Benadryl vs Sudafed

Benadryl vs Sudafed
November 8, 2015 7:47 PM

This article compares Benadryl vs Sudafed for treatment of sleep disorders, motion sickness, cough, itchiness, nausea, etc. Medical applications, uses, pharmacokinetic properties, side effects and precautions of both drugs are compared.


Benadryl is the brand name used for many different medications. It contains antihistamine diphenhydramine in the United States and Canada. It contains either long acting antihistamine cetirizine or acrivastine in the United Kingdom. This medicine is sold as cough medicine in New Zealand and Australia and no antihistamine is present in it (1).

This drug is used either for topical or oral use. It is sold as over-the-counter by Johnson and Johnson subsidiary McNeil Consumer Healthcare. Benadryl was marketed by Pfizer Consumer Healthcare in 2007. About 100 mg of Guaifenesin and 30 mg of pseudoephedrine hydrochloride are present in 5 ml of Benadryl Chesty cough and Nasal Congestion.

The most popular medication which uses the brand name of Benadryl is diphenhydramine.

It is a first general antihistamine which has antiemetic, antitussive, anticholinergic and sedative properties and is commonly used to treat allergies. Drug induced Parkinsonism and extrapyramidal symptoms are also managed by this drug. This drug has a strong hypnotic effect and the FDA has approved this drug as a nonprescription sleep aid in the form of diphenhydramine citrate.

This drug is the first antihistamine made in the 1940s and is the prototype of first generation antihistamines which include phenyltoloxamine, dolxylamine, orphenadrine, and other halogenated diphenhydramine derivates.

This drug was first synthesized by George Rieveschi and was first made publicly available through prescription in 1946 (2).

Medical applications

Benadryl is a first generation antihistamine and is used to treat a variety of different health problems which include:

  • Itchiness
  • Common cold
  • Motion sickness
  • Extrapyramidal symptoms
  • Insomnia

This drug is especially beneficial for the treatment of certain allergies. This drug helps a person to relax and fall asleep. This drug blocks a natural substance known as histamine which is made by the body during an allergic reaction. This drug also has drying effects. It is also helpful against running nose and watery eyes.

There is a controversy over using this drug for the treatment of cough and cold. It is considered safe in adults but unsafe for children younger than 6 years. So you shouldn’t use this drug for the treatment of cold symptoms in children younger than 6. The age limit can be up to 12 years if there are tablets or capsules. You should consult your doctor to know how to use this drug safely.

Benadryl is used for the treatment of Parkinson’s disease-like extra pyramidal symptoms which are caused by antipsychotics. This drug can also cause strong sedation and has been used as an anxiolytic. A recent study has proven that this drug has mild anti obsessive effects against obsessive compulsive disorder (OCD). This drug is a control medication and produces a significant reduction in OCD symptoms.

This drug is widely used as a sleep aid against insomnia because of the sedative properties present in it. The maximum dosage for this drug as recommended by the FDA is 50 mg. This drug is an ingredient in many sleep drugs either alone or in the combination of other ingredients. Some products which contain this drug include Tylenol Simply Sleep, Unisom, Sominex, ZzQuil and Nytol.

The main problem with Benadryl is its toleration effect. This drug isn’t much effective after three days of consecutive use. It has been seen that the effects of this drug are no more than the placebo. A study was conducted in 2002 in which 15 subjects were divided into two groups (3). The first group was given 50 mg benadryl twice a day for days whereas the second group was given the placebo tablet for 4 days. It was seen that the subjects developed tolerance to Benadryl in four days.

Dosage and intake methods

About 25 mg of diphenhydramine are present in each tablet and liquid filled capsule of Benadryl. There are about 12.5 mg per teaspoon in children’s Benadryl.

You should never open the capsule in case you are using a Benadryl capsule. Swallow the whole tablet. You shouldn’t use a kitchen spoon for measuring if you are using Benadryl liquid. Use the measuring cup to measure the drug amount.

The common doses for Benadryl are mentioned below:

  • Children with age greater than 12 should use 1 to 2 capsules or tablets every 4 to 6 hours.
  • Children from age 6 to 11 should take only one tablet or capsule every 4 to 6 hours. They can also take one to teaspoon of Benadryl liquid every 4 to 6 hours.
  • You should consult a doctor if you have a child younger than 6 and you want him to take this drug.

