Version July 2025
Promethazine should not be used in pediatric patients younger than 2 years because of the potential for fatal respiratory depression.
Postmarketing cases of respiratory depression, including fatalities, have been reported with the use of promethazine in pediatric patients younger than 2 years. A wide range of weight-based doses of promethazine have resulted in respiratory depression in these patients.
Exercise caution when administering promethazine to pediatric patients 2 years and older. It is recommended that the lowest effective dose of promethazine be used in pediatric patients 2 years and older and that coadministration with other drugs with respiratory-depressant effects be avoided.
Severe chemical irritation and damage to tissues regardless of the route of parenteral administration has been reported in patients treated with promethazine injection including gangrene, tissue necrosis, and thrombophlebitis; and in some cases, surgical intervention including fasciotomy, skin graft, and/or amputation have been required. The use of promethazine injection by the following routes of administration is contraindicated: intravenous injection at concentrations greater than 1 mg/ml, intra-arterial injection, SUBQ injection. The preferred route of administration is by deep IM administration. Promethazine injection may be administered IV after dilution through an IV catheter inserted in a large vein, preferably through a central venous catheter. If pain occurs at the injection site during IV infusion, immediately discontinue the infusion and evaluate for possible arterial injection or perivascular extravasation, and initiate appropriate medical management.
Dosage guidance:
Safety: Do not administer IV at concentrations >1 mg/mL. IV administration can cause severe tissue damage (eg, necrosis, gangrene) and chemical irritation. If deep IM administration is not possible, can administer IV only after dilution by infusing through an IV catheter inserted in a large vein (not in hand or wrist) and preferably through a central venous catheter.
Motion sickness (alternative agent):
Note: Other therapies may be preferred due to the risk of significant adverse events, including sedation (Ref).
Oral, rectal: Initial: 25 mg 30 to 60 minutes before departure; may repeat 8 to 12 hours later. If needed, may administer 25 mg twice daily on subsequent travel days.
Nausea and/or vomiting, acute:
Note: May use short-term (eg, up to 48 to 72 hours) for self-limiting nausea/vomiting (eg, postoperative rescue therapy, acute vertigo) (Ref).
Oral, rectal: 12.5 to 25 mg every 4 to 6 hours as needed. To avoid intolerable adverse effects, some experts recommend a maximum dose of 50 mg/day (Ref).
IM (preferred alternative route) or IV (alternative route): Note: IV and IM administration is generally avoided due to risk of severe tissue damage and chemical irritation. When parenteral therapy is indicated, other parenteral antiemetics with less risk of tissue injury are preferred (Ref).
12.5 to 25 mg IM or IV every 4 to 6 hours as needed (Barrett 2011; Braude 2008; manufacturer's labeling); for postoperative rescue, may administer 6.25 mg IV as a single dose (Ref). To avoid intolerable adverse effects, some experts recommend a maximum dose of 50 mg/day (Ref).
Nausea and vomiting, pregnancy associated (off-label use):
Note: Safety: IV and IM administration is generally avoided due to risk of severe tissue damage and chemical irritation. When parenteral therapy is indicated, other parenteral antiemetics with less risk of tissue injury are preferred (Ref). Use: May use as add-on therapy when symptoms persist following initial pharmacologic treatment (Ref).
Patients without hypovolemia : Oral, rectal, IM (alternative route): 12.5 to 25 mg every 4 to 6 hours as needed (Ref).
Patients with hypovolemia (alternative agent, alternative route):
Note: Consider for persistent nausea and vomiting in addition to treatment of hypovolemia (eg, IV fluids) (Ref).
IV: 12.5 to 25 mg every 4 to 6 hours (Ref).
Peripartum management, adjunct to opioids:
Note: Other parenteral antiemetics with less risk of tissue injury are preferred (Ref). May be used to potentiate opioid analgesia and decrease side effects (eg, nausea and vomiting) (Ref).
IM (preferred route), IV (alternative route): 25 mg once; may repeat every 4 hours for up to 2 additional doses.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (only 0.6% of an administered dose excreted in the urine unchanged) (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large Vd): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (large Vd): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution (cholestatic jaundice has been reported with use).
Avoid use (Ref).
(For additional information see "Promethazine: Pediatric drug information")
Dosage guidance:
Safety: Use with extreme caution and utilize the lowest effective dose to reduce the risk of adverse effects with all routes of administration. Use has generally been replaced by agents that are more effective with fewer adverse events. Due to risk of severe tissue injury, IV and IM administration is generally avoided.
