What to Know About Promethazine

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.

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 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.

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.

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.

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.

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.

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).

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.

Never use promethazine past its expiration date.

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.

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

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.

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 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.