What to Know About Promethazine

First-generation antihistamine has its benefits and risks

In This Article

Promethazine is a first-generation antihistamine used to treat allergies, nausea, and motion sickness. In a hospital setting, promethazine is often used to treat anaphylaxis and provide mild sedation before or after surgery. The drug can be taken by mouth as a tablet or syrup, injected into a muscle, or delivered as a rectal suppository. Common side effects include drowsiness, blurred vision, and dry mouth.

Promethazine is available by prescription only, although it can be found as an ingredient in certain over-the-counter cough syrups and motion sickness remedies. Promethazine is sold as a generic and under a wide variety of brand names, including Phenadoz, Phenergan, and Promethegan.

Promethazine should never be used in children under 2 years old. Doing so may cause abnormally slowed breathing and, in some cases, death.

Uses

Promethazine is classified as an H1 receptor antagonist, meaning that it blocks the action of histamine. Histamine is an inflammatory compound involve in many immune processes. When released in excess, histamine can cause swelling, itching, sneezing, and other symptoms of allergy. By binding to H1 receptors on tissues, promethazine prevents the attachment of histamine and, with it, the development of symptoms.

Promethazine blocks other compounds, most notably the neurotransmitter acetylcholine. By doing so, promethazine can slow motility in the gastrointestinal tract. It can also penetrate the blood-brain barrier and act directly on the central nervous system, reducing nausea and delivering mild sedative effects.

The indications of use for promethazine include:

  • Seasonal allergy ("hay fever")
  • Allergic conjunctivitis ("pink eye")
  • Mild sedation in adults and children
  • Pre-operative sedation
  • Post-operative nausea and vomiting (associated with anesthesia or surgery)
  • Post-operative pain (used in adjunct with an analgesic like Demerol)
  • Motion sickness (when co-formulated with ephedrine or pseudoephedrine)
  • Cough (when co-formulated with codeine or dextromethorphan)
  • Anaphylaxis (used in adjunct with epinephrine and other medications to counteract the potentially life-threatening hyperallergic reaction)

Promethazine belongs to a family of drugs called phenothiazines which also includes Thorazine (chlorpromazine) and Stelazine (trifluoperazine). But, unlike those drugs, promethazine is not used as an antipsychotic.

Off-Label Uses

Promethazine is sometimes used off-label to treat morning sickness and hyperemesis gravidarum (a pregnancy complication characterized by severe nausea, vomiting, weight loss, and dehydration). According to the American College of Obstetrics, promethazine may be used for these purposes during pregnancy when conservative treatments fail to provide relief.

Promethazine is sometimes used to treat severe agitation and restlessness in people with psychiatric conditions, although there are no guidelines directing the appropriate use of the drug in such circumstances.

Promethazine is also sometimes used off-label to treat migraines. However, this practice has largely fallen out of favor given the introduction of newer drugs that are not only more effective but have fewer side effects.

Before Taking

The appropriate use of promethazine can vary based on its intended use.

When used for the treatment of seasonal allergy or allergic conjunctivitis, second-generation antihistamines like Allegra (fexofenadine) and Claritin (loratadine) are preferred over promethazine as they are available over-the-counter and cause less drowsiness. Promethazine should be considered if these second-generation antihistamines fail to provide relief.

The same would apply to the use of promethazine in treating morning sickness or motion sickness. Because of its sedating effect, promethazine should only be used if other conservative therapies are unable to relieve nausea symptoms.

The use of promethazine in a hospital setting is directed by a physician.

Precautions and Contraindications

There are situations in which promethazine is contraindicated for use. This would include the avoidance of the drug in people with a known sensitivity to promethazine or other phenothiazines.

In 2004, the U.S. Food and Drug Administration issued two separate black box warnings advising consumers and health professionals about potentially life-threatening risks of promethazine use.

Black Box Warnings

Promethazine in any form (oral, injection, suppository) should never be used in children under two due to the risk of slowed breathing (respiratory depression). Fatalities have been reported.

Promethazine should never be injected subcutaneously (into the skin) as this can cause tissue death and gangrene. Such injections have led to limb amputations and skin grafts.

Even intravenous injections (into a vein) can irritate and/or damage vascular tissues. Although intravenous injections are not contraindicated, the FDA advises that intramuscular injections (into deep muscle) remain the preferred route.

Similarly, the FDA issued a black box warning advising against the use of cough syrups containing promethazine and codeine in younger children. This co-formulated syrup is also associated with an increased risk of respiratory depression and is contraindicated for use in children under six.

Dosage

Promethazine is available in several formulations. Oral tablets and syrups work relatively fast and deliver symptom relief within 20 minutes. Rectal suppositories are typically prescribed when oral formulations cannot be used.

Promethazine injections usually work within five minutes and last four times longer than either tablets, syrups, or suppositories.