Nausea and vomiting:
Note: Promethazine has been used as an antiemetic for various presenting conditions (eg, postoperative nausea/vomiting, chemotherapy-induced nausea/vomiting, cyclic vomiting syndrome, migraine). In most clinical situations, routine use has been replaced by alternate agents from other therapeutic classes; however, promethazine may be necessary in refractory situations or as rescue therapy; may consider concomitant diphenhydramine to decrease risk of dystonic adverse effects (Ref).
Children ≥2 years and Adolescents: Oral, IM, IV, rectal: Usual range: 0.25 to 0.5 mg/kg/dose every 4 to 6 hours as needed; doses up to 1.1 mg/kg/dose may be necessary in some patients; do not exceed usual adult dose of 6.25 to 25 mg/dose (Ref).
Preprocedure sedation, adjunct: Children ≥2 years and Adolescents: Oral, IM, IV: 0.5 to 1.1 mg/kg once 30 minutes prior to procedure as part of an appropriate combination regimen; maximum dose: 12.5 to 25 mg/dose; manufacturer recommends in combination with a reduced dose of opioid or barbiturate and an appropriate dosage of an atropine-like drug if appropriate; however, other combination regimens have been described (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.
Children ≥ 2 years and Adolescents: The manufacturer recommends to avoid use in pediatric patients with signs and symptoms of hepatic disease (extrapyramidal symptoms caused by promethazine may be confused with CNS signs of hepatic disease).
Phenothiazines, including promethazine, may cause anticholinergic adverse effects such as blurred vision, confusion, constipation, dry eye, urinary retention, and xerostomia. Promethazine is included in the Beers Criteria of Potentially Inappropriate Medication Use in Older Adults (Ref).
Mechanism: Dose-related; related to the pharmacologic action (ie, muscarinic receptor antagonism) (Ref).
Onset: Rapid; occurs within 1 to 2 hours of administration (Ref).
Risk factors:
• Age ≥65 years (Ref)
• Concurrent use of other anticholinergic agents (Ref)
Promethazine use has been associated with dizziness, drowsiness, delirium, motor dysfunction (motor sensory instability), and sedated state in adult (including pregnant women) (Ref) and pediatric patients (Ref). Promethazine is included in the Beers Criteria of Potentially Inappropriate Medication Use in Older Adults (Ref).
Onset: Rapid; may occur within 30 minutes of ingestion and up to 24 hours after cessation. A delay in cognitive reaction time may be observed within 1 hour of ingestion (Ref).
Risk factors:
• In overdose, ingestion of >250 mg increases risk for delirium (Ref)
• Pediatric patients and older adults (Ref)
• Concurrent use of other CNS depressants (eg, alcohol, opioids) (Ref)
Extrapyramidal reactions (EPS), including akathisia, acute dystonia, drug-induced parkinsonism, and tardive dyskinesia, have occurred with the use of promethazine and other dopamine receptor antagonist neuroleptic agents in adult and pediatric patients (Ref). Symptoms of EPS may be confused with other conditions, such as Reye syndrome or other encephalopathy. Acute akathisia is typically transient and resolves with drug discontinuation, but delayed akathisia may be permanent (Ref). Resolution of acute dystonia occurs quickly after drug discontinuation and with supportive care (Ref). Symptoms of drug-induced parkinsonism typically resolve within 7 months of drug discontinuation but may persist for 18 months or longer (Ref). The use of dopamine receptor antagonists, such as promethazine, may unmask undiagnosed idiopathic Parkinson disease (Ref). Tardive dyskinesia may be irreversible; earlier drug discontinuation increases the likelihood of symptom resolution (Ref).
Mechanism: Dose-related; related to the pharmacologic action (ie, dopamine D2 receptor antagonism leading to imbalance in dopamine and acetylcholine in the striatum) (Ref).
Onset:
• Akathisia: Rapid; usually occurs within the first 72 hours of therapy initiation (data with prochlorperazine) (Ref); however, delayed (tardive) akathisia may occur (Ref).
• Dystonia: Rapid; usually occurs within the first 5 days after therapy initiation or large dose increase (Ref).
• Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within the first month and 90% within the first 3 months of therapy (Ref).
• Tardive dyskinesia: Delayed; symptoms usually occur after at least 3 months of therapy and may occur up to 3 months after therapy discontinuation (Ref).