Intake methods

Benadryl comes in many forms like a rapidly disintegrating tablet, a liquid filled capsule, a capsule, powder, dissolving strip and liquid taken by the mouth. This drug should be taken every 4 to 6 hours when used for the treatment of cold, cough and allergy symptoms. This drug should be taken 30 minutes before departure, if someone has motion sickness. It can also be taken after meals and before bed time. This drug should be taken about 30 minutes before sleep when used for insomnia. This drug should be taken up to 3 to 4 times a day to treat abnormal movements.

The following are the main intake methods of this medicine:

  • Dissolving strips: This drug comes in the form of dissolving strips. You should place the dissolving strip on your tongue and wait for it to melt. Swallow the tablet when it has melted down.
  • Liquid form: You shouldn’t use a household spoon to measure the liquid dosage. You should either use the cup which comes with the medication or use a spoon specially designed for measuring this drug.
  • Capsules: Don’t try to break the capsules. Just take the capsule with a glass of water and swallow it whole.
  • Rapidly dissolving tablets: You should take the tablet and place it in your tongue and close your mouth. The tablet is dissolved quickly with or without water.

Mechanism of benadryl

Benadryl is an inverse agonist of histamine H1 receptor (4). The class to which this drug belongs is the athanolamine class of antihistaminergic agents. The intensity of different allergic symptoms can be reduced when the effect of histamine on the capillaries is reversed. This drug can also cross the blood brain barrier and it antagonizes the H1 receptors centrally. The effect of the H1 receptors leads to drowsiness.

Benadryl is a potent antimuscarinic like other first generation antihistamines and the high doses of this drug can cause anticholinergic syndrome. Benadryl has antiparkinson properties in it and it has blocking properties on the muscarinic acetylcholine receptors in the brain.

This drug also functions as a sodium channel blocker and is responsible for its actions as an anesthetic. The reuptake of serotonin is also inhibited by Benadryl. This drug has shown to be a potentiator of analgesia which is caused by morphine but not by endogenous opioids in rats.


The pharmacokinetics of Benadryl can be divided into the following steps:

1. Absorption

This drug is well absorbed through oral administration and the drug appears in the plasma within 15 minutes. The systematic availability is affected by the high first-pass metabolism and only 40-60% of the dose reaches the systematic circulation in the form of unchanged Benadryl. The concentration level of plasma becomes highest within 1 to 4 hours. The sedative effect becomes maximum after 1-3 hours administration of a single dose and is positively correlated with the plasma drug concentration. Drowsiness is also caused and sleep occurs at the plasma concentrations of 70 ng/ml or greater than that.

2. Distribution

Benadryl is distributed throughout the body which also includes the central nervous system. The drug crosses placenta and it has been detected in the human milk to some extent. But the ratio isn’t clearly defined. Benadryl is about 80-85% protein in the vitro. There have been reports of less extensive protein binding in healthy adults and adults with cirrhosis.

3. Metabolism

Benadryl is widely and almost completely metabolized in the body. A single dose of Benadryl is about 100 mg. About 50-75% of it is excreted through the urine in 4 days as completely as metabolites. Major urinary excretion is caused during the first 24-28 hours. Only about 1% of the single dose goes through the urine unchanged.

4. Elimination

The terminal elimination of half-life of this drug is from 2.4 to 9.3 hours in healthy adults. It is may be more in adults suffering from liver cirrhosis.

Benadryl overdose

Benadryl overdose is quite a serious issue and should be handled with great care. Over dose occurs when a person either accidently or intentionally consume more than the recommended dosage for the drug.

The overdose of Benadryl comes under poison exposure. You should immediately call emergency number 911 or the National Poison Control Center at 1-800-222-1222 (5).

There are a number of symptoms of Benadryl overdose but the most common symptoms of the drug are shown below:

  • Difficulty urinating
  • Blurred vision
  • Low blood pressure
  • Rapid heart beat
  • Depression
  • Hallucinations
  • Drowsiness

Side effects

There are a number of side effects of Benadryl.

Serious side effects

Some serious side effects include blurred vision, stomach upset and dry eye. You should inform the doctor at once if any of these side effects occur to you persistently.

You should chew gums, suck hard candy, drink water or use a saliva substitute to get rid of dry mouth. You should remember one thing here and it is that if the doctor has directed this medicine for you it is because its health benefits are greater than its side effects.

Most of the people who use this medicine don’t suffer from any serious side effects.

