How Long Does Withdrawal Take? – A typical withdrawal period lasts around seven days — though some symptoms can last longer. These symptoms can be managed by professionals at a medical detox, which can make individuals feel more comfortable as they move through the withdrawal process.

Addiction specialists typically break up this time into three phases. Phase 1: The first phase lasts 1-4 days, and during this time, physical withdrawal is at its peak. An individual may experience nausea, soreness, headaches, and other uncomfortable symptoms as codeine begins to leave the system. This is also a result of promethazine leaving the system.

The U.S. National Library of Medicine reports that promethazine has a total elimination half-life of 12 hours, which means that its sedative effects will vanish within 24 hours of a person’s last dose. Phase 2: The second stage of withdrawal occurs during days 5-7.

1. At this time, the physical symptoms will begin to fade, and new symptoms will take their place.
2. Instead of feeling sweaty, shaky, or nauseated, an individual may feel fatigued or dehydrated.
3. This is a direct result of the previous four days, and these symptoms often dissipate with appropriate care.
4. Psychological symptoms tend to set in during this stage too.

People who have experienced withdrawal from promethazine and codeine have reported feeling depressed around day five. They have also reported feeling cravings for their drug of choice. Phase 3: The final stage of withdrawal begins on day eight and lasts for some time after, sometimes for as long as 30 days.

How is promethazine cleared?

Summary Promethazine is a first-generation antihistamine used for the treatment of allergic conditions, nausea and vomiting, and motion sickness. Brand Names Phenadoz, Phenergan, Promethazine DM, Promethegan Generic Name Promethazine DrugBank Accession Number DB01069 Background Promethazine, originally known as 3,277 R.P., is an N-dimethylaminopropyl derivative of phenothiazine that was developed in France in 1946.1 Promethazine antagonizes a variety of receptors, allowing it to be used for a number of indications including allergic reactions, pain, sedation, nausea, and vomiting.2, 8, 9, 7, 10 Promethazine was granted FDA approval before 29 March 1951.11, 12 Type Small Molecule Groups Approved, Investigational Structure Weight Average: 284.419 Monoisotopic: 284.13471934 Chemical Formula C 17 H 20 N 2 S Synonyms

• (2-dimethylamino-2-methyl)ethyl-N-dibenzoparathiazine
• 10-(2-Dimethylaminopropyl)phenothiazine
• 10-phenothiazine
• N-(2′-dimethylamino-2′-methyl)ethylphenothiazine
• N,N,alpha-trimethyl-10H-phenothiazine-10-ethanamine
• N,N,α-trimethyl-10H-phenothiazine-10-ethanamine
• Proazamine
• Prometazina
• Promethazine
• Promethazinum

External IDs

Lilly 1516

Indication Promethazine tablets and suppositories are indicated to treat rhinitis, allergic conjunctivitis, allergic reactions to blood or plasma, dermographism, anaphylactic reactions, sedation, nausea, vomiting, pain, motion sickness, and allergic skin reactions.2, 12 Promethazine cough syrup with phenylephrine and codeine is indicated to relieve cough and upper respiratory symptoms, and nasal congestion associated with allergy or the common cold.13 Reduce drug development failure rates Build, train, & validate machine-learning models with evidence-based and structured datasets. Build, train, & validate predictive machine-learning models with structured datasets. Associated Conditions

• Allergic Conjunctivitis (AC)
• Allergic urticaria
• Anaphylaxis
• Cough
• Dermographism
• Motion Sickness
• Nasal Congestion
• Postoperative pain
• Seasonal Allergic Rhinitis
• Vasomotor Rhinitis
• Acute Allergic Reactions
• Dry cough
• Perioperative nausea and vomiting
• Upper respiratory symptoms

Associated Therapies

• Sedative therapy
• Adjunct to anesthesia and analgesia therapy

Contraindications & Blackbox Warnings Avoid life-threatening adverse drug events Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more. Avoid life-threatening adverse drug events & improve clinical decision support.

Absorption A 25mg dose of intramuscular promethazine reaches a C max of 22ng/mL.4 Intravenous promethazine reaches a C max of 10.0ng/mL, with a T max of 4-10h, and an AUC of 14,466ng*h/mL.4 Oral promethazine is only 25% bioavailable due to first pass metabolism.4 Oral promethazine reaches a C max of 2.4-18.0ng/mL, with a T max of 1.5-3h, and an AUC of 11,511ng*h/mL.4 Volume of distribution The volume of distribution of promethazine is approximately 970L or 30L/kg.4 Protein binding Promethazine is 93% protein bound in serum, 5 mostly to albumin.6 Metabolism Promethazine is predominantly metabolized to promethazine sulfoxide, and minorly to desmethylpromethazine and a hydroxy metabolite.3, 4 Hydroxylation of promethazine is predominantly mediated by CYP2D6.3 Hover over products below to view reaction partners Route of elimination An intravenous dose of promethazine is 0.64% eliminated in the urine as the unchanged parent drug, 0.02-2.02% in the urine as desmethylpromethazine, 10% in the urine as promethazine sulfoxide.4 Half-life The elimination half life of promethazine is approximately 12-15h.4 Clearance The intravenous clearance of promethazine is approximately 1.14L/min.4 The renal clearance of promethazine is 5.9mL/min and the renal clearance of promethazine sulfoxide is 90.4mL/min.4 Adverse Effects Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. Improve decision support & research outcomes with our structured adverse effects data.

Pharmacogenomic Effects/ADRs Not Available Drug Interactions This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Food Interactions

Avoid alcohol. Alcohol may increase the sedation caused by promethazine.

Drug product information from 10+ global regions Our datasets provide approved product information including: dosage, form, labeller, route of administration, and marketing period. Access drug product information from over 10 global regions. Product Ingredients

Product Images International/Other Brands Avomine / Fargan / Farganesse / Lergigan / Prothiazine / Receptozine / Romergan Brand Name Prescription Products

Generic Prescription Products

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Unapproved/Other Products

ATC Codes R06AD52 — Promethazine, combinations

• R06AD — Phenothiazine derivatives
• R06A — ANTIHISTAMINES FOR SYSTEMIC USE
• R06 — ANTIHISTAMINES FOR SYSTEMIC USE
• R — RESPIRATORY SYSTEM

D04AA10 — Promethazine

• D04AA — Antihistamines for topical use
• D04A — ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
• D04 — ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
• D — DERMATOLOGICALS

V03AB05 — Prednisolone and promethazine

• V03AB — Antidotes
• V03A — ALL OTHER THERAPEUTIC PRODUCTS
• V03 — ALL OTHER THERAPEUTIC PRODUCTS
• V — VARIOUS

R06AD02 — Promethazine

• R06AD — Phenothiazine derivatives
• R06A — ANTIHISTAMINES FOR SYSTEMIC USE
• R06 — ANTIHISTAMINES FOR SYSTEMIC USE
• R — RESPIRATORY SYSTEM

Drug Categories Chemical Taxonomy Provided by Classyfire Description This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.