Risk factors:
• Akathisia
- Age <18 years (increasing with decreasing age) (Ref)
- IV administration (data with prochlorperazine) (Ref)
- Pregnancy (Ref)
• Dystonia
- Age <19 years (increasing with decreasing age) (Ref)
- Males (Ref)
- Use of agents with high dopamine D2 receptor affinity (Ref)
- History of acute dystonia (Ref)
- Underweight or normal body weight (Ref)
- Cocaine use (Ref)
- Pediatric: Acute illness associated with dehydration
• Drug-induced parkinsonism
- Age >60 years (Ref)
- Females (Ref)
- Preexisting movement disorder (Ref)
- Cigarette smoking (Ref)
- Genetic variants (Ref)
• Tardive dyskinesia
- Higher cumulative doses (Ref)
- Longer durations of therapy (Ref)
- Age ≥65 years (Ref)
- Females (Ref)
- Diabetes (Ref)
Neuroleptic malignant syndrome (NMS) has been associated with the use of dopamine receptor antagonist neuroleptics, including promethazine. Recovery generally occurs after drug discontinuation and with supportive care; however, some cases have been fatal (Ref). Cases with promethazine have been reported following single doses, alone or in combination with other medications and has occurred in patients who have previously received promethazine without incident. Resolution onset has occurred 5 to 7 days after diagnosis (Ref).
Mechanism: Non–dose-related; idiosyncratic (Ref).
Onset: Rapid; has been reported within 1 to 2 days (Ref).
Risk factors:
- Higher doses (suggested risk factor, but development of NMS is not dose-dependent) (Ref)
- Rapid dose escalation (Ref)
- Concurrent use of dopamine antagonists may increase risk (Ref)
- Use of agents with high D2 receptor affinity (Ref)
- IV administration (Ref)
- Use of depot formulation (Ref)
- Genetic polymorphism (Ref)
- Catatonia may increase risk (Ref)
Phenothiazines, including promethazine, may cause orthostatic hypotension (Ref). Orthostatic hypotension may increase the risk for falls in older patients; this risk may be augmented by the sedative effects of promethazine.
Mechanism: Dose-related; related to the pharmacologic action (ie, alpha1-adrenergic receptor blockade and anticholinergic effects) (Ref).
Onset: Rapid; may occur immediately following IV infusion or following excessive doses (Ref).
Risk factors:
- Age ≥65 years
- Higher doses
- Parenteral administration
- Concurrent use of thiazide diuretics (Ref)
- Mitral insufficiency
- Pheochromocytoma
Rare but fatal respiratory depression in neonates and children may occur. An FDA black box warning exists for children <2 years of age; however, it may occur in adults, especially patients with compromised respiratory function (Ref).
Mechanism: Unknown; may be due to sedation secondary to H1 antagonism.
Onset: Rapid; can occur within minutes to hours (Ref).
Risk factors:
• Age <2 years
• Excessive doses (Ref)
• Concurrent use of medications that cause respiratory depression (Ref)
• Patients with compromised respiratory function (eg, COPD, sleep apnea)
Unintentional intraarterial administration and perivascular extravasation have been associated with local tissue necrosis and subsequent hand and digit amputation in case reports (Ref). ISMP discourages the use of injectable promethazine (any route) because of the risk of severe tissue damage (Ref).
Mechanism: Non–dose-related; the acidic pH (4 to 5.5) of promethazine induces cellular and tissue necrosis, leading to complications such as inflammation, vasoconstriction, and thrombosis (Ref).
Onset: Varied; pain during IV infusion can occur during administration. Skin discoloration and tissue necrosis have occurred immediately following injection and up to 2 weeks after administration (Ref).
