(proe METH a zeen)
Allergic conditions, treatment: 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
Nausea and vomiting: Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery; antiemetic therapy in postoperative patients
Motion sickness: Active and prophylactic treatment of motion sickness
Surgical analgesia/hypnotic; pre-/postoperative adjunct: Adjunctive therapy with analgesics and/or anesthesia
Sedation: Preoperative, postoperative, and obstetric sedation; for sedation, relief of apprehension, and production of light sleep from which the patient can be easily aroused
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
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 tissue injury, including gangrene (injection):Promethazine can cause severe chemical irritation and damage to tissues regardless of the route of administration. Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration. Adverse reactions include burning, pain, thrombophlebitis, tissue necrosis, and gangrene. In some cases, surgical intervention, including fasciotomy, skin graft, and/or amputation have been required.
Due to the risks of intravenous (IV) injection, the preferred route of administration of promethazine is deep intramuscular (IM) injection. Subcutaneous injection is contraindicated.
Allergic conditions, treatment:
Oral, rectal: 25 mg at bedtime or 12.5 mg before meals and at bedtime (usual range: 6.25 to 12.5 mg 3 times daily)
IM, IV: 25 mg, may repeat in 2 hours when necessary; switch to oral route as soon as feasible
Motion sickness: Oral, rectal: Initial: 25 mg 30 to 60 minutes before departure; repeat 8 to 12 hours later as needed; maintenance: 25 mg twice daily.
Nausea and vomiting: Oral, IM, IV, rectal: 12.5 to 25 mg every 4 to 6 hours as needed
Obstetrics (labor) analgesia adjunct: IM, IV: Early labor: 50 mg; Established labor: 25 to 75 mg in combination with analgesic at reduced dosage; may repeat every 4 hours for up to 2 additional doses (maximum: 100 mg/day while in labor)
Surgical analgesia/hypnotic; pre-/postoperative adjunct : IM, IV: 25 to 50 mg in combination with analgesic or hypnotic (at reduced dosage)
Sedation: Oral, IM, IV, rectal: 25 to 50 mg/dose
Refer to adult dosing.
Allergic conditions, treatment: Children ≥2 years and Adolescents: Oral: 0.125 mg/kg/dose (maximum dose: 12.5 mg) every 6 hours during the day as needed and 0.5 mg/kg/dose (maximum dose: 25 mg) at bedtime as needed. Note: Not typically a first-line option for allergic conditions; other agents may be more effective with fewer adverse effects.
Motion sickness: Children ≥2 years and Adolescents: Oral, rectal: 0.5 mg/kg/dose (maximum dose: 25 mg) 30 minutes to 1 hour before departure, then every 12 hours as needed (Kleigman 2007)
Nausea and vomiting: Children ≥2 years and Adolescents: Oral, IM, IV, rectal: 0.25 to 1 mg/kg/dose (maximum dose: 25 mg) every 4 to 6 hours as needed (Kliegman 2007) Note: Expert recommendations for postoperative nausea and vomiting (PONV) management do not include promethazine as an option for the prevention or treatment of PONV in pediatric patients; use replaced by newer agents (SAA [Gan 2014]; WHO 2011).
Surgical analgesia/hypnotic; pre-/postoperative adjunct: Children ≥2 years and Adolescents: IM, IV: 0.25 to 1.1 mg/kg once in combination with an analgesic or hypnotic (at reduced dosage; low end of range) and with an atropine-like agent (at appropriate dosage) (Kliegman, 2007). Promethazine dosage should not exceed 12.5 to 25 mg (ie, half of suggested adult dosage).
There are no dosage adjustments provided in the manufacturer 's labeling.
Adults: There are no dosage adjustments provided in the manufacturer 's labeling; use with caution (cholestatic jaundice has been reported with use).
Children ≥2 years and Adolescents: The manufacturer recommends avoiding 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).
Parenteral: IV: Although IV administration should be avoided, promethazine has been administered IV in select patients. Solution for injection may be administered at a maximum concentration of 25 mg/mL; however, to minimize phlebitis further dilution is recommended. Some have suggested further diluting the 25 mg/mL with 10 to 20 mL NS (ISMP 2006).
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: Not for SubQ administration; promethazine is a chemical irritant which may produce necrosis.
IM: Preferred route of administration; administer as a deep IM injection
IV: IV use should be avoided when possible since severe tissue damage has occurred with IV administration; in selected patients, promethazine has been diluted and infused at a maximum rate of 25 mg/minute. To minimize phlebitis, consider administering over 10 to 15 minutes, limiting initial dose to 1/4 or 1/2 the usual dose (eg, in adults 6.25 to 12.5 mg), further diluting the 25 mg/mL strength in 10 to 20 mL NS, and administering through a large bore vein (not hand or wrist) or via a running IV line at port farthest from patients vein (ISMP 2006).