Humans and other mammals

UNII FF28EJQ494 CAS number 60-87-7 InChI Key PWWVAXIEGOYWEE-UHFFFAOYSA-N InChI InChI=1S/C17H20N2S/c1-13(18(2)3)12-19-14-8-4-6-10-16(14)20-17-11-7-5-9-15(17)19/h4-11,13H,12H2,1-3H3 IUPAC Name dimethylamine SMILES CC(CN1C2=CC=CC=C2SC2=CC=CC=C12)N(C)C Synthesis Reference US2530451 General References

1. HALPERN BN, HAMBURGER J: A new synthetic anti-histamine substance derived from phenothiazine; phenergan, 3,277 R.P. Can Med Assoc J.1948 Oct;59(4):322-6.
2. Southard BT, Al Khalili Y: Promethazine,
3. Nakamura K, Yokoi T, Inoue K, Shimada N, Ohashi N, Kume T, Kamataki T: CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. Pharmacogenetics.1996 Oct;6(5):449-57.
4. Taylor G, Houston JB, Shaffer J, Mawer G: Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man. Br J Clin Pharmacol.1983 Mar;15(3):287-93. doi: 10.1111/j.1365-2125.1983.tb01501.x.
5. Cantisani C, Ricci S, Grieco T, Paolino G, Faina V, Silvestri E, Calvieri S: Topical promethazine side effects: our experience and review of the literature. Biomed Res Int.2013;2013:151509. doi: 10.1155/2013/151509. Epub 2013 Nov 19.
6. He LL, Wang ZX, Wang YX, Liu XP, Yang YJ, Gao YP, Wang X, Liu B, Wang X: Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques. Colloids Surf B Biointerfaces.2016 Sep 1;145:820-829. doi: 10.1016/j.colsurfb.2016.06.001. Epub 2016 Jun 2.
7. Authors unspecified: Promethazine,
8. Smith HS, Cox LR, Smith BR: Dopamine receptor antagonists. Ann Palliat Med.2012 Jul;1(2):137-42. doi: 10.3978/j.issn.2224-5820.2012.07.09.
9. Adolph O, Koster S, Georgieff M, Georgieff EM, Moulig W, Fohr KJ: Promethazine inhibits NMDA-induced currents – new pharmacological aspects of an old drug. Neuropharmacology.2012 Aug;63(2):280-91. doi: 10.1016/j.neuropharm.2012.03.006. Epub 2012 Apr 7.
10. Flake ZA, Linn BS, Hornecker JR: Practical selection of antiemetics in the ambulatory setting. Am Fam Physician.2015 Mar 1;91(5):293-6.
11. AVERY JL: Treatment of enterobiasis with one oral dose of promethazine hydrochloride. J Am Med Assoc.1956 Jun 23;161(8):681-3. doi: 10.1001/jama.1956.02970080011004.
12. FDA Approved Drug Products: Phenergran Promethazine Oral Tablets (Discontinued)
13. FDA Approved Drug Products: Promethazine with Phenylephrine and Codeine Oral Syrup
14. Cayman Chemical: Promethazine MSDS

External Links Human Metabolome Database HMDB0015202 KEGG Drug D00494 KEGG Compound C07404 PubChem Compound 4927 PubChem Substance 46507798 ChemSpider 4758 BindingDB 50017696 RxNav 8745 ChEBI 8461 ChEMBL CHEMBL643 Therapeutic Targets Database DAP000334 PharmGKB PA451128 RxList RxList Drug Page Drugs.com Drugs.com Drug Page Wikipedia Promethazine FDA label MSDS Clinical Trials

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• Global Pharmaceuticals
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• Hi Tech Pharmacal Co. Inc.
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Dosage Forms

Prices

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only. Patents Not Available State Solid Experimental Properties

Predicted Properties

Predicted ADMET Features

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. ( 23092397 ) Mass Spec (NIST) Download (7.88 KB) Spectra

Does promethazine have codeine in it?

5.2 Life-Threatening Respiratory Depression – Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, including codeine, one of the active ingredients in Promethazine with Codeine Oral Solution. Codeine produces dose-related respiratory depression by directly acting on the brain stem respiratory center that controls respiratory rhythm and may produce irregular and periodic breathing.

Codeine is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to an increased exposure to the active metabolite morphine, Promethazine exerts a depressant effect on the respiratory center that is independent of and additive to that of other respiratory depressants, including codeine,

Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression includes discontinuation of Promethazine with Codeine Oral Solution, close observation, supportive measures, and use of opioid antagonists (eg., naloxone), depending on the patient’s clinical status,

1. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
2. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Promethazine with Codeine Oral Solution, the risk is greatest during the initiation of therapy, when Promethazine with Codeine Oral Solution is used concomitantly with other drugs that may cause respiratory depression, in patients with chronic pulmonary disease or decreased respiratory reserve, and in patients with altered pharmacokinetics or altered clearance (eg., elderly, cachectic, or debilitated patients),

To reduce the risk of respiratory depression, proper dosing of Promethazine with Codeine Oral Solution is essential, Monitor patients closely, especially within the first 24-72 hours of initiating therapy or when used in patients at higher risk. Overdose of codeine in adults has been associated with fatal respiratory depression, and the use of codeine in children younger than 12 years of age has been associated with fatal respiratory depression when used as recommended,

How many hours can you take promethazine?

Dosing – The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

For oral dosage form (tablets):

For allergy symptoms:

Adults and teenagers—12.5 milligrams (mg) before meals and at bedtime; or 25 mg at bedtime as needed. Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 6.25 to 12.5 mg three times a day; or 25 mg at bedtime as needed. Children younger than 2 years of age—Use and dose must be determined by your doctor,

For prevention of motion sickness:

Adults and teenagers—25 mg twice daily; this initial dose should be taken one-half to one hour before traveling. The dose may be repeated eight to twelve hours later if needed. On other days of travel, 25 mg may be taken on arising and again before the evening meal. Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 12.5 to 25 mg one-half to one hour before traveling. The dose may be repeated eight to twelve hours later if needed. Children younger than 2 years of age—Use and dose must be determined by your doctor,

For nausea and vomiting:

Adults and teenagers—25 mg for the first dose, then 12.5 to 25 mg every four to six hours if needed. Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 0.5 mg per pound of body weight (1.1 mg per kg) or 12.5 to 25 mg every four to six hours as needed. Children younger than 2 years of age—Use and dose must be determined by your doctor,

For sedation:

Adults and teenagers—25 to 50 mg. Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 12.5 to 25 mg. Children younger than 2 years of age—Use and dose must be determined by your doctor,

For control of pain or anxiety before or after surgery:

Adults and teenagers—50 mg the night before surgery; 25 to 50 mg after surgery. Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 0.5 mg per pound of body weight (1.1 mg per kg) or 12.5 to 25 mg the night before surgery or after the surgery. Children younger than 2 years of age—Use and dose must be determined by your doctor,

Does promethazine wear off?

