What is Promethazine? Understanding a First-Generation Antihistamine

October 5, 2025 •

3 min read

First approved in 1951, promethazine (commonly known by the brand name Phenergan) is a versatile, prescription-only medication known for its potent antihistaminic, sedative, and antiemetic properties. It belongs to the phenothiazine class of drugs and is used for a variety of conditions, from allergies to nausea and motion sickness.

Quick Summary

Promethazine is a prescription medication used for allergies, motion sickness, and nausea/vomiting. As a first-generation antihistamine, it works by blocking histamine and other chemicals in the brain, causing sedative effects. It is available in various forms and requires careful dosing due to potential side effects like drowsiness.

Key Points

Drug Class: Promethazine is a first-generation antihistamine and a phenothiazine derivative.
Dual Mechanism: It blocks histamine receptors for allergy relief and dopamine receptors for anti-nausea effects.
Primary Uses: It treats allergies, motion sickness, and nausea/vomiting, and is also used for sedation.
Sedative Effect: Promethazine's ability to cross the blood-brain barrier causes significant drowsiness, distinguishing it from newer antihistamines.
Black Box Warning: Due to the risk of fatal respiratory depression, promethazine should not be used in children under two years old.
Multiple Formulations: Available in tablets, syrup, suppositories, and injections.
Interaction Warnings: It interacts with alcohol and other CNS depressants, increasing the risk of side effects.
Contraindications: Not suitable for all patients, especially those with glaucoma, enlarged prostate, or seizure disorders.

What is Promethazine and How Does It Work?

Promethazine hydrochloride is a first-generation antihistamine derived from phenothiazine. It primarily blocks histamine H1 receptors, which reduces allergy symptoms like itching and sneezing. Additionally, it affects dopamine and acetylcholine, contributing to its anti-nausea effects by acting on the brain's chemoreceptor trigger zone. Its anticholinergic properties also help with nausea, vomiting, and motion sickness.

Unlike newer antihistamines, promethazine crosses the blood-brain barrier, leading to strong sedative and hypnotic effects useful for sedation and sleep. This central nervous system depression is also responsible for common side effects like drowsiness.

Therapeutic Uses of Promethazine

Allergies: Treats seasonal allergic rhinitis, allergic conjunctivitis, urticaria, and angioedema. Its sedative effect helps with severe itching, especially at night.
Nausea and Vomiting: Controls and prevents nausea and vomiting from surgery, chemotherapy, or illness.
Motion Sickness: Prevents and treats motion sickness.
Sedation: Relieves apprehension and induces light sleep before or after surgery, and for short-term insomnia.
Adjunctive Pain Management: Sometimes used with other analgesics for pain.

Potential Side Effects and Warnings

As a CNS depressant, promethazine commonly causes drowsiness, dizziness, confusion, blurred vision, and dry mouth. Patients should avoid driving or operating machinery until they understand the medication's effects. Alcohol and other CNS depressants should be avoided.

A boxed warning highlights the risk of fatal respiratory depression in children under two. It should not be given to infants and used cautiously in older children.

Less common but serious side effects include Neuroleptic Malignant Syndrome, extrapyramidal symptoms, bone marrow depression, and severe tissue injury from injection. Sun sensitivity is also possible.

Promethazine vs. Other Antihistamines

Promethazine's multi-receptor action differs from other antihistamines. The table below compares it to diphenhydramine.


Feature	Promethazine (Phenergan)	Diphenhydramine (Benadryl)
Drug Class	Phenothiazine derivative	Ethanolamine antihistamine
Mechanism	Blocks H1 receptors, dopamine receptors, and acetylcholine.	Primarily blocks H1 receptors.
Primary Uses	Nausea, motion sickness, allergies, sedation.	Allergies, insomnia, motion sickness.
Sedation	Significantly sedating, often prescribed at bedtime.	Sedating, commonly used in over-the-counter sleep aids.
Duration of Effect	Longer-lasting, up to 12+ hours.	Shorter-acting, typically 4-8 hours.
Route of Admin.	Oral tablets, syrups, suppositories, and injections.	Oral capsules, tablets, liquids, and topical creams.
Extrapyramidal Symptoms	Higher risk (rare).	Lower risk.

How to Use Promethazine Safely

Follow your healthcare provider's instructions, using the lowest effective dose for the shortest time. Use a proper measuring device for liquid forms. Inform your doctor and pharmacist about all medications, as interactions can occur with CNS depressants and certain antidepressants. Promethazine is contraindicated in children under two, patients in a coma, or those with known allergies. Use with caution in patients with glaucoma, enlarged prostate, seizure disorders, or heart problems. Overdose symptoms include severe drowsiness, seizures, and respiratory depression, requiring immediate medical attention.

Conclusion

Promethazine is a potent first-generation antihistamine used for allergies, nausea, motion sickness, and sedation. Its ability to cross the blood-brain barrier gives it strong sedative effects, differentiating it from newer antihistamines. However, this also leads to a higher risk of side effects like drowsiness and serious complications, including fatal respiratory depression in young children. Safe use requires strict adherence to prescriptions, awareness of interactions, and understanding warnings. Consult a healthcare provider for diagnosis and treatment. [Disclaimer: This information is for educational purposes only and not a substitute for professional medical advice.]

Frequently Asked Questions

Promethazine is used to treat and prevent allergies (hay fever, conjunctivitis), nausea, vomiting, and motion sickness. Its sedative properties also make it useful for pre- and post-operative sedation and short-term insomnia.

The most common brand name for promethazine is Phenergan. However, it is also available under various other brand names and as a lower-cost generic.

Promethazine is contraindicated in children under two years old due to the risk of fatal respiratory depression. It should be used with caution and careful dosing in children aged two and older, as determined by a doctor.

The most common side effect is drowsiness, but other potential side effects include dizziness, confusion, blurred vision, and dry mouth.

Promethazine is not considered an addictive substance like an opioid, as it doesn't pose a risk of addiction or dependence in the same way. However, it is generally prescribed for short-term use for specific conditions.

Promethazine typically begins to work within 20 minutes of being taken orally. For sleep, it is recommended to take it about 20 to 30 minutes before bed.

No, it is highly recommended to avoid alcohol while taking promethazine. Combining them can significantly increase CNS depression, leading to severe drowsiness, slow breathing, and impaired coordination.

Promethazine is sedating because it can cross the blood-brain barrier and block histamine receptors in the brain, where histamine plays a key role in wakefulness. This action causes feelings of drowsiness and promotes sleep.