You should also inform your doctor if you suffer from side effects like sudden mood changes, fast heartbeats and difficulty urinating. You should also get medical help if you suffer from seizures.

Sometimes allergic reactions are also caused due to the drug but it is quite rare. But you should get medical help if you suffer from any side effects of an allergic reaction like itching/swelling, rashes, dizziness and trouble breathing.

Rare side effects of Benadryl

Sometimes intestinal problems can occur which include nausea, vomiting or loss of appetite. These side effects usually occur in people who take the drug on a regular basis. Sometimes, constipation can also occur when taking heavy doses of this drug.

Fatigue due to this drug can become intense in some cases. Some patients have reported of irritability, shakiness and nervousness. Some have also reported to suffer from other discomforts which lead to unbalance.

You shouldn’t operate any kind of machinery if these side effects occur. Sometimes you may develop tolerance to the drug which will limit the side effects but it will take time.

You should talk to your doctor if you suffer serious side effects or if these side effects limit your ability to function normally. The doctor may pair this medication with an alternate drug to minimize the side effects.

This drug shouldn’t be given to infants and young children.

The reason is that the bodies of children aren’t capable of handling the reactions which take place in the body by the intake of this drug and many side effects may occur.

You should immediately call a poison helpline if your child accidently or intentionally ingests the drug.

Pregnant women should also avoid taking Benadryl and should take it only under the supervision of a doctor. Currently there are no studies which show that the fetus is damaged due to the use of Benadryl.

But the main thing is that Benadryl can interact with other medications taken during pregnancy and cause many problems.

Moderate side effects

Some moderate or less severe side effects of the intake of Benadryl are specified below:

  • Dry nose
  • Drowsiness
  • Nausea
  • Headache
  • Feeling jittery
  • Weakness
  • Dizziness
  • Ringing in ears
  • Stomach cramps
  • Throat dryness
  • Over excitement
  • Hives

You should inform your doctor if you suffer from any side effects or report the side effect to FDA at 1-800-FDA at 1-800-FDA-1088.

Decreased efficiency causes

The following things decrease the overall efficiency of Benadryl:

  • The overall efficiency of Benadryl is decreased when it interacts with other drugs. Some common drugs which can interact with Benadryl are Ambien, Clonazepam, Gabapentin, Tramadol, Trazodone, Zyrtec and Xanax.
  • Alcohol should never be taken when a person is taking Benadryl. The reason is that alcohol can interact with Benadryl and cause allergies.
  • Other people who should beware about the use of Benadryl are cardiovascular patients and liver disease patients. These patients should avoid taking Benadryl because the drugs prescribed to these patients may react with Benadryl and cause different kinds of problems.


Sudafed is a brand name and is registered under the trademark of over the counter decongestants. This drug is manufactured by McNeil Laboratories and is available for sale in Canada, Ireland, South Africa, New Zealand, United States and the United Kingdom. The previous owner of Sudafed before Johnson and Johnson, was Pfizer.

This drug is used for the treatment of different symptoms like nasal congestion, cold, sinusitis and allergies (6). Pseudoephedrine was present as an active ingredient in the original formulation of the drug. But formulations which don’t contain pseudoephedrine are also being sold under the brand name Sudafed.

Different formulations of Sudafed contain different active ingredients. Some of these active ingredients have been mentioned below:

  • Pseudoephedrine – it is the active ingredient of the original Sudafed. It is being sold under the brand name “Sudafed Decongestant” in the United States.
  • Xylometazoline – it is the active ingredient in the product formulated as nasal spray and is sold in United Kingdom under the name Sudafed Nasal Spray.
  • Oxymetazoline – this is the active ingredient present in the name Sudafed OM in the United States and is formulated as a nasal spray.
  • Paracetamol – it is sold under different brand names like Sudafed blocked nose and sinus capsules, Sudafed Day and Night capsules and Flu tablets.
  • Caffeine – it is sold under the names Sudafed blocked nose and Sinus capsule and Sudafed Day and Night capsules.
  • Ibuprofen – It is sold as Sudafed Sinus Pressure and Pain tablets.

Medical uses of Sudafed

There are a number of health benefits of Sudafed. This drug is used for the temporary relief of stuffy nose and the sinus infection caused by infection/allergies or other breathing illnesses like hay fever, bronchitis and allergies. This drug is a decongestant which means it narrows the blood vessels and reduces the swelling and congestion (7).