Promethazine is offered in the following formulations:

  • Tablet: 12.5 milligrams (mg), 25 mg, and 50 mg
  • Syrup: 6.25 milligrams per 5 milliliters (6.25 mg/5 mL)
  • Suppository: 12.5 mg, 25 mg, and 50 mg
  • Injectable solution: 25 mg per deciliter (mg/dL), 50 mg/dL

The dosing recommendations vary by the age of the user and the condition being treated.

Dosing Guidelines
  Adults Children 2 and older
Allergy Oral/rectal: 25 mg at bedtime or two 12.5 mg doses taken once at mealtime and once at bedtime
Injection: 25 mg, repeated in two hours if needed
Oral/rectal: same as adults
Injection: same as adults
General sedation Oral/rectal 25 to 50 mg taken before bedtime Oral/rectal: 12.5 to 25 mg taken before bedtime
Nausea and vomiting Oral/rectal: 12.5 to 25 mg taken every 4 to 6 hours
Injection: 12.5 mg to 25 mg taken every 4 to 6 hours
Oral/rectal: 0.25 to 1.0 mg per kilogram (mg/kg) taken every 4 to 6 hours 
Motion sickness Oral/rectal: 25 mg taken 30 to 60 minutes before departure and every 8 to 12 hours thereafter if needed Oral/rectal: 12.5 to 25 mg taken 30 to 60 minutes before departure and every 8 to 12 hours thereafter if needed
Pre-operative sedation Oral/rectal: 50 mg taken the night before the procedure
Injection: 25 to 50 mg delivered before the procedure
Oral/rectal: 1 mg/kg taken the night before the procedure
Post-operative sedation Oral/rectal: 25 to 50 mg
Injection: 25 to 50 mg
Oral/rectal: 12.5 to 25 mg
Labor Injection: 25 to 50 mg during early labor, increasing to 25 to 75 mg once labor is established  Not applicable

Modifications

When used to treat seasonal allergies, promethazine should be reduced to the lowest possible dose once the acute symptoms have been relieved. Prolonged or frequent use can cause skin darkening (hyperpigmentation) and increase the risk of drug allergy (even more than a large single dose).

How to Take and Store

It is important to take promethazine as prescribed to achieve the intended effect. If you are unsure of how to take promethazine, ask your doctor or pharmacist. Among the general guidelines for use:

  • Promethazine tablets are typically round and white; some are scored and others are not. The pills can be taken with or without food
  • Promethazine syrup is made with artificial berry flavoring. Each dose should be carefully measured with a 5-milliliter (mL) spoon. Avoid using a tablespoon or kitchen spoon as this could lead to overdosing.
  • Promethazine suppositories are torpedo-shaped and made with a combination of white wax and cocoa butter that melts at body temperature. Gently insert the suppository into the anus, narrow end first, pushing it up 1 inch in adults and a 0.5 to 1 inch in children.
  • Promethazine injection solution is packaged in single-use, 1-mL vials. The injection is typically delivered into a deep muscle (such as the buttocks) by a health professional. If used intravenously, it is typically used with other intravenous drugs or fluids.

Promethazine tablets, syrup, and injection solution should be stored at room temperature between 68 F and 77 F (20 C and 25 C). Keep away from direct sunlight in their original light-resistant containers.

Unlike tablets or syrup, promethazine suppositories need to be refrigerated at temperatures of between 36 F and 46 F (2 C and 8 C).

Never use promethazine past its expiration date.

Side Effects

As with any drug, promethazine may cause side effects, particularly in the early stages of treatment. Milder ones tend to resolve on their own as the body adapts to the medication. Serious ones may require the termination of treatment.

Common

The side effects of promethazine are extensive and may include:

  • Drowsiness
  • Disorientation
  • Blurred or double vision
  • Dizziness
  • Fatigue
  • Nausea or vomiting
  • Nasal stuffiness
  • Xerostomia (dry mouth)
  • Tinnitus (ringing in the ears)
  • Photosensitivity (increased sensitivity to sunlight)
  • Nervousness and excitability
  • Euphoria
  • Insomnia
  • Tremors
  • Heart palpitations

Severe

Promethazine can sometimes cause side effects that require immediate medical attention. These include:

  • Bradypnea (slow breathing)
  • Bradycardia (slowed heartbeat)
  • Tachycardia (rapid heartbeat)
  • Angioedema (swelling of the tissues beneath the skin)
  • Cyanosis (blueish skin, lips, toes, or fingers)
  • Jaundice (yellowing of the skin or eyes)
  • Hives or rash
  • Hallucinations
  • Delirium
  • Seizures
  • Muscle rigidity
  • Tardive dyskinesia (involuntary movements, such as the sudden upward turning of the eyes, twisting of the head to one side, or jutting of the tongue)

Symptoms like these may be signs of a drug reaction, liver toxicity, respiratory depression, or a condition known as neuroleptic malignant syndrome (NMS). None of these signs should ever be ignored. Even non-fatal symptoms like tardive dyskinesia may become permanent if treatment is continued.

