promethazine and codeine

What is promethazine and codeine, and how does it work (mechanism of action)?

Promethazine is in a class of drugs called phenothiazines which also includes chlorpromazine, and trifluoperazine; however, unlike the other drugs in this class, promethazine is not used as an anti-psychotic but rather as an anti-histamine, sedative, antiemetic (anti-nausea), and cough suppressant.

Cells in the body release histamine during several types of allergic reactions. When histamine binds to its receptors on other cells, it stimulates changes within the cells that lead to release of other chemicals that cause sneezing, itching, and increased mucus production. Antihistamines such as promethazine compete with histamine for one of the receptors for histamine (the H1 receptor) on cells; however, when antihistamines bind to the receptors they do not stimulate the cells. Instead, they prevent histamine from binding and stimulating the cells. Promethazine also blocks the action of acetylcholine, a neurotransmitter that nerves use to communicate with one another, 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 and hydrocodone. In fact, a small amount of codeine is converted to morphine in the body. 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, but the pain still is apparent to the patient. In addition to reducing pain, codeine also causes sedation (drowsiness) and depresses breathing. The FDA approved promethazine and codeine in January 1952.

What brand names are available for promethazine and codeine?

(Phenergan with Codeine: This brand no longer is available in the U.S.)

Is promethazine and codeine available as a generic drug?


Do I need a prescription for promethazine and codeine?


What are the side effects of promethazine and codeine?

WARNING 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.

What is the dosage for promethazine and codeine?

The usual adult dose is one teaspoonful every 4 to 6 hours as needed. The maximum dose is two tablespoons daily.

Which drugs or supplements interact with promethazine and codeine?

Excessive sedation may occur when promethazine and codeine is combined with other medications that cause sedation. Such drugs include ethanol, barbiturates, anti-anxiety medications, sedatives, other phenothiazines, and narcotic pain medications.

Promethazine should not be taken with any of the monoamine oxidase (MAO) inhibitor class of antidepressants, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane), because of the increased risk of extrapyramidal symptoms (EPS) - uncontrollable movement disorders. Excessive anti-cholinergic effects (described below) can occur when promethazine is used with other antihistamines, for example, diphenhydramine (Benadryl), some phenothiazines, for example, thioridazine,  some tricyclic antidepressants, for example, amitriptyline, clozapine (Clozaril, FazaClo, Versacloz), cyclobenzaprine (Active-Cyclobenzaprine, Amrix, EnovaRX-Cyclobenzaprine HCl, Fexmid)), and disopyramide (Norpace).

There may be an increase in the risk of certain neurologic reactions that affect movement of muscles (EPS, see below) when promethazine is combined with medicines that also cause EPS. Such drugs include antipsychotics, metoclopramide (Metozolv ODT, Reglan), and amoxapine.

Promethazine should not be used with propylthiouracil (PTU) due to the increased risk of low white blood cell counts and increased risk of infections. The reason for this interaction is not known.

Concurrent use of promethazine with the dye used for myelography (X-rays of the spinal cord) can lower the threshold for seizures and thus increase the risk of seizures. Promethazine should be stopped at least 48 hours before myelography and not restarted until at least 24 hours after myelography.


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Is promethazine and codeine safe to take if I'm pregnant or breastfeeding?

There are no adequate studies of promethazine and 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 not known 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.

What else should I know about promethazine and codeine?

What preparations of promethazine and codeine are available?

Syrup: 6.25mg of promethazine and 10mg of codeine per teaspoonful.

How should I keep promethazine and codeine stored?

Promethazine and codeine should be stored at room temperature, 15C - 25C (59F - 77F) in a tightly closed container protected from light.


Promethazine and codeine (Phenergan with Codeine) is a drug prescribed for the treatment of common cold symptoms and cough. Side effects, drug interactions, warnings and precautions, and efficacy during pregnancy information should be reviewed prior to taking this medication.

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