Doxylamine vs. Diphenhydramine: Similarities and Differences
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Medically reviewed by Mary Choy, PharmD
Doxylamine and diphenhydramine are Food and Drug Administration (FDA) approved antihistamines used to treat insomnia, motion sickness, hay fever, and common cold symptoms, among other uses.
As commonly used medications, doxylamine and diphenhydramine, administered to adults and children, are available in generic and brand-name forms.
Most brand-name forms of doxylamine and diphenhydramine are available over-the-counter (OTC). However, some are given on prescription by a healthcare provider.
While viewed as similar, doxylamine and diphenhydramine contain notable differences; for example, doxylamine stays in your system longer than diphenhydramine. Therefore, it may be more likely to cause next-day drowsiness as it takes the body roughly 20 hours to expel the dose.
This article will provide an in-depth comparison of doxylamine and diphenhydramine, reviewing their similarities and differences in uses, dosing requirements, potential side effects, and efficacy.
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Antihistamines and Allergy Relief
The following outlines the role of antihistamines in relieving allergy symptoms, a primary use of doxylamine versus diphenhydramine.
What Are Antihistamines?
Antihistamines temporarily relieve the symptoms of hay fever or other upper respiratory allergies.
Allergic reactions are caused by histamine release from the immune system in response to an allergen.
Allergy Symptoms
Allergy symptoms include nasal congestion, redness of the eyes, sneezing, coughing, runny nose, and swollen lymph nodes.
How They Work
Antihistamines bind (also known as their mechanism of action) to histamine receptors on the surface of cells, such as airways and other smooth muscles.
This process blocks the effects of histamines and alleviates allergy symptoms.
Forms of Administration
OTC Antihistamines are typically available as swallowable tablets, capsules, liquid suspensions, nasal sprays, and eye drops.
Conversely, antihistamines can given in prescription form as injectable (intravenous [IV] or intramuscular) medications (administered in healthcare settings).
Examples of common brand-name antihistamines include Zyrtec (cetirizine), Clarinex (desloratadine), Allegra (fexofenadine), Xyzal (levocetirizine), and Claritin (loratadine).
What Is Doxylamine?
Doxylamine is an orally administered antihistamine used to treat insomnia and allergy symptoms that is approved for use in adults and children 12 years and older.
To treat insomnia, doxylamine is available as an orally administered tablet.
Comparatively, doxylamine is used alongside other medications, such as a liquid and liquid-filled capsule, to treat allergy symptoms.
Doxylamine is often combined with decongestants and other active ingredients, such as acetaminophen and phenylephrine, to relieve allergy symptoms.
Brand-Name Forms
Common OTC-branded forms of doxylamine for allergy relief include:
Alka-Seltzer Plus (aspirin/dextromethorphan/doxylamine/phenylephrine)
Common OTC-branded forms of doxylamine for the treatment of insomnia include:
Unisom Sleeptabs (doxylamine succinate)
Sleep Aid (doxylamine hydrochloride)
Beyond OTC options, prescribed (Rx) doxylamine succinate with pyridoxine, brand-name Bonjesta is approved as a first-line treatment of nausea and vomiting during pregnancy.
Forms of Administration
Doxylamine, an active ingredient in various products, is available in varying dosage forms, such as extended-release (ER) tablets, immediate-release (IR) tablets, liquid solutions, and liquid-filled capsules.
How It Works
Doxylamine works by blocking the action of histamine by attaching to the histamine receptors. This effect can relieve allergy symptoms.
What Is Diphenhydramine?
Diphenhydramine is an FDA-approved antihistamine that treats allergy symptoms, eczema, urticaria (hives), and insect bites.
Age requirements to use diphenhydramine vary depending on the specific branded product used, though generally, diphenhydramine is not encouraged for use in children under 4 years old.
Diphenhydramine comes as a rapidly disintegrating (dissolving) tablet, a capsule, a liquid-filled capsule, a dissolving strip, powder, and a liquid to take by mouth.
