Promethazine

Boxed warning:¹

Promethazine has a boxed warning. The drug should not be used in children under two years old because of the risk of respiratory depression. Respiratory depression has occurred with a range of weight-based doses, and fatalities have been reported.

When considering promethazine for children aged two years and older, doctors should prescribe the lowest effective dose and avoid prescribing the drug alongside other drugs with respiratory depressant effects.

The injectable form of this medication has an additional warning highlighting the risk of severe tissue injury. Patients have experienced adverse reactions, including pain, burning, thrombophlebitis (inflammation of a vein), tissue necrosis, and gangrene. Some people have needed surgery after a promethazine injection for procedures such as skin grafts, fasciotomies, and amputations. Thus, the recommended routes of injection are deep intramuscular or intravenous. The drug should not be injected intra-arterial or subcutaneously.² 

What is promethazine?

Promethazine is an antihistamine, antidopaminergic, and anticholinergic drug used to treat various conditions in children and adults. It works by blocking dopamine, histamine, and acetylcholine within the body to produce antiallergy, antiemetic, and sedative effects. ⁴

Promethazine is sold in generic and branded forms (Promethegan, Phenergan) and also in combination products. It is available by prescription only as a tablet and liquid for oral administration, a rectal suppository, and an injectable form. It is approved by the US Food and Drug Administration (FDA) for the following indications:⁵ ⁶

• Allergies (perennial and seasonal allergic rhinitis and conjunctivitis) and vasomotor rhinitis

• Allergic reactions manifesting as hives and angioedema

• Anaphylaxis in combination with epinephrine after the initial symptoms have been controlled

• Motion sickness (given before as prevention and during the event)

• Prevention and treatment of anesthesia-related and post-surgical nausea and vomiting

• Control of postoperative pain combined with other pain medications

• Sedation (used in conjunction with other sedatives and pain medications before and after surgery and for obstetrics)

Promethazine is sometimes used off-label for the treatment of sleep disorders or severe nausea and vomiting associated with pregnancy when other medicines have failed to control the symptoms.⁷

How do you take promethazine?

Your doctor will determine an appropriate form, dosage, and dosing schedule based on:⁸

• Your age (and weight in children)

• Your body’s reaction to an initial dose

• The condition being treated (and its severity)

• Other conditions you have or medications you take that may affect your body’s handling of the drug

Drug forms and strengths⁹

Promethazine tablets (generic) are available in the following strengths:

• 12.5mg

• 25mg

Rectal suppositories (generic, Promethegan) are available in the same three strengths:

• 12.5mg

• 25mg

• 50mg

The injectable solution (generic, Phenergan) is available in two concentrations:

• 25mg/mL

• 50mg/mL

Promethazine syrup/oral solution (generic) comes in a single strength:

• 6.25mg/5mL

Promethazine is contraindicated in children under two years old.¹⁰

How you take promethazine will depend on the form you were prescribed and the condition being treated. Your doctor will decide how much of the drug you need and how often. If you’re unsure, don’t hesitate to ask your doctor or pharmacist for clarification.

Seeing results

When administered intravenously, promethazine begins to work within 3–5 minutes. When administered intramuscularly or in its oral or suppository forms, the drug begins to work within 20 minutes.¹¹

Who should not take promethazine?

Certain people should not take promethazine. The drug is contraindicated for children under two years old and in people who have any of the following:¹²

• Known sensitivity to the drug or any of its components

• Altered level of consciousness or taking large doses of CNS depressants (like pain medications and sedatives)

• Lower respiratory tract symptoms (including asthma and COPD)

Additionally, the drug should be prescribed cautiously for people with any of the following conditions:¹³ ¹⁴ ¹⁵

• Seizure disorders (or those taking medications that lower the seizure threshold)

• Bone marrow depression (and those taking marrow-toxic agents)

• Respiratory depression or impairment

• Sleep apnea

• Liver impairment or changes in the brain linked to chronic liver disease (hepatic encephalopathy)

• Peptic ulcer disease

• Cardiovascular or cerebrovascular disease, heart failure, recent heart attack, heart block, rhythm disturbances (including long QT syndrome)

• Low blood pressure (or risk of, and those taking medications that lower blood pressure or slow the heart rate)

• Slowed digestion or gastrointestinal obstruction

• Urinary retention or obstruction

• Enlarged prostate

• Dry mouth or eyes (including dry eyes caused by contact lenses)

• Myasthenia gravis

• Reye syndrome

• Narrow-angle glaucoma

• Human immunodeficiency virus (HIV)

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Hyperparathyroidism (overactive parathyroid) or hypothyroidism (underactive thyroid)

• Hypocalcemia (low calcium levels in the blood), hypomagnesemia (low magnesium), or hypokalemia (low potassium)

• Sleep deprivation

• Pheochromocytoma (a type of neuroendocrine tumor)

• Diabetes mellitus

• Stroke

And precautions should be taken for people who routinely perform hazardous tasks, those who expect to be exposed to extreme temperatures (or whose body temperature is elevated from strenuous physical activity), people taking anticholinergics (including some antidepressants and antihistamines), and those undergoing chemotherapy or apheresis.