How Long Does Withdrawal Take? – A typical withdrawal period lasts around seven days — though some symptoms can last longer. These symptoms can be managed by professionals at a medical detox, which can make individuals feel more comfortable as they move through the withdrawal process.

1. Addiction specialists typically break up this time into three phases.
2. Phase 1: The first phase lasts 1-4 days, and during this time, physical withdrawal is at its peak.
3. An individual may experience nausea, soreness, headaches, and other uncomfortable symptoms as codeine begins to leave the system.
4. This is also a result of promethazine leaving the system.

The U.S. National Library of Medicine reports that promethazine has a total elimination half-life of 12 hours, which means that its sedative effects will vanish within 24 hours of a person’s last dose. Phase 2: The second stage of withdrawal occurs during days 5-7.

1. At this time, the physical symptoms will begin to fade, and new symptoms will take their place.
2. Instead of feeling sweaty, shaky, or nauseated, an individual may feel fatigued or dehydrated.
3. This is a direct result of the previous four days, and these symptoms often dissipate with appropriate care.
4. Psychological symptoms tend to set in during this stage too.

People who have experienced withdrawal from promethazine and codeine have reported feeling depressed around day five. They have also reported feeling cravings for their drug of choice. Phase 3: The final stage of withdrawal begins on day eight and lasts for some time after, sometimes for as long as 30 days.

What is the peak time for promethazine?

3. Absorption, Distribution, Metabolism, Elimination – PM is well absorbed from the gastrointestinal tract. Peak plasma concentrations occur after 2 to 3 hours when promethazine is administered orally (25 to 50 mg) or intramuscularly (25 mg). Following rectal administration of promethazine in a suppository formulation, peak plasma concentrations were observed after about 8 hours.

1. Oral bioavailability is approximately 25%.
2. Rectal bioavailability has been reported at 23%.
3. Promethazine is widely distributed in body tissues and has a large apparent volume of distribution following oral and intramuscular administration.
4. Promethazine has been reported to be 93% protein-bound when determined by gas chromatography and as 76 to 80% protein-bound when determined by HPLC.

Promethazine rapidly crosses the placenta, appearing in the cord blood within 1.5 minutes when given intravenously at term. Promethazine crosses the blood brain barrier. The elimination half-life of promethazine following oral administration has been estimated to be within the range of 12 to 15 hours.

• After intravenous administration of 12.5 mg, blood concentrations of promethazine declined bioexponentially with a terminal elimination half-life of 12 hours,
• PM is metabolized principally to promethazine sulphoxide and to a lesser degree desmethylpromethazine.
• The major site of metabolism is the liver and that the drug is subjected to extensive first-pass hepatic biotransformation, explaining the oral bioavailability of 25%.

Metabolism also occurs in the gut wall but to a lesser degree than earlier postulated. The sulphoxide metabolite has not been detected after intramuscular dosing as circulating levels are probably below analytical detection limits due to a combination of slow absorption, lower dose (50% of oral), and bypass of first-pass metabolism in the liver,

Is promethazine a narcotic?

Technically, no, promethazine is not a narcotic, a term that’s frequently misused, often interchangeably as a reference to any sort of illegal substance.

Does promethazine make you sleepy?

Drowsiness This is one of the most common side effects of promethazine. In fact, promethazine is sometimes used before or after surgeries to help you sleep. Depending on why you’re taking promethazine, you may only need one dose a day. If this is the case, try taking your dose at night to avoid daytime sleepiness.

Does promethazine help with anxiety?

Acute onset of orofacial dystonia from promethazine treatment: A case report A case report a Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine b The Key Laboratory of Mental Disorder’s Management of Zhejiang Province Find articles by

• a Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine
• b The Key Laboratory of Mental Disorder’s Management of Zhejiang Province
• c Brain Research Institute of Zhejiang University, Hangzhou, China.

Find articles by a Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine b The Key Laboratory of Mental Disorder’s Management of Zhejiang Province Find articles by Monitoring Editor: NA. Received 2019 Feb 13; Revised 2019 Aug 30; Accepted 2019 Sep 26.

1. © 2019 the Author(s).
2. Published by Wolters Kluwer Health, Inc.
3. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
4. Promethazine is an antihistamine agent used commonly for nausea and allergy.

Along with its anticholinergic and antidopaminergic functions, promethazine is also used for psychiatric symptoms, such as troubling sleep, anxiety, and agitation. Previous studies have reported that promethazine may occasionally elicit acute dystonia in some individuals, especially for young children and pregnant women.

1. The 68-year-old female patient was admitted to our hospital because of feeling anxious and intermittent palpitation for over 1 year.
2. She developed acute orofacial dystonia following promethazine treatment.
3. Her diagnoses was generalized anxiety disorder.
4. Discontinuation of the offending agent, promethazine, and injection of Botulinum toxin.

The acute orofacial dystonia was finally alleviated by local injection of Botulinum toxin. Careful assessment of the risk of developing acute dystonia is also needed in old patients when initiating the promethazine treatment. Keywords: acute dystonia, Botulinum toxin, promethazine Promethazine, a first-generation antihistamine, is commonly used to treat nausea, allergy, and psychiatric conditions, such as troubling sleep, anxiety, and agitation, due to its sedative function.

• In addition to a strong antagonist of the H1 receptor, promethazine is also a moderate anticholinergic and antidopaminergic agent.
• These pharmacological characteristics made promethazine potentially to cause movement disorders, such as tardive dyskinesia, akathisia, and dystonia.
• Previous studies have reported in children or pregnant women that promethazine is possibly to elicit acute dystonia.

In a woman taking promethazine (25 mg 3 times daily) for controlling hyperemesis gravidarum, the acute orofacial dystonic reaction occurred within 3 days after the treatment was initiated. Other antiemetics, such as metoclopramide and prochlorperazine, can also lead to an acute dystonic reaction.

Compared with metoclopramide, promethazine had a lower rate to cause dystonia when used as intravenous antiemetic therapy. Herein, we present a case of acute onset of orofacial dystonia due to promethazine therapy in an old Chinese woman. A 68-year-old woman was admitted to the Department of Psychiatry in our hospital because of feeling anxious and intermittent palpitation for over 1 year.

In the very beginning, the patient became anxious, upset, and fearful without any known reasons. Meanwhile, she also repetitively felt chest distress, palpitation, and dizziness. Her daily life was severely disturbed, as she lost her interest in square dancing and had poor appetite and sleep quality.

She went to a local hospital and was diagnosed with generalized anxiety disorder. She was prescribed with flupentixol−melitracen (0.5 mg:10 mg in 1 tablet, 3 times daily), paroxetine (20 mg daily), and buspirone (10 mg, three times daily). Her symptoms significantly improved after taking these medications for half a month.