Risk factors:
• Dehydration may make IV access challenging, increasing the risk for extravasation (Ref)
• Concentrations >25 mg/mL and rapid administration (<10 minutes) increase the risk for extravasation (Ref)
• Intraarterial administration increases the likelihood of necrosis and amputation (Ref)
• IV placement in small veins (eg, hand and wrist) increases the risk for inadvertent intraarterial administration (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Cardiovascular: Bradycardia, decreased blood pressure, local thrombophlebitis (injection), localized phlebitis (injection), peripheral vasospasm (injection), venous thrombosis (injection)
Dermatologic: Dermatitis, skin photosensitivity, urticaria
Gastrointestinal: Nausea, vomiting
Hematologic & oncologic: Immune thrombocytopenia, leukopenia, thrombocytopenia
Hepatic: Cholestatic jaundice, jaundice
Hypersensitivity: Angioedema
Local: Abscess at injection site, erythema at injection site, swelling at injection site
Nervous system: Abnormal sensory symptoms (injection), ataxia, catatonia, disorientation, euphoria, excitement, fatigue, hysteria, insomnia, lassitude, nervousness, paralysis (injection), sedated state, seizure
Neuromuscular & skeletal: Tremor
Ophthalmic: Blurred vision, diplopia
Otic: Tinnitus
Respiratory: Apnea, asthma, nasal congestion
Postmarketing:
Cardiovascular: Increased blood pressure (Tsay 2015), orthostatic hypotension (Shi 2011), tachycardia (Tsay 2015)
Dermatologic: Gangrene of skin and/or other subcutaneous tissues (injection) (Keene 2006)
Gastrointestinal: Xerostomia (Brown 1997)
Hematologic & oncologic: Agranulocytosis
Local: Burning sensation at injection site (Keene 2006), local tissue necrosis (injection) (Keene 2006), pain at injection site (Keene 2006)
Nervous system: Agitation (Tsay 2015), confusion (Tsay 2015), delirium (Page 2009), dizziness (Brown 1997), drowsiness (Naicker 2013), extrapyramidal reaction (Musco 2019), hallucination (Tsay 2015), hyperexcitability, motor dysfunction (Kavanagh 2012), neuroleptic malignant syndrome (Mendhekar 2005), nightmares, slurred speech (Tsay 2015)
Respiratory: Respiratory depression (Tsay 2015)
Hypersensitivity or idiosyncratic reaction to promethazine, other phenothiazines, or any component of the formulation; coma; treatment of lower respiratory tract symptoms, including asthma; children <2 years of age; intra-arterial or subcutaneous administration; IV administration at concentrations >1 mg/mL.
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines).
• Photosensitivity: May cause photosensitivity; avoid prolonged sun exposure.
• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.
Disease-related concerns:
• Bone marrow suppression: Use with caution in patients with bone marrow suppression; leukopenia and agranulocytosis have been reported.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease.
• GI motility: Use with caution in patients with decreased GI motility or pyloroduodenal obstruction as anticholinergic effects may exacerbate underlying condition.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade.
• Hepatic impairment: Use with caution in patients with hepatic impairment; cholestatic jaundice has been reported with use. Avoid use in pediatric patients with signs and symptoms of hepatic disease (extrapyramidal symptoms caused by promethazine may be confused with CNS signs of hepatic disease).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; condition may be exacerbated by cholinergic blockade.
• Ophthalmic conditions: Use with caution in patients with certain ophthalmic conditions (eg, narrow angle glaucoma, visual problems) as anticholinergic effects may exacerbate underlying condition.
• Parkinson disease: Use with caution in patients with Parkinson disease; may have increased risk of tardive dyskinesia.
• Respiratory disease: Avoid use in patients with compromised respiratory function or in patients at risk for respiratory failure (eg, COPD, sleep apnea).
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
• Urinary tract conditions: Use with caution in patients with urinary retention, benign prostatic hyperplasia (BPH), or bladder neck obstruction, as anticholinergic effects may exacerbate underlying condition.
Special populations:
• Pediatric: Antiemetics are not recommended for the treatment of uncomplicated vomiting in pediatric patients; limit use to prolonged vomiting of known etiology. Avoid use in children who may have Reye syndrome or hepatic disease as adverse reactions caused by promethazine may be confused with signs of primary disease.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Ethanol: Oral solution contains 7% ethyl alcohol.