Warnings and potential side effects of promethazine

Promethazine is associated with a broad range of side effects, most of which are mild and self-limiting. Occasionally, promethazine triggers severe adverse effects that require urgent medical attention.¹⁶ ¹⁷

More common side effects

The most common side effects of promethazine include the following:

• Drowsiness

• Itchiness

• Stuffy nose

• Lethargy

• Trouble sleeping

• Vision problems, including blurred or double vision

• Dizziness and coordination difficulties

• Ringing in the ears

• Nausea and vomiting

• Nervousness or restlessness

• Hyperactivity

• Unusually happy mood

• Sore throat or hoarseness

• Urinary retention

• Sun sensitivity

Typically, common and mild side effects resolve without intervention within a few days to weeks. Discuss with your doctor any persistent or worrisome side effects you are experiencing.

Serious side effects

Promethazine may also trigger severe and life-threatening side effects. Reach out to your doctor immediately if you experience any of the following serious adverse effects, as some may require urgent medical attention. If you suspect you’re experiencing a medical emergency, call 911.

Severe side effects of promethazine include the following:

• Fever or chills

• Sweating

• Difficulty breathing, including wheezing, slow breathing, or breathing that stops for a short period

• Difficulty swallowing

• Feeling faint

• Muscle stiffness or spasms

• Unusual or uncontrollable movements or shaking (including body, eyes, or tongue)

• Fast, slow, or irregular heartbeat

• Lack of alertness or responsiveness

• Hallucinations

• Confusion or disorientation

• Extreme fear or emotion

• Seizures

• Unexplained bruising or bleeding

• Abnormal neck position

• Yellowing of the skin or eyes

• Rash or hives

• Swelling of the face, eyes, lips, tongue, throat, limbs, or extremities

People taking promethazine must stay vigilant in monitoring for signs and symptoms of the following severe conditions that may develop while taking the drug:

• Respiratory depression (shortness of breath, slow, shallow breathing, blue lips, fingers, or toes, tiredness, difficulty thinking, and change in level of consciousness)

• CNS depression (confusion, poor concentration, headache, dizziness, lightheadedness, and fainting)

• Neuroleptic malignant syndrome (very high fever, excessive sweating, altered mental status, muscle rigidity, unstable blood pressure, and fast or irregular heartbeat)

• Reduced white blood cell count linked to bone marrow depression (fever and other signs of infection)

• Lowered seizure threshold (seizures)

Overdoses

If you suspect you might have overdosed on promethazine, call the Poison Control Helpline immediately. If someone in your care has taken too much promethazine and has collapsed, had a seizure, fallen unconscious, or is struggling to breathe, call 911.

Other signs of an overdose may include the following:¹⁸

• Slowed breathing or pauses in respirations

• Rapid heart rate

• Dizziness or lightheadedness

• Loss of consciousness or fainting

• Muscle tightness causing difficulty moving

• Continuous twisting movements in the extremities

• Poor coordination

• Dilated or fixed pupils

• Dry mouth

• Nausea or vomiting

• Constipation

• Flushing

• Excitability or agitation

Allergy information

Some people are allergic to promethazine. Signs of a drug allergy include:

• Difficulty breathing or wheezing

• Swelling around the mouth, throat, or tongue

• Skin rash, peeling, or hives

• Vomiting

• Loss of consciousness

If you’ve taken promethazine and are experiencing signs of an allergic reaction, seek emergency medical care. 

Long-term use of promethazine

Doctors typically prescribe promethazine for short-term use. You should stop taking the drug at the end of your prescribed treatment period, as the risk of side effects increases when the drug is taken for long periods.¹⁹

Promethazine and pregnancy

Pregnancy²⁰

The US FDA designated promethazine as a pregnancy category C drug. There are no adequate studies on pregnant women to assure safety, but the drug can be prescribed during pregnancy if a doctor determines the benefits outweigh the potential risk.²¹ ²²

If you're pregnant or planning to conceive, speak with your doctor.

The drug should not be taken in the two weeks leading up to delivery as it may affect platelet function in the newborn.

Breastfeeding²³

If possible, speak with your doctor before you give birth to allow plenty of time to gradually discontinue promethazine, if necessary. It’s not known whether the drug passes through breast milk, and you may need to choose between breastfeeding and continuing treatment. 

Missed doses

After the initial dose, promethazine is often taken as needed up to a certain maximum daily dose. If you forget to take a dose, take it as soon as you remember. If it's nearly time for your next dose, skip the missed dose and resume your usual dosing schedule.

Do not take a double dose of promethazine to make up for a missed one, as this may trigger unwanted side effects.

Drug interactions

Promethazine may interact with other drugs, herbs, supplements, or vitamins you take regularly or occasionally.

The following information on drug interactions is not exhaustive. You can reduce your risk of experiencing severe interactions by providing a complete list of everything you take when you meet with your doctor about starting promethazine. If you are taking promethazine and suspect you’re experiencing a drug interaction, speak with your doctor.