However, an intravenous (IV) injectable form of diphenhydramine is available to treat allergic reactions, especially for people who are unable to take it orally.
OTC Diphenhydramine is available as monotherapy (single-ingredient product) or in combination with other drugs.
Brand-Name Forms
Common OTC-branded forms of diphenhydramine for allergy relief include:
Benadryl (diphenhydramine hydrochloride)
Sudafed PE Severe Cold (acetaminophen, diphenhydramine, phenylephrine)
Robitussin Nighttime Cough and Cold (diphenhydramine, phenylephrine)
Benadryl-D Allergy Plus Sinus (diphenhydramine, phenylephrine)
Common OTC-branded forms of diphenhydramine for motion sickness include:
Dramamine (diphenhydramine hydrochloride)
Common OTC-branded forms of diphenhydramine for insomnia (diphenhydramine should not be used to cause sleepiness in children younger than 12 years old) include:
Nytol (diphenhydramine hydrochloride)
Tylenol PM (acetaminophen/diphenhydramine hydrochloride)
Sominex Max (diphenhydramine hydrochloride)
Diphenhydramine in Parkinson's Disease
Diphenhydramine is a drug of choice to help control abnormal movements in people who have stage Parkinson's disease (PD) or movement problems caused by a medication side effect, such as tardive dyskinesia (TD).
Forms of Administration
Diphenhydramine, an active ingredient in various products, is available in multiple oral dosage forms, including tablets, film-coated tablets, rapidly disintegrating (dissolving) tablets, capsules, dissolving strips, powder, and liquid suspension forms.
It is also available as an intramuscular or IV (intravenous, into a vein) injection.
How It Works
Like doxylamine, diphenhydramine works by blocking the action of histamine.
Summary of Notable Differences
Doxylamine and diphenhydramine belong to the same class of drugs and share the exact mechanism of action.
Both are FDA-approved for treating insomnia, hay fever, and allergy symptoms.
Apart from many similarities, however, doxylamine and diphenhydramine carry some notable differences, including the following:
Diphenhydramine is used alone or with other drugs for allergic reactions or hay fever. On the contrary, doxylamine is only used in combination with other decongestants or painkillers, etc.
Doxylamine causes more drowsiness than diphenhydramine. It is as effective as diphenhydramine, but the duration of effect is longer, for up to eight hours.
Diphenhydramine is usually used in higher strength than doxylamine.
Doxylamine is used with peroxide to treat nausea and vomiting during pregnancy on prescription.
Diphenhydramine is used for managing muscle movement in early Parkinson’s disease
Dosing Guidelines
The following outlines standard dosing requirements for using doxylamine and diphenhydramine:
Use: | Doxylamine: | Diphenhydramine: |
Cold and cough: | • Take every four to six hours as directed on the label | • Take every four to six hours as directed on the package label |
Insomnia: | • Take 30 minutes before bedtime as directed on the label | • Take 30 minutes before bedtime as directed on the label |
Vomiting and nausea in pregnancy: | • One tablet at bedtime on day one. If symptoms persist on day two, take one tablet in the morning and one at bedtime. | • N/A |
Motion sickness: | • N/A | • Take one to two tablets every four to six hours |
Parkinson's disease: | • N/A | • 10-50 mg IV or 100-400 mg intramuscularly |
Dosing in Children
Do not use doxylamine and diphenhydramine in children younger than 12 years old for insomnia.
Conversely, do not use these drugs for cough and cold in children younger than 4 years old.
And overall, regardless of use, when administering doxylamine or diphenhydramine to a child under 12 years old, first consult a healthcare provider.
Safe Use Guidance
The following provides suggestions to maximize the safety and efficacy of your prescription while taking doxylamine or diphenhydramine:
Do not take alcoholic beverages when taking doxylamine or diphenhydramine.
Do not take these medicines during the day if used for insomnia.
Doxylamine and diphenhydramine are short-term treatments for insomnia. Stop using it and call your healthcare provider if your symptoms do not improve within two weeks.
