Diphenhydramine + Phenylephrine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Nasal congestion; Allergic rhinitis; Upper respiratory tract symptoms associated with allergy; Cough Per 5 mL liquid or solution contains diphenhydramine 6.25 mg and phenylephrine 2.5 mg: 20 mL 4 hourly as needed. Max: 6 doses/24 hours. Per 5 mL liquid or solution contains diphenhydramine 12.5 mg and phenylephrine 5 mg: 10 mL 4 hourly as needed. Max: 6 doses/24 hours.
Dosage Details
Oral
Allergic rhinitis, Cough, Nasal congestion, Upper respiratory tract symptoms associated with allergy
Adult: Available preparations:
Diphenhydramine 6.25 mg and phenylephrine 2.5 mg per 5 mL
20 mL 4 hourly as needed. Max: 6 doses per 24 hours.

Diphenhydramine 12.5 mg and phenylephrine 5 mg per 5 mL
10 mL 4 hourly as needed. Max: 6 doses per 24 hours.

Refer to specific product guideline for further information.
Child: Available preparations:
Diphenhydramine 6.25 mg and phenylephrine 2.5 mg per 5 mL
6-11 years 10 mL 4 hourly as needed. Max: 6 doses per 24 hours; ≥12 years Same as adult dose.

Diphenhydramine 12.5 mg and phenylephrine 5 mg per 5 mL
6-11 years 5 mL 4 hourly as needed. Max: 6 doses per 24 hours; ≥12 years Same as adult dose.

Refer to specific product guideline for further information.
Contraindications
Concomitant use with other drugs containing diphenhydramine (including topical preparations) or MAOIs (or within 14 days of use). Lactation.
Special Precautions
Patient with asthma, productive cough, chronic cough (associated with COPD or smoking), diabetes mellitus, CV disease (e.g. ischaemic heart disease, hypertension), genitourinary obstruction, prostatic hyperplasia, pyloroduodenal obstruction (e.g. stenotic peptic ulcer), thyroid dysfunction, increased intraocular pressure or angle-closure glaucoma. Treatment with a cough and cold medicine in children (especially under 12 years old) should be considered carefully due to potential risks and limited evidence on efficacy. Not recommended for use in children below 6 years of age. Pregnancy.
Adverse Reactions
Significant: CNS depression (e.g. drowsiness); excitability in children.
Blood and lymphatic system disorders: Haemolytic anaemia, agranulocytosis, thrombocytopenia.
Cardiac disorders: Chest tightness, palpitations, tachycardia, extrasystoles.
Ear and labyrinth disorders: Tinnitus, labyrinthitis.
Eye disorders: Diplopia, blurred vision.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, xerostomia, dry mucous membranes, epigastric distress.
General disorders and administration site conditions: Fatigue.
Immune system disorders: Anaphylaxis.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Chills.
Nervous system disorders: Headache, ataxia, dizziness, neuritis, paraesthesia, restlessness, sedation, seizure, vertigo, tremor.
Psychiatric disorders: Insomnia, confusion, euphoria, irritability, nervousness.
Renal and urinary disorders: Dysuria, polyuria, early menses, urinary retention.
Respiratory, thoracic and mediastinal disorders: Constriction of the pharynx, thickening of bronchial secretions, wheezing.
Skin and subcutaneous tissue disorders: Diaphoresis, photosensitivity, rash, urticaria.
Patient Counseling Information
This drug may cause CNS depression (e.g. drowsiness), if affected, do not drive or operate machinery.
Drug Interactions
CNS depressant effects may be potentiated by sedatives or tranquilisers.
Potentially Fatal: MAOIs (e.g. selegiline) may enhance the hypertensive effect of phenylephrine.
Food Interaction
Increased CNS depressant effects with alcohol.
Action
Description: Diphenhydramine is a monoethanolamine derivative antihistamine with sedative and antimuscarinic properties. It competes with histamine for H1 receptor sites on effector cells in the blood vessels, gastrointestinal tract, and respiratory tract.
Phenylephrine is a sympathomimetic amine that has a direct effect on α1-adrenergic receptors. It produces vasoconstriction in the nasal mucosa which may help relieve nasal congestion.
Onset: Phenylephrine (nasal decongestant effect): 15-30 minutes.
Duration: Phenylephrine (nasal decongestant effect): ≤4 hours.
Pharmacokinetics:
Absorption: Diphenhydramine: Well absorbed from the gastrointestinal tract. Bioavailability: 42-62%. Time to peak plasma concentration: Approx 1-4 hours.
Phenylephrine: Incomplete and erratic absorption. Bioavailability: ≤38%. Time to peak plasma concentration: 0.75-2 hours.
Distribution: Diphenhydramine: Widely distributed throughout the body, including CNS. Crosses the placenta and enters breast milk. Volume of distribution: 17 L/kg (range: 13-20 L/kg). Plasma protein binding: 98.5%.
Phenylephrine: Volume of distribution: Initial: 26-61 L.
Metabolism: Diphenhydramine: Extensively metabolised in the liver via N-demethylation, mainly by CYP2D6, and in some degree by CYP1A2, 2C9 and 2C19. Undergoes significant first-pass metabolism.
Phenylephrine: Metabolised in the liver via oxidative deamination; undergoes sulfation (mainly in the intestinal wall) and to a lesser extent via glucuronidation to form inactive metabolites. Undergoes first-pass metabolism by monoamine oxidase in the gut and liver.
Excretion: Diphenhydramine: Mainly via urine (as metabolites and in small amounts as unchanged drug). Elimination half-life: 2.4-9.3 hours.
Phenylephrine: Via urine (approx 80%, mainly as inactive metabolites; approx 2.6% as unchanged drug). Elimination half-life: Alpha phase: Approx 5 minutes; terminal phase: 2-3 hours.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Diphenhydramine, CID=3100, https://pubchem.ncbi.nlm.nih.gov/compound/Diphenhydramine (accessed on Jan. 21, 2020)


Chemical Structure Image
Phenylephrine

Source: National Center for Biotechnology Information. PubChem Database. Phenylephrine, CID=6041, https://pubchem.ncbi.nlm.nih.gov/compound/Phenylephrine (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C. Protect from light.
ATC Classification
R06AA52 - diphenhydramine, combinations ; Belongs to the class of aminoalkyl ethers used as systemic antihistamines.
References
Anon. Diphenhydramine (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2020.

Anon. Diphenhydramine and Phenylephrine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2020.

Anon. Diphenhydramine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 24/07/2020.

Anon. Phenylephrine (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2020.

Anon. Phenylephrine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/05/2020.

Buckingham R (ed). Diphenhydramine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2020.

Buckingham R (ed). Phenylephrine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2020.

Cold and Congestion Children’s Nighttime Liquid (Walgreens). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/05/2020.

Cold and Cough Solution (Meijer Distribution Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/05/2020.

Doctor Manzanilla Cough Suppressant and Nasal Decongestant Solution (Mid Valley Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/05/2020.

Disclaimer: This information is independently developed by MIMS based on Diphenhydramine + Phenylephrine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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