Promethazine is known to interact with the following types of drugs:²⁴ ²⁵ ²⁶

Central nervous system (CNS) depressants

Promethazine depresses CNS activity, so it can amplify the effects of other CNS depressants, including alcohol, narcotics, tricyclic antidepressants, tranquilizers, general anesthetics, sedatives, sleeping pills, muscle relaxants, cannabinoids, and hypnotics. Your doctor may advise you to avoid other CNS depressants entirely. If you need to continue taking them, your doctor may reduce your dose. It is recommended to avoid drinking alcohol while taking promethazine.

Monoamine oxidase inhibitors (MAOIs)

Using promethazine alongside MAOIs, such as isocarboxazid (Marplan), phenelzine (Nardil), and selegiline (Emsam), may increase the risk of experiencing extrapyramidal effects — involuntary drug-induced movements.

Anticholinergics

Promethazine blocks the actions of the neurotransmitter acetylcholine and should be used cautiously alongside other anticholinergics, such as glycopyrrolate (Robinul), scopolamine (Scopace), hyoscyamine (Levsin), and benztropine (Cogentin). 

Promethazine is also contraindicated for people taking the following:

• Potassium chloride

• Potassium citrate

• Potassium phosphate

• Potassium acid phosphate

• Saquinavir (Invirase)

• Yohimbe

And should be avoided by patients using the following medications:

• Alpha-blockers, such as doxazosin (Cardura) and prazosin (Minipress)

• Antibiotics, including amoxicillin and clarithromycin (Biaxin)

• Antipsychotic drugs, including risperidone (Risperdal), olanzapine (Zyprexa), thioridazine (Mellaril), and pimozide (Orap)

• Epilepsy medications, such as valproic acid (Depakote), pregabalin (Lyrica), vigabatrin (Sabril), zonisamide (Zonegran), and phenobarbital

• Selective serotonin reuptake inhibitors (SSRIs) like citalopram (Celexa) and serotonin norepinephrine reuptake inhibitors (SNRIs) like desvenlafaxine (Pristiq)

Notably, promethazine also has known home and laboratory test interactions and may interfere with the results of glucose tolerance and pregnancy tests.

What to discuss with your doctor before you start taking promethazine

Promethazine is available by prescription only, so you’ll need to meet with your doctor before you can start taking it. At your appointment, you should discuss the following topics:

• Any allergies you have to medications or other substances

• Any medical conditions you have, particularly asthma, COPD, liver disease, glaucoma, bone marrow disease, diabetes, heart disease, a recent heart attack, abnormal heart rhythms, an enlarged prostate, or a seizure disorder²⁷

• All vitamins, supplements, and medications you take, whether regularly or occasionally

• Any adverse effects or reactions you’ve had in the past after taking a medication

• Current or planned pregnancies or breastfeeding

• Upcoming surgeries, including dental procedures

• Whether or not it’s safe to drink alcohol

Stopping promethazine

If you've been taking promethazine for a while and then suddenly stop taking it, you may experience some of the following symptoms:

• Dizziness

• Sweating

• Nausea

• Irregular or fast heartbeat

• Trouble sleeping

If you decide to stop taking promethazine, your doctor can help you do so safely.

Drug approval history

1951: The US FDA approved promethazine under the brand name Phenergan.²⁸

2004: The US FDA required the addition of a boxed warning highlighting the contraindication for use in children younger than two years and a strong caution regarding use in children two and older.²⁹

2005: The US FDA approved generic versions of promethazine tablets.³⁰

2009: The US FDA required the addition of a boxed warning detailing the risks of severe tissue injury (including gangrene) associated with the injectable formulation of promethazine.³¹

Tips and advice for taking promethazine

The following tips can help you take promethazine safely:

• If you’ve been prescribed an oral form of promethazine, taking it with food may lessen stomach upset.

• Measure the liquid formulation using a pharmaceutical dosing syringe that should be provided for you. Don’t rely on home utensils, as they may not be accurate for medication dosing.

• If you’re using suppositories, run the tip of the suppository under water to make it easier to insert.

• Avoid alcohol or over-the-counter sedative medications while taking promethazine.

• Don't engage in activities requiring absolute focus or quick reactions until you know how your body handles promethazine.

• Do not rely on the results of home pregnancy tests while taking promethazine, as the drug may trigger a false positive or false negative.³²

• Promethazine may increase your skin’s sensitivity to sunlight. Wear protective clothing, sunglasses, and sunscreen, and avoid prolonged exposure.³³

Promethazine FAQs

Is promethazine a narcotic?

No, promethazine is not a narcotic. However, some medications combine promethazine with codeine to treat cold symptoms, and codeine is a narcotic.³⁴ ³⁵

Does promethazine make you feel strange?

Promethazine has a wide range of side effects, including drowsiness, nervousness, and unusual happiness. Most of its side effects are mild and nothing to worry about, but some, such as extreme emotions, confusion, and hallucinations, are serious and demand urgent medical attention. If you notice anything unusual while taking promethazine, consult your healthcare professional. See Warnings and potential side effects of promethazine for more information on how promethazine can make you feel.