When to Call 911

Call 911 if there are signs of respiratory depression (slowed breathing, shortness of breath, and blueish skin), NMS (fever and muscle rigidity), or anaphylaxis (hives, wheezing, rapid heart rate, and swollen face or tongue). If not treated immediately, these conditions can be fatal.

Warnings and Interactions

There are a number of circumstances in which promethazine should be avoided or used with caution. Although not specifically contraindicated for use, promethazine may pose in certain people. Among the concerns:

  • Driver impairment: Promethazine should not be used if you intend to drive or use heavy machinery. The sedative effect may be amplified if the drug is taken with alcohol or any other nervous system depressant.
  • Chemotherapy: Promethazine should be used with caution in people on chemotherapy or any medication the causes bone marrow suppression. Doing so can lead to a potentially severe drop in the white blood cell (WBC) count.
  • Liver disease: Promethazine should be used with caution in people with liver impairment. Because promethazine is metabolized by the liver, any impairment can lead to liver toxicity.
  • Pregnancy: Promethazine is a Pregnancy Category C drug, meaning that animal studies have shown a potential risk for birth defects but well-controlled studies in humans are not yet available. As such, the benefits and risks of treatment should be weighed before promethazine is used.

Promethazine may interfere with the accuracy of pregnancy tests by increasing or decreasing levels of human chorionic gonadotropin (hCG). Doing so can lead to false-negative or false-positive results.

Interactions

Promethazine can interact with certain drugs, often by amplifying their action along with their adverse effects. These include anticholinergic drugs that block the action of acetylcholine and monoamine oxidase inhibitors (MAOIs) used to treat mood and anxiety disorders.

Advise your doctor if you have been prescribed promethazine and take any of the following drugs:

  • Atropen (atropine)
  • Atrovent (ipratropium)
  • Azilect (rasagiline)
  • Cogentin (benztropine mesylate)
  • Cyclogyl (cyclopentolate)
  • Detrol (tolterodine)
  • Ditropan XL (oxybutynin)
  • Emsam (selegiline)
  • Enablex (darifenacin)
  • Hyoscine (scopolamine)
  • Levsinex (hyoscyamine)
  • Marplan (isocarboxazid)
  • Nardil (phenelzine)
  • Parnate (tranylcypromine)
  • Spiriva (tiotropium)
  • Toviaz (fesoterodine)
  • Urispas (flavoxate)
  • VESIcare (solifenacin)

In some cases, a dose adjustment or drug substitution may be needed. To avoid interactions, always advise your doctor about any drugs you are taking, whether they are prescription, over-the-counter, nutritional, herbal, or recreational.

Never stop taking any chronic medication, especially MAOIs, without first speaking with your doctor. Doing so may cause withdrawal symptoms and other adverse events.

Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. U.S. National Library of Medicine. Compound summary: Promethazine. Updated February 15, 2020.

  2. Monczor F, Fernandez N. Current knowledge and perspectives on histamine H1 and H2 receptor pharmacology: Functional selectivity, receptor crosstalk, and repositioning of classic histaminergic ligands. Mol Pharmacol. 2016;90(5):640-8. doi:10.1124/mol.116.105981

  3. U.S. Food and Drug Administration. Promethazine hydrochloride injection, USP. Revised October 2009.

  4. Wilson MP, Pepper D, Currier GW, Holloman GH Jr, Feifel D. The psychopharmacology of agitation: consensus statement of the American Association for Emergency Psychiatry Project Beta Psychopharmacology WorkgroupWest J Emerg Med. 2012;13(1):26-34. doi:10.5811/westjem.2011.9.6866

  5. Gelfand AA, Goadsby PJ. A neurologist's guide to acute migraine therapy in the emergency room. Neurohospitalist. 2012;2(2):51-9. doi:10.1177/1941874412439583

  6. Recto MT, Gabriel MT, Kulthanan K, et al. Selecting optimal second-generation antihistamines for allergic rhinitis and urticaria in AsiaClin Mol Allergy. 2017;15:19. doi:10.1186/s12948-017-0074-3

  7. U.S. Food and Drug Administration. Phenergan (promethazine HCI) tablets and suppositories. Revised 2004.

  8. U.S. Food and Drug Administration. Promethazine HCl and codeine phosphate oral solution. Revised January 2017.

  9. U.S. Food and Drug Administration. Promethazine HCL plain oral solution. Revised May 2008.

  10. Cantisani C, Ricci S, Grieco T, et al. Topical promethazine side effects: our experience and review of the literatureBiomed Res Int. 2013;2013:151509. doi:10.1155/2013/151509

  11. Kar S, Krishnan A, Preetha K, Mohankar A. A review of antihistamines used during pregnancyJ Pharmacol Pharmacother. 2012;3(2):105-8. doi:10.4103/0976-500X.95503

  12. Bustos M, Venkataramanan R, Caritis S. Nausea and vomiting of pregnancy - What's new?Auton Neurosci. 2017;202:62-72. doi:10.1016/j.autneu.2016.05.002

Additional Reading