You should carefully read the manufacturer’s package instructions in case you are doing self-treatment. This is for knowing when to consult a doctor or pharmacist.

You should remember that this product should be kept away from the reach of children.

Cough and cold products are generally considered unsafe for children under the age of 6 years.

Capsules and tablets aren’t recommended for children younger than 12 years. You should consult your doctor about how to use the product safely.

This drug is suitable for use against cough. A study done in 2006 showed that this drug is effective for the suppression of cough (8). But the study wasn’t done on human subjects; the study was done on pigs.

This drug does not shorten the length of common cold and can lead to serious side effects. You should carefully follow the dosage instructions to minimize the side effects.

You should not use this drug to make a child sleep. Ask the doctor for other healthy alternatives for kids to relieve the cold and cough symptoms (7).

Sometimes doctors prescribe this medicine to reduce the swelling and pain in the ear or help to open the ear canal when there is change in air passage. You should follow the instructions of the doctor carefully.

Dosage and intake methods

There are different dosages of Sudafed for different age groups. The specific dosage according to each age group has been mentioned below:

  • 2 to 5 years children – the immediate dosage for this group of children is 15 mg every 6 hours. The appropriate dosage for sustained release suspension is 12.5 to 25 mg every 12 hours. The maximum dose shouldn’t exceed from 60 mg/day.
  • 6 to 12 years children – the immediate dosage for this group is 30 mg every 6 hours. The sustained release suspension dosage is 25 to 50 mg every 12 hours. The maximum dosage shouldn’t exceed from 120 mg/day.
  • Over 12 years – The immediate dosage for this group is 30 to 60 mg every 6 hours. The sustained release dosage is about 120 mg every 12 hours. The maximum daily dose is 240 mg/day.

Intake methods

You should read the instructions on the label carefully if you want to do self-treatment. You should always consult a doctor or pharmacist if you have any confusion.

You should take this medicine this medicine with or without food after every 4 to 6 hours. Don’t ingest more than 4 doses on daily basis.

The appropriate dosage is based on your treatment, age and response to the treatment. Don’t go on increasing the dosage all by yourself or take more than the recommended dosage.

The following are the different intake methods of this drug:

  • Chewable tablets – You should chew each tablet well and swallow it if you are taking this medicine in the form of chewable tablets. There are many different brands of tablets available in the market. Some tablets need to be swallowed with plenty of water whereas others require no water. You shouldn’t break or crush the chewable tablets; swallow them whole. You should read the package carefully and read the dosage instructions for each product. Don’t take this drug more than written on the package.
  • Liquid form – Sudafed is also available as a syrup in the market. Don’t use a household spoon to measure the dose if you are taking it in liquid form. You should always use the measuring spoon or the cup which comes with the medication.


The following precautions should be observed with respect to Sudafed:

  • Don’t take the medication if you are taking a prescription of monoamine oxidase inhibitor (MAOI) or within two weeks of taking MAOI drug. You should ask a doctor or a pharmacist if your prescription doesn’t contain monoamine oxidase inhibitor.
  • You should ask a doctor before the use of this drug if you have high blood pressure, thyroid disease, heart disease, diabetes or have trouble urinating due to enlargement of prostate gland. You should always use the recommended dosage when using this product.
  • Stop using the medicine and ask the doctor if you feel nervousness, sleeplessness or dizziness. You should also ask the doctor if the symptoms of the disease don’t improve within 7 days or occur with a fever.
  • Pregnant and breastfeeding women should consult a doctor before taking this drug.

Mechanism of action

Sudafed is a sympathomimetic amine. The main action of the drug on the body depends on its reaction on the adrenergic receptor system. The vasoconstriction caused by the drug is principally an alpha-adrenergic receptor response (9).

This drug acts on the alpha and beta2-adrenergic receptor which causes vasoconstriction and relaxation of the smooth muscle in the bronchi respectively. These alpha-adrenergic are present on the muscle lining of the walls of blood vessels.

The muscles contract when the receptors are activated which causes the constriction of the blood vessel. Less fluid leaves the blood vessels due to constricted blood vessels and enters the nose and sinus linings which causes inflammation and decreased mucus production.

The beta2-adrenergic receptor leads to relaxation of the smooth muscles in the bronchi which causes bronchial dilation which decreases congestion and causes difficulty in breathing.