However, this patient then stopped these medications on her own because she perceived herself as well. She soon began to feel uncomfortable again and resumed the treatment, but it did not work as satisfying as before. Consequently, her medications were adjusted to venlafaxine (75 mg daily) with paroxetine and buspirone unchanged.

But her symptoms did not improve. One week before admission, the patient stopped venlafaxine on her own and reused flupentixol−melitracen (1 tablet, 3 times daily), but it also did not help. On admission, her previous history of illnesses was carefully reviewed. She had hypertension for over 20 years and took amlodipine besylate tablet (5 mg daily) to stabilize blood pressure.

She received partial thyroidectomy 10 years ago and took levothyroxine (62.5 μg daily). She denied any history of smoking or drinking or any other illicit substance abuse. Physical examinations did not indicate any abnormal sign. Routine blood test, liver and renal functions, thyroid profiles, tumor markers, and infectious indictors were all normal.

• Electrocardiography, echocardiography, and chest computed tomography were also normal.
• Cranial magnetic resonance imaging revealed ischemic lesions in bilateral basal ganglia and periventricular areas.
• She was again diagnosed with generalized anxiety disorder.
• Flupentixol−melitracen (1 tablet, 3 times daily) was all discontinued and the dose of paroxetine was increased to 30 mg daily.

In addition, a fixed-dose combination of promethazine−chlordiazepoxide tablet (1.25 mg:1.25 mg in 1 tablet, 3 times daily) was added to help control anxiety and aid sleep. However, the 2nd day after taking the promethazine−chlordiazepoxide tablet, this patient developed acute dystonia, which presented as involuntary orofacial movements with slurring speech.

1. Considered as the offending agent, promethazine−chlordiazepoxide was discontinued.
2. Mecobalamine, vitamin E, and clonazepam were added, but the condition did not improve.
3. Paroxetine was then also discontinued and sertraline was initiated and titrated up to 100 mg daily.
4. Neurological consultation agreed with the diagnosis of acute dystonia and recommended the use of Botulinum toxin.

Two months after the onset of orofacial dystonia, the condition was still not alleviated. The patient received injection of Botulinum toxin and the symptoms significantly improved. The Hospital Ethical Committee approved this case study. The patient and her daughter had delivered written informed consent for publication of this case.

• Neuroleptic-induced dystonia usually occurs when the offending drug is initiated or the dosage is increased.
• We report a case of acute orofacial dystonia in an old woman, who started promethazine−chlordiazepoxide treatment for only 1 day.
• The dystonia persisted for 2 months till the injection of Botulinum toxin.

An acute dystonia reaction can occur after exposure to any domapine receptor antagonist, characterized by involuntary contractions of muscles in different body parts. The abnormal movements or postures may present in a sustained or intermittent, reversible or irreversible manner.

• It has reported that 50% of the acute dystonia caused by domapine receptor antagonist occurs with 2 days and 90% occurs within 5 days of initiating the treatment.
• An imbalance of the dopaminergic and cholinergic systems in the basal ganglia is thought to be the major pathophysiological etiology of acute dystonia.

Other researchers also proposed the involvement of the antihistaminic and GABA-ergic systems. Male gender, young age, previous history of acute dystonia, and cocaine use are possible risk factors for acute dystonic reaction. Notably, a “boxed warning” was added to promethazine that in children less than 2 years of age, this drug was contraindicated, and for those older than 2 years of age, a strengthened warning was proposed.

1. To the best of our knowledge, our patient is the oldest among the cases in available literatures.
2. In this patient, there were no apparent risk factors.
3. However, cranial magnetic resonance imaging revealed sporadic ischemic lesions in the bilateral periventricular regions and basal ganglia, indicating possible functional disturbances in these brain regions, which may make the patient susceptible to acute dystonic reaction.

Of note, the patient was previously prescribed with flupentixol−melitracen and took it for a long period. Flupentixol, a typical antipsychotic of the thioxanthene, is mainly used in schizophrenic individuals as a long-acting preparation. Extrapyramidal side effects of flupentixol treatment include dyskinesia, tremor, parkinsonism, and dystonia.

1. Melitracen is a tricyclic antidepressant, but its pharmacology remains largely unknown.
2. Nowadays, flupentixol and melitracen are no longer prescribed alone in clinical practice, but their fixed-dose combination (Deanxit tablet) is still popular in the Chinese market.
3. As an old antipsychotic, flupentixol was also possibly to elicit acute dystonia.

However, the patient had once taken the same dose of flupentixol and discontinued this agent twice, no extrapyramidal side effects were previously observed. It seems unlikely that the acute orofacial dystonia was secondary to the sudden discontinuation of flupentixol−melitracen or the long-term usage of flupentixol.

1. The common recommended treatment for acute dystonia is the administration of diphenhydramine or benztropine intravenously, both of which are anticholinergic agents.
2. It was a pity that our patient did not try any of the aforementioned anticholinergic agents.
3. Benzodiazepines are second-line choice for patients who did not fully respond to anticholinergic therapy.

Indeed, a combination of promethazine−chlordiazepoxide with fixed dose was taken by our patient. Chlordiazepoxide belongs to the benzodiazepine class and has sedative and hypnotic functions. Therefore, it can help to relax skeletal muscle and is unlikely to cause acute dystonia.

1. In addition, local injection of Botulinum toxin is also recommended.
2. In our patient, clonazepam supplement failed to alleviate the dystonic symptoms, which was later improved by Botulinum toxin.
3. To conclude, we report a case of acute onset of orofacial dystonia following promethazine treatment.
4. The patient was an old woman with ischemic changes in the basal ganglia, which may predispose her to acute dystonic condition.

Our case outlines a significant adverse effect of promethazine, which warrants attentions from clinical practitioners when prescribing this medication. The authors thank the patient and her guardian for their understanding to publish this case study.

1. Data curation: Ruili Zhang, Jianbo Lai.
2. Funding acquisition: Jianbo Lai.
3. Investigation: Ruili Zhang, Jianbo Lai.
4. Writing – original draft: Ruili Zhang, Jianbo Lai.
5. Writing – review & editing: Jinwen Huang.

Abbreviations: DRA = domapine receptor antagonist, EPSs = extrapyramidal side effects, GAD = generalized anxiety disorder, MRI = magnetic resonance imaging. How to cite this article: Zhang R, Lai J, Huang J. Acute onset of orofacial dystonia from promethazine treatment. Medicine,2019;98:43(e17675).

• RZ and JL contributed equally to this work.
• Funding: This work was supported by the grants of the National Key Basic Research Program (2016YFC1307100), the Key Research Project of Zhejiang Province (2015C03040), and the National Clinical Research Center for Mental Health Disorders (2015BAI13B02).
• The authors have no conflicts of interest to disclose.