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 and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry cold compresses (Hurst 2004).
Increase dietary intake of riboflavin.
Injection, oral solution, tablets: Store between 20 � �C and 25 � �C (68 � �F and 77 � �F). Protect from light.
Suppositories: Store refrigerated between 2 � �C and 8 � �C (36 � �F and 46 � �F).
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 disodium, phenol, sodium metabisulfite]
Phenergan: 25 mg/mL (1 mL) [pyrogen free; contains edetate 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 (118 mL, 473 mL)
Suppository, Rectal, as hydrochloride:
Phenadoz: 12.5 mg (12 ea); 25 mg (12 ea)
Phenergan: 12.5 mg (12 ea); 25 mg (12 ea); 50 mg (12 ea)
Promethegan: 12.5 mg (12 ea); 25 mg (12 ea, 1000 ea); 50 mg (12 ea)
Generic: 12.5 mg (1 ea, 12 ea); 25 mg (1 ea, 12 ea); 50 mg (12 ea)
Syrup, Oral, as hydrochloride:
Generic: 6.25 mg/5 mL (118 mL, 473 mL)
Tablet, Oral, as hydrochloride:
Generic: 12.5 mg, 25 mg, 50 mg
Stable in D5W, D10W, D5LR, D51/4NS, D51/2NS, D5NS, LR, R, SL.
Y-site administration: Incompatible with aldesleukin, allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, cefotetan, ceftriaxone, dimenhydrinate, doxorubicin liposome, foscarnet, furosemide, hydromorphone, ketamine, morphine, piperacillin/tazobactam.
Compatibility in syringe: Incompatible with cefotetan, ceftriaxone, dexamethasone sodium phosphate, heparin, iodipamide meglumine 52%, iothalamate meglumine 60%, iothalamate sodium 80%, ketorolac, pentobarbital, thiopental.
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Anti-Parkinson Agents (Monoamine Oxidase Inhibitor): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if selegiline or rasagiline is combined with a serotonin modulator. Use of transdermal selegiline with serotonin modulators is contraindicated. Consider therapy modification
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2B6 Inducers (Moderate): May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
EPINEPHrine (Nasal): Promethazine may diminish the vasoconstricting effect of EPINEPHrine (Nasal). Monitor therapy
EPINEPHrine (Oral Inhalation): Promethazine may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Monitor therapy
Epinephrine (Racemic): Promethazine may diminish the vasoconstricting effect of Epinephrine (Racemic). Management: Monitor for diminished vasoconstrictive effects of racemic epinephrine (e.g., diminished efficacy when used for gingival retraction). This interaction is likely of less concern in patients receiving epinephrine for other purposes (e.g., bronchodilation). Monitor therapy
EPINEPHrine (Systemic): Promethazine may diminish the vasoconstricting effect of EPINEPHrine (Systemic). Management: When vasoconstrictive effects are desired in patients receiving promethazine, consider alternatives to epinephrine. Consider use of norepinephrine or phenylephrine, and avoid epinephrine, when treating hypotension associated with promethazine overdose. Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Consider therapy modification
Lumacaftor: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Metoclopramide: May enhance the adverse/toxic effect of Promethazine. Avoid combination
MetyroSINE: May enhance the adverse/toxic effect of Promethazine. Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect 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. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thiotepa: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Zolpidem: CNS Depressants may enhance the CNS depressant effect 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. Consider therapy modification
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 IV administration
Pregnancy tests (hCG-based) may result in false-negatives or false-positives; increased serum glucose may be seen with glucose tolerance tests; may result in false-positives with urine detection of amphetamine/methamphetamine (Melanson 2006); may alter the flare response in intradermal allergen tests (Melanson 2006)
Frequency not defined.