• Sodium metabisulfite: Injection may contain sodium metabisulfite; may cause allergic reaction.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as hydrochloride:
Phenergan: 50 mg/mL (1 mL) [contains edetate (edta) disodium, phenol, sodium metabisulfite]
Phenergan: 25 mg/mL (1 mL) [pyrogen free; contains edetate (edta) disodium, phenol, sodium metabisulfite]
Generic: 25 mg/mL (1 mL); 50 mg/mL (1 mL)
Solution, Oral, as hydrochloride:
Generic: 6.25 mg/5 mL (5 mL, 120 mL, 473 mL); 12.5 mg/10 mL (10 mL)
Suppository, Rectal, as hydrochloride:
Promethegan: 12.5 mg (1 ea, 12 ea); 25 mg (12 ea); 50 mg (1 ea, 12 ea)
Generic: 12.5 mg (1 ea, 12 ea); 25 mg (1 ea, 12 ea)
Tablet, Oral, as hydrochloride:
Generic: 12.5 mg, 25 mg, 50 mg
Yes
Solution (Phenergan Injection)
25 mg/mL (per mL): $4.04
50 mg/mL (per mL): $5.60
Solution (Promethazine HCl Injection)
25 mg/mL (per mL): $2.09 - $2.50
50 mg/mL (per mL): $3.02 - $4.62
Solution (Promethazine HCl Oral)
6.25 mg/5 mL (per mL): $0.10 - $1.27
Suppository (Promethazine HCl Rectal)
12.5 mg (per each): $15.93 - $17.71
25 mg (per each): $15.93 - $17.71
Suppository (Promethegan Rectal)
12.5 mg (per each): $17.71
25 mg (per each): $17.71
50 mg (per each): $35.77
Tablets (Promethazine HCl Oral)
12.5 mg (per each): $0.49
25 mg (per each): $0.10 - $0.51
50 mg (per each): $0.78
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer with food, water, or milk to decrease GI distress. Measure and administer prescribed dose of oral solution using dosing syringe, dosing spoon, or dosing cup.
Parenteral: The Institute for Safe Medication Practices does not recommend the use of injectable promethazine (any route) due to the risk of severe tissue damage (Ref). Do not administer IV at concentrations >1 mg/mL; may cause severe tissue damage (eg, necrosis, gangrene) and chemical irritation. Not for SUBQ administration.
IM: Administer as a deep IM injection.
IV: Administer IV only if IM injection not possible; dilution is required for IV administration; infuse through an IV catheter inserted in a large vein (not in hand or wrist) and preferably through a central venous catheter. Due to risk of severe tissue damage, dilute to a concentration ≤1 mg/mL and infuse over 20 to 40 minutes. Maximum rate of infusion: 2.5 mL/minute if diluted in 50 mL or 5 mL/minute if diluted in 100 mL (Ref).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Discontinue immediately if burning or pain occurs with administration; evaluate for inadvertent arterial injection or extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately; leave cannula/needle in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/cannula; elevate extremity. Information conflicts regarding the use of dry warm or dry cold compresses. May consider hyaluronidase antidote for refractory cases in addition to supportive management (Ref).
Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as five separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).
Oral: Measure and administer prescribed dose of oral solution using dosing syringe, dosing spoon, or dosing cup.
Parenteral:
Note: The Institute for Safe Medication Practices recommends against the use of injectable promethazine (any route) due to the risk of severe tissue damage (Ref).
IM: Administer as a deep IM injection.
IV: IV administration should be avoided due to risk for severe tissue damage. If used, promethazine should be administered diluted at a concentration ≤1 mg/mL and infused over 20 to 40 minutes at a maximum rate of 1.25 mL/minute. Administer through an IV catheter in a large bore vein (not in hand or wrist) or via a running IV line at port farthest from patient's vein; central venous catheter is preferred (Ref).
SUBQ: Do not administer by SUBQ injection; may result in tissue necrosis.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Discontinue immediately if burning or pain occurs with administration; evaluate for inadvertent arterial injection or extravasation (Ref). If extravasation occurs, stop infusion immediately; leave cannula/needle in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/cannula unless needed for IV antidote; elevate extremity; apply dry, warm compresses; may consider hyaluronidase for refractory cases in addition to supportive management (Ref).
Motion sickness: Prophylaxis and treatment of motion sickness.
Nausea and/or vomiting, acute: Prevention and control of nausea and/or vomiting.
Peripartum management, adjunct to opioids: May be used to potentiate opioid analgesia.
Pregnancy-associated nausea and vomiting
Promethazine may be confused with chlorproMAZINE, predniSONE
Phenergan may be confused with PHENobarbital, Phrenilin, Theragran
The Institute for Safe Medication Practices (ISMP) includes this medication (injectable formulation) among its list of drugs which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings). ISMP strongly discourages use of injectable promethazine (any route) and suggests facilities remove from all areas (including pharmacy) and not allow practitioners to order (ISMP 2020; ISMP 2024).
Beers Criteria: Promethazine, a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).
Promethazine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of recurrent falls due to an increased risk of falls. Some disease states of concern include QTc prolongation, dementia and delirium (O’Mahony 2023).
