children more often develop involuntary muscle movement reactions. Dystonic reactions are most commonly seen during the first week of treatment. Restlessness and Parkinsonian symptoms usually develop days to weeks after starting therapy.

A complex called neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines. NMS consists of

  • high body temperature,
  • severe EPS,
  • changes in consciousness and mental status, and
  • increased heart rate with low or high blood pressure.

NMS occurs more frequently in young men and in persons who are dehydrated.

Phenergan with Codeine (promethazine and codeine) side effects list for healthcare professionals


Central Nervous System

CNS depression, particularly respiratory depression, and to a lesser extent circulatory depression; light-headedness, dizziness, sedation, euphoria, dysphoria, headache, transient hallucination, disorientation, visual disturbances, and convulsions.


Tachycardia, bradycardia, palpitation, faintness, syncope, orthostatic hypotension (common to narcotic analgesics).


Nausea, vomiting, constipation, and biliary tract spasm. Patients with chronic ulcerative colitis may experience increased colonic motility; in patients with acute ulcerative colitis, toxic dilation has been reported.


Oliguria, urinary retention, antidiuretic effect has been reported (common to narcotic analgesics).


Infrequent pruritus, giant urticaria, angioneurotic edema, and laryngeal edema.


Flushing of the face, sweating and pruritus (due to opiate-induced histamine release); weakness.


Central Nervous System

Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness, confusion, disorientation and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported.


Increased or decreased blood pressure, tachycardia, bradycardia, faintness.


Dermatitis, photosensitivity, urticaria.


Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.


Dry mouth, nausea, vomiting, jaundice.


Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal).


Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported.

Paradoxical Reactions

Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine HCl. Consideration should be given to the discontinuation of promethazine HCl and to the use of other drugs if these reactions occur.

Respiratory depression, nightmares, delirium and agitated behavior have also been reported in some of these patients.

Does Phenergan with Codeine (promethazine and codeine) cause addiction or withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance

Promethazine HCl and Codeine Phosphate Oral Solution is a Schedule V Controlled Substance.


Codeine is known to be subject to abuse; however, the abuse potential of oral codeine appears to be quite low. Even parenteral codeine does not appear to offer the psychic effects sought by addicts to the same degree as heroin or morphine. However, codeine must be administered only under close supervision to patients with a history of drug abuse or dependence.


Psychological dependence, physical dependence, and tolerance are known to occur with codeine.

What drugs interact with Phenergan with Codeine (promethazine and codeine)?

Codeine: In patients receiving MAO inhibitors, an initial small test dose is advisable to allow observation of any excessive narcotic effects or MAOI interaction.


CNS Depressants

Promethazine may increase, prolong or intensify the sedative action of other central-nervous-system depressants, such as

Therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine HCl. When given concomitantly with promethazine, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half.

Dosage must be individualized. Excessive amounts of promethazine HCl relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.


Because of the potential for promethazine to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine overdose.


Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

Monoamine Oxidase Inhibitors (MAOI)

Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly.

Drug/Laboratory Test Interactions

Because narcotic analgesics may increase biliary tract pressure, with resultant increase in plasma amylase or lipase levels, determination of these enzyme levels may be unreliable for 24 hours after a narcotic analgesic has been given.

The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride:

Pregnancy Tests

Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.

Glucose Tolerance Test

An increase in blood glucose has been reported in patients receiving promethazine.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 7/2/2020
FDA Prescribing Information

Professional side effects, drug interactions, and addiction sections courtesy of the U.S. Food and Drug Administration.