Strenkoski-Nix LC, Ermer J, DeCleene S, et al. Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects, Am J Health Syst Pharm 2000; 57 :1499–505. Seeman P, Watanabe M, Grigoriadis D, et al.

Dopamine D2 receptor binding sites for agonists. A tetrahedral model, Mol Pharmacol 1985; 28 :391–9. Tan PC, Khine PP, Vallikkannu N, et al. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial, Obstet Gynecol 2010; 115 :975–81. DeGrandi T, Simon JE. Promethazine-induced dystonic reaction,

Pediatr Emerg Care 1987; 3 :91–2. Yung CY. Case vignettes of movement disorders, Brain Res Bull 1983; 11 :191–4. Wijemanne S, Jankovic J, Evans RW. Movement disorders from the use of metoclopramide and other antiemetics in the treatment of migraine, Headache 2016; 56 :153–61.

1. Eepers GA, Clappison VJ, Casey DE.
2. Initial anticholinergic prophylaxis for neuroleptic-induced extrapyramidal syndromes,
3. Arch Gen Psychiatry 1983; 40 :1113–7.
4. Sykes DA, Moore H, Stott L, et al.
5. Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors,

Nat Commun 2017; 8 :763. Digby G, Jalini S, Taylor S. Medication-induced acute dystonic reaction: the challenge of diagnosing movement disorders in the intensive care unit, BMJ Case Rep 2015;pii: bcr2014207215. van Harten PN, van Trier JC, Horwitz EH, et al.

1. Cocaine as a risk factor for neuroleptic-induced acute dystonia,
2. J Clin Psychiatry 1998; 59 :128–30.
3. Starke PR, Weaver J, Chowdhury BA.
4. Boxed warning added to promethazine labeling for pediatric use,
5. N Engl J Med 2005; 352 :2653.
6. Lewis K, O’Day CS.
7. Dystonic Reactions.
8. StatPearls,
9. Treasure Island (FL): StatPearls Publishing; 2018.

: Acute onset of orofacial dystonia from promethazine treatment: A case report

What to avoid when taking promethazine?

Promethazine interacts with other medications and substances that cause drowsiness. Examples of these are opioids, BZDs, and alcohol. Promethazine can also interact with anticholinergic medications and MAOIs. It’s a good idea to always provide your healthcare provider and pharmacist with a medication list.

Does promethazine make you feel weird?

2. Key facts –

Do not drink alcohol while taking promethazine. Alcohol increases the risks of side effects.To help you sleep, take promethazine 20 minutes before you go to bed. It normally takes about 30 minutes to work.To prevent motion sickness, take promethazine the night before a long journey or 1 to 2 hours before a short journey.Common side effects of promethazine include drowsiness, headaches, nightmares and feeling dizzy, restless or confused.When promethazine is mixed with other medicines, it’s also known by the brand names Fedril and Night Nurse.

Can promethazine be harmful?

Warnings for other groups – For pregnant women: Promethazine is a category C pregnancy drug. That means two things:

1. Research in animals has shown adverse effects to the fetus when the mother takes the drug.
2. There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should be used only if the potential benefit justifies the potential risk to the fetus. This drug should not be given to a pregnant woman within 2 weeks of delivery because it raises the risk of bleeding in the newborn.

1. For women who are breastfeeding: Promethazine may pass into breast milk and may cause side effects in a child who is breastfed.
2. Talk to your doctor if you breastfeed your child.
3. You may need to decide whether to stop breastfeeding or stop taking this drug.
4. For seniors: Seniors may be more sensitive to the sedating effects of this drug.

They may be more likely to experience severe drowsiness, reduced mental alertness, and confusion. For children:

• This drug should not be used in children younger than 2 years. In children this age, this drug may cause slowed breathing that could be fatal. Caution should also be used when giving this drug to children older than 2 years.
• This drug should not be used in children who are taking other drugs that may cause slowed breathing.
• This drug is not recommended to treat uncomplicated vomiting in children. It should only be used for extended periods of vomiting when the cause is known.
• Some children who have taken this drug at the recommended dosages have had hallucinations and seizures. If children have a temporary illness, such as a cold or the flu, and take this drug, their risk of involuntary muscle contractions increases.
• Excessive large doses of this drug in children may cause sudden death.

All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Is it OK to take 50 mg of promethazine?

PROMETHAZINE HYDROCHLORIDE 50mg Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10- phenothiazine monohydrochloride and has the following structural formula: Promethazine hydrochloride is a racemic compound; the empirical formula is C17H20N2S HCl and its molecular weight is 320.88.

Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is freely soluble in water and soluble in alcohol. Each tablet for oral administration contains 12.5 mg, 25 mg or 50 mg promethazine hydrochloride, USP.

The inactive ingredients include: lactose anhydrous, magnesium stearate, and microcrystalline cellulose. The 50 mg also contains D&C Red # 27 Lake. Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution.

It is thought that this configuration is responsible for its relative lack (1/10 that of chlorpromazine) of dopamine antagonist properties. Promethazine is an H1 receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects. Promethazine is well absorbed from the gastrointestinal tract.

Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours. Promethazine is metabolized by the liver to a variety of compounds; the sulfoxides of promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.

• Promethazine Hydrochloride Tablets are useful for: Perennial and seasonal allergic rhinitis.
• Vasomotor rhinitis.
• Allergic conjunctivitis due to inhalant allergens and foods.
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema.
• Amelioration of allergic reactions to blood or plasma.

Dermographism. Anaphylactic reactions as adjunctive therapy to epinephrine and other standard measures after the acute manifestations have been controlled. Preoperative, postoperative and obstetric sedation. Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery.

• Promethazine Hydrochloride Tablets, USP are contraindicated for use in pediatric patients less than two years of age.
• Promethazine is contraindicated in comatose state, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenthiazines.
• Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma.

Promethazine hydrochloride should not be used in pediatric patients less than 2 years of age because of the potential for fatal respiratory depression. Postmarketing cases of respiratory depression, including fatalities, have been reported with use of promethazine hydrochloride in pediatric patients less than 2 years of age.

1. A wide range of weight-based doses of promethazine hydrochloride have resulted in respiratory depression in these patients.
2. Caution should be exercised when administering promethazine hydrochloride to pediatric patients 2 years of age and older.
3. It is recommended that the lowest effective dose of promethazine hydrochloride be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided.

CNS Depression: Promethazine Hydrochloride Tablets may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine hydrochloride (see PRECAUTIONS, Information for Patients and Drug Interactions).

Respiratory Depression: Promethazine Hydrochloride Tablets, USP may lead to potentially fatal respiratory depression. Use of Promethazine Hydrochloride Tablets, USP in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided. Lower Seizure Threshold: Promethazine Hydrochloride Tablets, USP may lower seizure threshold.

It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold. Bone-Marrow Depression: Promethazine Hydrochloride Tablets, should be used with caution in patients with bone marrow depression.