Talk to your healthcare provider if you are pregnant or plan to become pregnant or breastfeeding before taking doxylamine or diphenhydramine.
Be aware of some brands of chewable tablets and rapidly disintegrating diphenhydramine tablets containing aspartame. Do not use these brands if you have phenylketonuria (PKU is an inherited condition in which a special diet must be followed to prevent damage to the brain to prevent severe intellectual disability).
Doxylamine and diphenhydramine may cause drowsiness. Do not drive a car or operate machinery until you know how these drugs affect you.
Side Effects and Safety
Doxylamine and diphenhydramine are considered safe and effective when taken as their respective labels recommend.
However, like all drugs, doxylamine and diphenhydramine carry the potential for side effects.
Therefore, monitor yourself or a loved one closely for the emergence of side effects that worsen or fail to dissipate over time.
Common Side Effects
Common side effects associated with the use of doxylamine and diphenhydramine include:
Diphenhydramine-Specific Side Effects
Diphenhydramine, by itself, may cause the following side effects:
Dizziness
Loss of appetite
Vomiting
Constipation
Muscle weakness
Severe Side Effects
Some severe side effects of doxylamine and diphenhydramine include:
Use in Older Adults
OTC sleep medications containing diphenhydramine and doxylamine may increase the risk of liver and kidney dysfunction, drug interactions, worsened side effects events, hangover effects, dizziness, or falls, especially in older adults.
As such, talk to your healthcare provider before taking doxylamine or diphenhydramine if you're 65 years or older.
When to Avoid
Discuss with your healthcare provider before taking doxylamine and diphenhydramine if you have or have ever had the following conditions:
Difficulty urinating (due to an enlarged prostate gland)
Potential For Next-Day Drowsiness
Antihistamines, including doxylamine and diphenhydramine, may cause drowsiness.
When taking doxylamine or diphenhydramine for insomnia, plan to achieve a full night's rest (seven to eight hours) after dosing.
If you get up too soon after taking either medication, you may feel drowsiness or a hangover.
Alternative Treatment Options
Common alternative cold remedies include zinc supplements, garlic, vitamin C, honey, ginseng, and ginger.
Similarly, there are alternatives to medicines to improve sleep patterns in insomnia.
Non-pharmacological therapies include limiting daytime naps, avoiding late-night dinners, and evening intake of alcohol, caffeine, or smoking.
It also involves a healthy diet, exercise, regular sleep, and waking time schedules. Meditation or yoga can help to improve the sleeping pattern and reduce underlying anxiety and stress.
Another beneficial therapeutic option in the management of insomnia is cognitive behavioral therapy.
Summary
Doxylamine and diphenhydramine are antihistamine drugs primarily used to relieve symptoms of allergic rhinitis and as a short-term treatment for insomnia.
And while healthcare providers generally view them as similar, they share notable differences.
Doxylamine and diphenhydramine are available in various combination products for their FDA-approved uses.
However, doxylamine and diphenhydramine differ in their dosing potency. Diphenhydramine is usually available in higher doses for the same uses as doxylamine.
Both these drugs can cause drowsiness. It is essential to avoid alcohol when taking these drugs for insomnia.
Ensure how these drugs affect you before doing any activity that requires mental alertness, such as driving and operating machinery.
Frequently Asked Questions
How do I store orally administered doxylamine or diphenhydramine?
For either medication, store away from any location susceptible to high levels of heat or moisture (such as a bathroom) at room temperature (68-77 degrees F).
Additionally, if relevant, keep doxylamine or diphenhydramine out of reach of children and pets.
How long is doxylamine or diphenhydramine used to treat allergy symptoms?
Doxylamine and diphenhydramine may improve the symptoms within a week.
Call your healthcare provider if symptoms do not improve after seven days.
For the treatment of allergy or cold symptoms, how quickly will each drug work?
Doxylamine and diphenhydramine start working within 20-30 minutes after oral administration for cold or allergy symptoms.
Read the original article on Verywell Health.
