This grade answers one narrow question: how strong is the public evidence and safety record behind this drug, and how clean is its money trail and court record? It is not a verdict on whether the drug is right for you.
This verdict covers injectable promethazine, not every form of the drug, so it does not affect the grade.
Injectable promethazine, an antihistamine used to treat severe urticaria, can cause thrombosis, skin necrosis and gangrene following extravasation or accidental injection into an artery ( Prescrire Int n° 109). Injectable dexchlorpheniramine, which does not appear to carry these risks, is a better option.
Prescrire is a French independent review funded only by subscribers, with no industry money. Its annual "drugs to avoid" list (2026 edition, section: Allergy) names drugs it judges more harmful than useful in every authorised indication. Its view is one expert opinion, reached without a conflict of interest.
INDICATIONS AND USAGE Promethazine is useful for: Perennial and seasonal allergic rhinitis. Vasomotor rhinitis. Allergic conjunctivitis due to inhalant allergens and foods. Mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Amelioration of allergic reactions to blood or plasma. Dermographism. Anaphylactic reactions, as adjunctive therapy to epinephrine and other standard measures, after the acute manifestations have been controlled. Preoperative, postoperative, or obstetric sedation. Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery. Therapy adjunctive to meperidine or other analgesics for control of post-operative pain. Sedation in both children and adults, as well as relief of apprehension and production of light sleep from which the patient can be easily aroused. Active and prophylactic treatment of motion sickness. Antiemetic therapy in postoperative patients.
CONTRAINDICATIONS Promethazine Syrup is contraindicated for use in pediatric patients less than two years of age. Promethazine Syrup is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma.
WARNINGS PROMETHAZINE SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS. CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED. CNS Depression Promethazine Syrup may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore ...
ADVERSE REACTIONS Central Nervous System Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported. Cardiovascular -Increased or decreased blood pressure, tachycardia, bradycardia, faintness. Dermatologic -Dermatitis, photosensitivity, urticaria. Hematologic -Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis. Gastrointestinal -Dry mouth, nausea, vomiting, jaundice. Respiratory -Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal). (See WARNINGS-Respiratory Depression .) Other -Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. (See WARNINGS-Neuroleptic Malignant Syndrome .) Paradoxical Reactions Hyperexcitability and abnormal movements have been reported in patients following a single administration of prome...
Source: FDA SPL label for PROMETHAZINE HYDROCHLORIDE (Xttrium Laboratories, Inc.), effective 20250407. Full label on DailyMed.
These are counts of reports people filed, not rates of harm. Anyone can file one, and nobody checks whether the drug was the cause. Millions of doses are taken for every report sent, so the useful part is how this drug compares with the average across all drugs.
| 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 |
|---|---|---|---|---|---|---|---|
| 5,958 | 4,547 | 2,789 | 2,320 | 2,206 | 2,411 | 2,210 | 1,088 |
4,271 reports blaming this drug for every million Medicare prescriptions filled, which is 1.5× the typical drug on this site. (5,651 reports in 2024–2026, against 1,323,113 Medicare fills in one year. This is the one number here that accounts for how many people take the drug.)
Source: the FDA's Adverse Event Reporting System (FAERS). Reports are voluntary and unverified. Drugs that are prescribed a lot, in the news, or in lawsuits attract more reports, so the percentages are compared with the whole database to correct for that partly, not fully.
| Date | Class | Firm | Reason |
|---|---|---|---|
| 05/2014 | Class II | Zydus Pharmaceuticals USA Inc | Presence of Foreign Tablets: Presence of atenolol 25 mg tablet mixed into promethazine 25 mg tablet bottles. |
Class I = reasonable probability of serious harm. Class II = temporary or reversible harm. Class III = unlikely to harm. Most generic recalls are manufacturing or labeling defects for one lot, not a verdict on the molecule.
Counts measure how much evidence exists and how transparent it is, not how big the benefit is. For that, ask your prescriber: if 100 people like me took this, how many would get better because of it, and how many would be harmed? (Doctors call these the "number needed to treat" and "number needed to harm.") It differs by condition and is the number drug ads leave out. Sources: PubMed, ClinicalTrials.gov.
In 2024, drug companies reported $0 in payments to US physicians and hospitals tied to this drug across 0 transactions.
No pending federal MDL names this drug or its brands.
Not named in any federal pharmaceutical settlement of $100M or more on record.
Sources: CMS Open Payments (Sunshine Act); Judicial Panel on Multidistrict Litigation pending docket list; DOJ settlements as tabulated on Wikipedia with links to the primary record. State-court and individual suits are not included.
| Product | Fills | $/fill |
|---|---|---|
| Promethazine HCl | 1,304,504 | $10 |
| Promethegan | 18,532 | $104 |
| Phenergan | 77 | $72 |
Same ATC pharmacological class, graded ones first, best grade at the top. Being in the same class does not make them interchangeable for your condition; it makes them worth asking about.