• Leukopenia and agranulocytosis has been reported, usually when promethazine hydrochloride has been used in association with other known marrow-toxic agents.
• Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine hydrochloride alone or in combination with antipsychotic drugs.

Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated.

• In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS).
• Other important consideration in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of promethazine hydrochloride, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available.

1. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
2. Since reoccurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine hydrochloride should be carefully considered.
3. Use in Pediatric Patients: Promethazine Hydrochloride Tablets, USP are contraindicated for use in pediatric patients less than two years of age.

Caution should be exercised when administering Promethazine Hydrochloride Tablets, USP to pediatric patients 2 years of age and older because of the potential for fatal respiratory depression. Respiratory depression and apnea, sometimes associated with death, are strongly associated with promethazine products and are not directly related to individualized weight-based dosing, which might otherwise permit safe administration.

1. Concomitant administration of promethazine products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients.
2. Antiemetics are not recommended for treatment of uncomplicated vomiting in pediatric patients, and their use should be limited to prolonged vomiting of known etiology.

The extrapyramidal symptoms which can occur secondary to Promethazine Hydrochloride Tablets administration may be confused with the CNS signs of undiagnosed primary disease, e.g., encephalopathy or Reye’s syndrome. The use of Promethazine Hydrochloride Tablets should be avoided in pediatric patients whose signs and symptoms may suggest Reye’s syndrome or other hepatic diseases.

1. Excessively large dosages of antihistamines, including Promethazine Hydrochloride Tablets in pediatric patients may cause sudden death (see OVERDOSAGE).
2. Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients.
3. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine hydrochloride.

Other Considerations: Administration of promethazine hydrochloride has been associated with reported cholestatic jaundice. General Drugs having anticholinergic properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction.

Promethazine Hydrochloride Tablets should be used cautiously in persons with cardiovascular disease or with impairment of liver function. Information for Patients Promethazine Hydrochloride Tablets may cause marked drowsiness or impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery.

The use of alcohol or other central-nervous-system depressants such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers, may enhance impairment (see WARNINGS, CNS Depression and PRECAUTIONS, Drug Interactions).

1. Patients should be advised to report any involuntary muscle movements.
2. Avoid prolonged exposure to the sun.
3. Drug Interactions

CNS Depressants: Promethazine Hydrochloride Tablets may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine hydrochloride.

1. When given concomitantly with Promethazine Hydrochloride Tablets, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half.
2. Dosage must be individualized.
3. Excessive amounts of promethazine hydrochloride relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.

Epinephrine: Because of the potential for promethazine hydrochloride to reverse epinephrine’s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with Promethazine Hydrochloride Tablets overdose. Anticholinergics: Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

• Drug/Laboratory Test Interactions
• The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride:
• Pregnancy Tests: Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.
• Glucose Tolerance Test: An increase in blood glucose has been reported in patients receiving promethazine hydrochloride.
• Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility with this drug. Promethazine was nonmutagenic in the Salmonella test system of Ames.

Pregnancy Teratogenic Effects – Pregnancy Category C: Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine hydrochloride. These doses are from approximately 2.1 to 4.2 times the maximum recommended total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug is prescribed.

Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats. Specific studies to test the action of the drug on parturition, lactation, and development of the animal neonate were not done, but a general preliminary study in rats indicated no effect on these parameters.

1. Promethazine Hydrochloride Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
2. Nonteratogenic Effects: Promethazine administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.
3. Labor and Delivery

Promethazine hydrochloride may be used alone or as an adjunct to narcotic analgesics during labor (see DOSAGE AND ADMINISTRATION). Limited data suggest that use of promethazine hydrochloride during labor and delivery does not have an appreciable effect on the duration of labor or delivery and does not increase the risk of need for intervention in the newborn.

• Pediatric Use
• PROMETHAZINE HYDROCHLORIDE TABLETS, USP ARE CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (See WARNINGS: Black Box Warning and Use in Pediatric Patients).
• Promethazine Hydrochloride Tablets should be used with caution in pediatric patients 2 years of age and older (see WARNINGS: Use in Pediatric Patients).
• Geriatric Use

Clinical studies of promethazine hydrochloride formulations did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of Promethazine Hydrochloride Tablets and observed closely.

Central Nervous System: Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria.

1. Cardiovascular: Increased or decreased blood pressure, tachycardia, bradycardia, faintness.
2. Dermatologic: Dermatitis, photosensitivity, urticaria.
3. Hematologic: Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.
4. Gastrointestinal: Dry mouth, nausea, vomiting, jaundice.

Respiratory: Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal). (See WARNINGS, Respiratory Depression.) Other: Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported.

See WARNINGS, Neuroleptic Malignant Syndrome.) Paradoxical Reactions: Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine hydrochloride. Consideration should be given to the discontinuation of promethazine hydrochloride and to the use of other drugs if these reactions occur.

Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients. Signs and symptoms of overdosage with promethazine hydrochloride range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death.

Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex). Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical-type reaction has been reported in children receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares.

Atropine-like signs and symptoms – dry mouth, fixed, dilated pupils, flushing, as well as gastrointestinal symptoms – may occur. Treatment Treatment of overdosage is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs including respiration, pulse, blood pressure, temperature, and EKG, need to be monitored.

Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Diazepam may be used to control convulsions.

Acidosis and electrolyte losses should be corrected. Note that any depressant effects of promethazine hydrochloride are not reversed by naloxone. Avoid analeptics which may cause convulsions. The treatment of choice for resulting hypotension is administration of intravenous fluids, accompanied by repositioning if indicated.

In the event that vasopressors are considered for the management of severe hypotension which does not respond to intravenous fluids and repositioning, the administration of norepinephrine or phenylephrine should be considered. EPINEPHRINE SHOULD NOT BE USED, since its use in patients with partial adrenergic blockade may further lower the blood pressure.

Extrapyramidal reactions may be treated with anticholinergic antiparkinsonian agents, diphenhydramine, or barbiturates. Oxygen may also be administered. Limited experience with dialysis indicates that it is not helpful. Promethazine Hydrochloride Tablets, USP are contraindicated for children under 2 years of age (see WARNINGS: Black Box Warning and Use in Pediatric Patients).

Allergy: The average oral dose is 25 mg taken before retiring; however, 12.5 mg may be taken before meals and on retiring, if necessary. Single 25 mg doses at bedtime or 6.25 to 12.5 mg taken three times daily will usually suffice. After initiation of treatment, in children or adults, dosage should be adjusted to the smallest amount adequate to relieve symptoms.

The administration of promethazine hydrochloride in 25 mg doses will control minor transfusion reactions of an allergic nature. Motion Sickness: The average adult dose is 25 mg taken twice daily. The initial dose should be taken one-half to one hour before anticipated travel and be repeated eight to twelve hours later if necessary.