KIDs List: Dopamine antagonists, when used in pediatric patients <18 years of age, are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided in infants and used with caution in children and adolescents due to risk of acute dystonia (dyskinesia), and with intravenous administration an increased risk of respiratory depression, extravasation, and death (strong recommendation; moderate quality of evidence) (PPA [Meyers 2020]).
Sominex: Brand name for promethazine in Great Britain, but also is a brand name for diphenhydrAMINE in the US
Substrate of CYP2B6 (Minor), CYP2D6 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Promethazine. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Promethazine. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Chlorprothixene. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider Therapy Modification
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
EPINEPHrine (Systemic): Promethazine may decrease vasoconstricting effects of EPINEPHrine (Systemic). Management: Avoid epinephrine and consider norepinephrine or phenylephrine when treating hypotension due to promethazine overdose. Consider alternative vasocontrictors in patients treated with promethazine. This combination may be indicated in anaphylaxis treatment. Risk D: Consider Therapy Modification
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Haloperidol: Promethazine may increase anticholinergic effects of Haloperidol. Promethazine may increase CNS depressant effects of Haloperidol. Promethazine may increase serum concentration of Haloperidol. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Metoclopramide: May increase adverse/toxic effects of Promethazine. Risk X: Avoid
MetyroSINE: May increase adverse/toxic effects of Promethazine. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pitolisant: Promethazine may decrease therapeutic effects of Pitolisant. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider Therapy Modification
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Tranylcypromine: May increase anticholinergic effects of Antihistamines, First Generation. Risk X: Avoid
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Use of promethazine may result in false-negative or false-positive hCG-based pregnancy tests.
Promethazine crosses the placenta (Potts 1961).
Outcome data following maternal use of promethazine during pregnancy are available (Asker 2005; Bártfai 2008; Etwel 2017; Hansen 2020; Larrimer 2014; Schrager 2023). Platelet aggregation may be inhibited in newborns following maternal use of promethazine within 2 weeks of delivery.
Promethazine is indicated for use during labor for obstetric sedation and may be used alone or as an adjunct to opioid analgesics. Promethazine may be used as adjunctive therapy in the management of nausea and vomiting of pregnancy when the preferred agents do not provide initial symptom improvement or when symptoms persist despite other therapies (ACOG 189 2018).
It is not known if promethazine is present in breast milk.
Drowsiness and irritability have been reported in breastfed infants exposed to other antihistamines (Ito 1993).
Antihistamines may decrease maternal serum prolactin concentrations when administered prior to the establishment of lactation. This effect was observed following the injection of promethazine to patients on their first postpartum day prior to the initiation of breastfeeding (Messinis 1985).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. Single maternal doses of promethazine may be compatible with breastfeeding; repeated doses should be avoided (WHO 2002). Use of a second-generation antihistamine is preferred when an oral antihistamine is needed in lactating patients. Infants exposed to a first-generation antihistamine via breast milk should be monitored for irritability, jitteriness, or drowsiness (Butler 2014, WHO 2002).
Increase dietary intake of riboflavin.
Relief of symptoms; mental status and CNS effects (including sedation, akathisia, delirium, extrapyramidal symptoms); signs and symptoms of tissue injury (burning or pain at injection site, phlebitis, edema) with parenteral administration.
Phenothiazine derivative; blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; competes with histamine for the H1-receptor; muscarinic-blocking effect may be responsible for antiemetic activity; reduces stimuli to the brainstem reticular system
Onset of action: Oral, IM: ~20 minutes; IV: ~5 minutes
Duration: Usually 4 to 6 hours (up to 12 hours)
Absorption: Oral: Rapid and complete; large first pass effect limits systemic bioavailability (Sharma 2003)
Distribution: Vd: 13.4 ± 3.6 L/kg (Brunton 2011)
Protein binding: 93% (Brunton 2011)
Metabolism: Hepatic; hydroxylation via CYP2D6 and N-demethylation via CYP2B6; significant first-pass effect (Sharma 2003)
Bioavailability: Oral: ~25% (Sharma 2003); Rectal: 21.7% to 23.4% (Brunton 2011)
Half-life elimination: IM: ~10 hours; IV: 9 to 16 hours; Suppositories, syrup: 16 to 19 hours (range: 4 to 34 hours) (Strenkoski-Nix 2000)
Time to maximum serum concentration (Brunton 2011): Oral (syrup): 2.8 ± 1.4 hours; Rectal: 8.2 ± 3.4 hours
Excretion: Urine, feces as inactive metabolites