Cardiovascular: Bradycardia, hyper-/hypotension, nonspecific QT changes, orthostatic hypotension, tachycardia,
Central nervous system: Agitation akathisia, catatonic states, confusion, delirium, disorientation, dizziness, drowsiness, dystonias, euphoria, excitation, extrapyramidal symptoms, faintness, fatigue, hallucinations, hysteria, insomnia, lassitude, pseudoparkinsonism, tardive dyskinesia, nervousness, neuroleptic malignant syndrome, nightmares, sedation, seizure, somnolence
Dermatologic: Angioneurotic edema, dermatitis, photosensitivity, skin pigmentation (slate gray), urticaria
Endocrine & metabolic: Amenorrhea, breast engorgement, gynecomastia, hyperglycemia, lactation
Gastrointestinal: Constipation, nausea, vomiting, xerostomia
Genitourinary: Ejaculatory disorder, impotence, urinary retention
Hematologic: Agranulocytosis, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Jaundice
Local: Abscess, distal vessel spasm, gangrene, injection site reactions (burning, edema, erythema, pain), palsies, paralysis, phlebitis, sensory loss, thrombophlebitis, tissue necrosis, venous thrombosis
Neuromuscular & skeletal: Incoordination, tremor
Ocular: Blurred vision, corneal and lenticular changes, diplopia, epithelial keratopathy, pigmentary retinopathy
Otic: Tinnitus
Respiratory: Apnea, asthma, nasal congestion, respiratory depression
Concerns related to adverse effects:
- Altered cardiac conduction: May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines).
- Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, pyloroduodenal obstruction, urinary retention, bladder neck obstruction, BPH, xerostomia, or visual problems.
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
- Extrapyramidal symptoms: May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia.
- Neuroleptic malignant syndrome (NMS): Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.
- Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
- Photosensitivity: May cause photosensitivity; avoid prolonged sun exposure.
- Serious tissue injury: [US Boxed Warning]: Promethazine injection can cause severe tissue injury (including gangrene) regardless of the route of administration. Tissue irritation and damage may result from perivascular extravasation, unintentional intra-arterial administration, and intraneuronal or perineuronal infiltration. In addition to gangrene, adverse events reported include tissue necrosis, abscesses, burning, pain, erythema, edema, severe spasm of distal vessels, phlebitis, thrombophlebitis, venous thrombosis, sensory loss, paralysis, and palsies. Surgical intervention including fasciotomy, skin graft, and/or amputation have been necessary in some cases. The preferred route of administration is by deep intramuscular (IM) injection. Subcutaneous administration is contraindicated. Discontinue intravenous injection immediately with onset of burning and/or pain and evaluate for arterial injection or perivascular extravasation. Although there is no proven successful management of unintentional intra-arterial injection or perivascular extravasation, sympathetic block and heparinization have been used in the acute management of unintentional intra-arterial injection based on results from animal studies. Vesicant; for IV administration (not the preferred route of administration), ensure proper needle or catheter placement prior to and during administration; avoid extravasation.
- 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.
- 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.
- 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); may lead to potentially fatal respiratory depression.
- 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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pediatric: [US Boxed Warning]: Respiratory depression, including fatalities, have been reported in children <2 years of age. Use contraindicated in children <2 years. In children ≥2 years, use the lowest possible dose; other drugs with respiratory depressant effects should be avoided. 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.
- Sodium metabisulfite: Injection may contain sodium metabisulfite; may cause allergic reaction.
C
Adverse effects have not been observed in animal reproduction studies. Promethazine crosses the placenta. Maternal promethazine use has generally not resulted in an increased risk of birth defects. Platelet aggregation may be inhibited in newborns following maternal use of promethazine within 2 weeks of delivery. Promethazine is used for the treatment of nausea and vomiting of pregnancy (refer to current guidelines). Promethazine is also indicated for use during labor for obstetric sedation and may be used alone or as an adjunct to opioid analgesics.
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
Oral: Rapid and complete; large first pass effect limits systemic bioavailability (Sharma, 2003)
Vd: 13.4 � � 3.6 L/kg (Brunton 2011)
Hepatic; hydroxylation via CYP2D6 and N-demethylation via CYP2B6; significant first-pass effect (Sharma, 2003)
Urine, feces as inactive metabolites
Oral, IM: ~20 minutes; IV: ~5 minutes
Maximum serum concentration (Brunton 2011): Oral (syrup): 2.8 � � 1.4 hours; Rectal: 8.2 � � 3.4 hours
Usually 4 to 6 hours (up to 12 hours)
IM: ~10 hours; IV: 9 to 16 hours; Suppositories, syrup: 16 to 19 hours (range: 4 to 34 hours) (Strenkoski-Nox, 2000)
93% (Brunton 2011)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, blurred vision, dry mouth, nausea, vomiting, or insomnia. Have patient report immediately to prescriber signs of infection, bradycardia, tachycardia, abnormal movements, twitching, change in balance, dysphagia, difficulty speaking, severe dizziness, passing out, severe headache, tremors, difficulty moving, rigidity, loss of strength and energy, illogical thinking, hallucinations, mood changes, severe anxiety, tinnitus, seizures, bruising, bleeding, jaundice, vision changes, difficulty breathing, slow breathing, shallow breathing, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot), or severe injection site pain or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.