1. On succeeding days of travel, it is recommended that 25 mg be given on arising and again before the evening meal.
2. For children, Promethazine Hydrochloride Tablets, syrup, or rectal suppositories, 12.5 to 25 mg, twice daily, may be administered.
3. Nausea and Vomiting: Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see WARNINGS: Use in Pediatric Patients).

The average effective dose of promethazine hydrochloride for the active therapy of nausea and vomiting in children or adults is 25 mg. When oral medication cannot be tolerated, the dose should be given parenterally or by rectal suppository.12.5 to 25 mg doses may be repeated, as necessary, at four- to six-hour intervals.

• For nausea and vomiting in children, the usual dose is 0.5 mg per pound of body weight, and the dose should be adjusted to the age and weight of the patient and the severity of the condition being treated.
• For prophylaxis of nausea and vomiting, as during surgery and the postoperative period, the average dose is 25 mg repeated at four- to six-hour intervals, as necessary.

Sedation: This product relieves apprehension and induces a quiet sleep from which the patient can be easily aroused. Administration of 12.5 to 25 mg promethazine hydrochloride by the oral route or by rectal suppository at bedtime will provide sedation in children.

• Adults usually require 25 to 50 mg for nighttime, presurgical, or obstetrical sedation.
• Pre- and Postoperative Use: Promethazine hydrochloride in 12.5 to 25 mg doses for children and 50 mg doses for adults the night before surgery relieves apprehension and produces a quiet sleep.
• For preoperative medication, children require doses of 0.5 mg per pound of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug.

Usual adult dosage is 50 mg promethazine hydrochloride with an appropriately reduced dose of narcotic or barbiturate and the required amount of a belladonna alkaloid. Postoperative sedation and adjunctive use with analgesics may be obtained by the administration of 12.5 to 25 mg in children and 25 to 50 mg doses in adults.

• Promethazine Hydrochloride Tablets, USP for oral administration are available as:
• 12.5 mg: White to off-white, biconvex, round uncoated tablets, debossed with “AN” and bisect on one side and “745” on the other side
• 25 mg: White to off-white, flat-faced, beveled edge, round, uncoated tablets, debossed with “AN” above “521” with single line bisect separating them on one side and plain on the other side
• Bottles of 1000: NDC 65162-521-11
• 50 mg: Pink color, biconvex, round tablets, debossed with “AN” above “522” on one side and plain on the other side
• Store at 20º to 25°C (68° to 77ºF),
• Dispense in a tight, light-resistant container.
• Distributed by:
• Amneal Pharmaceuticals
• Bridgewater, NJ 08807
• Rev.10-2015-00

1. Revised: 1/2023
2. DIRECT RX

: PROMETHAZINE HYDROCHLORIDE 50mg

What strength is promethazine?

Nausea And Vomiting – Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see WARNINGS – Use in Pediatric Patients ). The average effective dose of promethazine HCl for the active therapy of nausea and vomiting in children or adults is 25 mg.12.5- to 25-mg doses may be repeated, as necessary, at 4- to 6-hour intervals.

Why can’t you take promethazine long term?

Promethazine Side Effects – The most prevalent side effects of promethazine are drowsiness, restlessness and dizziness. Fortunately, most side effects go away within a few weeks after taking the drug. Common side effects of promethazine include:

Atypically happy mood Blurred vision or double vision Difficulty falling or staying asleep Dizziness Drowsiness Dry mouth Hyperactivity Itching Nausea Nervousness Nightmares Stuffy nose Vomiting

Promethazine is also associated with rare long-term side effects, including heart arrhythmias, low blood pressure, liver damage, bone marrow suppression and trouble regulating body temperature. It can also cause skin hyperpigmentation after long-term use, especially on body parts that are exposed to the sun. Serious promethazine side effects include:

Abnormal sweating Abnormal neck or tongue position Confusion Extreme anxiety Faintness Fever Hallucinations Hives Rapid or irregular heartbeat Rash Seizures Slowed or stopped breathing Stiff muscles Swelling of the face, eyes, throat, lips, tongue, hands, feet or ankles Tremors Uncontrolled eye movements Unusual bleeding or bruising Wheezing Yellowed eyes or skin

These serious side effects are rare. Tell your doctor if you experience any of them.

What are the benefits of taking promethazine?

Continuing Education Activity – Promethazine is a medication used to manage and treat allergic conditions, nausea and vomiting, motion sickness, and sedation. It also has off-label uses for nausea and vomiting in pregnancy. Promethazine is a phenothiazine derivative with antidopaminergic, antihistamine, and anticholinergic properties.

This activity reviews the FDA approved-indications, mechanism of action, administration, dosing, adverse drug reactions, contraindications, warning, precautions, monitoring, and toxicity of promethazine. In addition, this activity will highlight the pertinent interprofessional roles of the interprofessional team during the use of promethazine n the treatment of patients with allergic conditions, nausea and vomiting, motion sickness, and related conditions.

Objectives:

Identify the mechanism of action of promethazine. Describe the adverse effects of promethazine. Review the appropriate monitoring for toxicity of promethazine. Summarize interprofessional team strategies for improving care coordination and communication to advance promethazine in patients who present with conditions where it has therapeutic value and can improve outcomes.

Access free multiple choice questions on this topic.

Can I take promethazine after drinking alcohol?

Notes for Consumers: Do not drink alcohol while taking this medication. Drinking alcohol while taking this medication can cause serious side effects, such as central nervous system (CNS) depression, and can increase the risk of falling.

Can you drive off promethazine?

What to avoid – This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

How much promethazine can I take a day?

The typical promethazine dosage for adults with allergies is 25 mg once daily at bedtime. This is because promethazine can make you very drowsy after you take it. An alternative promethazine dosage for allergies is 6.25 mg to 12.5 mg up to 3 times a day. But be aware that you may feel drowsy.

How quickly is promethazine absorbed?

Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours.

What drugs are similar to promethazine?

Antihistamines Phenothiazine antiemetics

5HT3 receptor antagonists

5HT3 receptor antagonists

View all promethazine prices

View all ondansetron prices We could not find an exact match for this medicine. Try searching the Price Guide directly. Get free Discount Card Get free Discount Card Get free Discount Card Dosage Form(s) Available

Injectable solution Oral syrup Oral tablet Rectal suppository

Injectable solution Oral solution Oral tablet Oral tablet, disintegrating

Injectable solution Oral solution Oral tablet

78 major drug interactions (286 brand and generic names) 580 moderate drug interactions (2312 brand and generic names) 14 minor drug interactions (56 brand and generic names)

122 major drug interactions (435 brand and generic names) 212 moderate drug interactions (812 brand and generic names) 4 minor drug interactions (10 brand and generic names)

122 major drug interactions (435 brand and generic names) 212 moderate drug interactions (812 brand and generic names) 4 minor drug interactions (10 brand and generic names)

Ask your doctor before using promethazine together with alcohol. This can cause uncontrollable. View more

Acute alcohol intoxication Cardiovascular disease CNS depression Head injury Antidopaminergic effects 1 Asthma Anticholinergic effects Asthma/COPD Breast cancer Dystonic reactions Hematologic toxicity Liver disease NMS Parkinsonism Renal dysfunction Seizure disorders Tardive dyskinesia Antidopaminergic effects 2

QT interval prolongation Liver disease

QT interval prolongation Liver disease

Side effects Pregnancy warnings Breastfeeding warnings Dosage information Drug images Drug interactions Support group Pricing and coupons

Side effects Pregnancy warnings Breastfeeding warnings Dosage information Drug images Drug interactions Support group Pricing and coupons

Side effects Pregnancy warnings Breastfeeding warnings Dosage information Drug images Drug interactions Support group

Overview Advanced reading

Overview Advanced reading

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Monograph (AHFS) Prescribing information

Monograph (AHFS) Prescribing information

Prescribing information

Light Sedation Allergic Reactions Anaphylaxis Allergic Rhinitis Motion Sickness Nausea/Vomiting Opiate Adjunct Sedation Urticaria Vertigo show all

Nausea/Vomiting Nausea/Vomiting – Chemotherapy Induced Nausea/Vomiting – Postoperative Nausea/Vomiting – Radiation Induced Gastroenteritis Alcohol Use Disorder Obsessive Compulsive Disorder Postanesthetic Shivering Pruritus

Nausea/Vomiting Nausea/Vomiting – Chemotherapy Induced Nausea/Vomiting – Postoperative Nausea/Vomiting – Radiation Induced

What is the pharmacokinetics of promethazine?

Pharmacokinetics of Promethazine Hydrochloride The pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup were studied. The study had an open-label, randomized, crossover design.

At intervals of five to nine days, healthy volunteers were given two 12.5-mg promethazine rectal suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of promethazine oral syrup. Blood samples were collected before each dose and at intervals from 0.5 to 48 hours afterward. Promethazine concentration was determined by high-performance liquid chromatography, and pharmacokinetic values were calculated with noncompartmental methods.

Thirty-six subjects (18 men and 18 women) completed the study. Absorption was highly variable for all the formulations. On average, absorption was more rapid and the maximum plasma concentration (C max ) higher for the syrup than for the suppositories.

1. C max was significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the syrup (19.3 ng/mL).
2. The time to C max (t max ) was significantly shorter for the syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours).
3. There were no significant differences in dose-normalized C max among the three suppository treatments.

Area under the concentration-versus- time curve (AUC) was comparable between the syrup and the 50-mg suppository and between the treatments with two 12.5-mg suppositories and the 25-mg suppository. Elimination profiles were similar among all treatments (mean half-life, 16-19 hours).

There were no significant differences in pharmacokinetics on the basis of sex or race. The mean relative bioavailability for the three suppository treatments ranged from 70% to 97%. Individual relative bioavailabilities ranged from 4% to 343%. The pharmacokinetics of promethazine administered in oral syrup and rectal suppositories were highly variable, but, in general, the suppositories produced a lower C max and later t max than the syrup.

All formulations were comparable in terms of dose-normalized AUC and t 1/2, and the three suppository treatments were comparable in terms of dose-normalized C max, Promethazine hydrochloride is a phenothiazine derivative that is structurally different from the antipsychotic phenothiazines.

1. Promethazine is a histamine H 1 -receptor antagonist with moderate muscarinic dopamine (D 2 )-receptor-blocking effects.
2. Since its introduction in 1946, promethazine has been used in a variety of clinical situations: for the prevention and treatment of nausea and vomiting caused by narcotiC t herapy, migraines, and cancer chemotherapy ; as a sedative, particularly as part of a preoperative drug regimen and during labor ; and for motion sickness.

Promethazine hydrochloride is well absorbed from the gastrointestinal tract, although a significant portion of a dose is subject to first-pass metabolism. Clinical effects are apparent within 20 minutes after oral, rectal, or intramuscular administration, and the effects last four to six hours.

Promethazine undergoes extensive hepatic metabolism to a variety of metabolites. The sulfoxides of promethazine and N -demethylpro-methazine are the predominant metabolites and are excreted in the urine. Negligible amounts of unchanged drug are recovered in the urine. Several studies have evaluated the pharmacokinetics of promethazine hydrochloride administered by different routes.

In a study comparing a 50-mg suppository with oral syrup (50 mg), absorption of both promethazine formulations exhibited pronounced variability, with coefficients of variation greater than 84% for the area under the plasma concentration- versus-time curve (AUC).

• The mean AUC from 0 to 24 hours (AUC 0-24 ) for the suppository was 168 ng x hr/mL, compared with 268 ng x hr/mL for the oral syrup.
• Another study compared a generic promethazine hydrochloride 50-mg suppository with a brand-name preparation of promethazine hydrochloride oral syrup (50 mg) and with a brand-name 50-mg suppository.

Both suppository treatments yielded a lower maximum promethazine concentration and a longer time to maximum promethazine concentration than did the oral syrup. However, there were no significant differences in AUC 0-24, Both suppository treatments and the oral syrup demonstrated high variability with respect to promethazine pharmacokinetics.

The pharmacokinetics of intravenous and oral promethazine have also been compared. On average, 88% of a promethazine dose is absorbed after oral administration; however, the absolute bioavailability is only 25% because of first-pass clearance. This study compared the pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup to healthy subjects.

The study was performed to comply with a regulatory request from the Food and Drug Administration. The specific purpose was to examine the dose proportionality of the three suppository dosage strengths and to assess the bioavailability of promethazine for the three suppository strengths relative to the syrup.

What metabolizes promethazine?

CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. Pharmacogenetics.1996 Oct;6(5):449-57.

Is there an antidote for promethazine?

Toxicity – The main feature of promethazine toxicity is CNS depression, tachycardia, respiratory depression, and delirium. For most overdoses, supportive care and monitoring are the treatment as there is no known antidote. Significant overdoses with profoundly depressed mental status or coma may require airway support, hemodynamic monitoring, and a higher level of care.

• Some studies have shown that early administration of charcoal within 2 hours may be beneficial.
• However, the evidence is still lacking, and further studies are necessary.
• Because promethazine can reverse epinephrine’s vasopressor effect, epinephrine should not be used for hypotension associated with promethazine overdose.

Management of NMS Immediate discontinuation of promethazine, antipsychotic drugs, and other drugs is not essential to concurrent treatment. Intensive symptomatic treatment and medical monitoring Provide treatment for concomitant serious medical problems, where specific treatments are available.

Is promethazine hard on the liver?

Introduction – Promethazine is first generation antihistamine that belongs to the phenothiazine class and is used predominantly as an antiemetic to treat nausea and vomiting and prevent motion sickness. Despite its phenothiazine structure, promethazine has not been linked to instances of clinically apparent acute liver injury.