The following steps are involved after the intake of the drug:

1. Absorption

Sudafed is absorbed in the body through the gut after the oral administration. The Cmax of Sudafed was 180 ng/ml after the administration of one 60 mg Sudafed tablet to healthy adult volunteers. The tmax reached between 1.5 to 2 hours.

2. Distribution

The volume of distribution of Sudafed is about 2.8 I/kg.

3. Metabolism and elimination

The half-life of the drug is about 5.5 hours. The drug is metabolized in the liver by N-demethylation to nor-pseudoephedrine which is an active metabolite. Sudafed and its different metabolites are excreted form the body through urination. About 55% to 90% is excreted unchanged. The rate of the elimination increases when the urine is acidified. The rate of urinary elimination slows down when the pH of urine falls.


Overdose of Sudafed may lead to cardiovascular and neurological anomalies which include change in breathing, convulsions, increase in heart rate and hallucinations (10).

You should immediately get help if you think you have overdosed on the drug.

You should get help from a poison control center or a nearby emergency hospital room.

You should call 911 when someone has collapsed or isn’t breathing.

Side effects of Sudafed

Sudafed can cause a number of side effects. These side effects can be divided into two categories which have been mentioned below:

Severe side effects

Some potentially dangerous side effects of Sudafed are shown below:

  • Excitability
  • Nervousness
  • Stomach pain
  • Insomnia
  • Changes in heart rate and activity
  • Difficulty in breathing
  • Anxiety
  • Fear
  • Tenseness
  • Hallucinations
  • Tremors
  • Seizures
  • Painful urination
  • Cardiovascular collapse

Common side effects

Some common side effects of Sudafed are described below:

  • Nausea
  • Vomiting
  • Weakness
  • Headache
  • Restlessness

Decreased efficiency causes

The following things reduce the efficiency of Sudafed:

  • Sudafed can interact with a number of medications; this can decrease the overall efficiency of Sudafed. Some common medications which can interact with Sudafed include Allegra, Ambien, Benadryl, Flonase, Lyrica, vitamin D2, vitamin D3, Zyrtec and Xanax.
  • Certain beverages like energy drinks, sodas, teas and coffee can increase restlessness and insomnia in sensitive individuals. So you should avoid drinking these beverages. You should consult a doctor if you want to drink these beverages while taking the medication.

Clinical trials comparing Benadryl vs Sudafed

There isn’t any exclusive study which gives a comparison between Benadryl and Sudafed.

The following studies have been done relating Benadryl and Sudafed:

  • A study was done in 2005 to find the effectiveness of Benadryl for treating insomnia. About 184 patients were included in the study who were suffering from mild insomnia. The researchers in the study divided the patients into two groups, one group was given Benadryl as a sleep drug whereas the other group was given a placebo drug. The results of the study showed a significant effectiveness of the use of Benadryl compared to that of placebo.
  • There is a general perception that Sudafed makes a person sleepy. But currently there aren’t any studies to prove its effectiveness.
  • A study was done to find the effectiveness of Benadryl against nasal congestion, nausea and vomiting. Different methods were used in the study like double blind method, parallel assignment etc. The design of the study was such that the patients were given different doses of the drug at different periods of time. A total of 180 patients were involved in the study. The study showed that Benadryl is quite effective as a standard therapy for treating nasal congestion, nausea and vomiting.
  • A study was done in 2003 regarding the effectiveness of Sudafed for nasal congestion. The study proved that Sudafed is somewhat effective in treating nasal congestion but the study showed that large doses of Sudafed have the same effect against nasal as small doses of other drugs. The study showed that a dose of about 240 mg of Sudafed will have the same effect as that of 10 mg of montelukast sodium.


The comparison of the two drugs seems to show that Benadryl is the better drug out of the two. There are two reasons for this. The first reason is that there are studies which have shown the effectiveness of Benadryl against sleep disorders but there is no study showing the effectiveness of Sudafed against insomnia. The second reason is that a small dose of Benadryl will have the same effect as a large dose of Sudafed against nasal congestion. These things make Benadryl a better drug out of the two. So, you should choose Benadryl if you want to address your sleep issues or nasal issues.

However keep in mind that only your physician is responsible for proper treatment of any disease and if you do not feel well you should always go to see your doctor and ask him or her for proper medication. Never self treat yourself using information found on the web. Always ask your physician for advice!

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Written by: Michal Vilímovský (EN)
Education: Medical student, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
Article resources: See numbered references within the post.
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Published: November 8, 2015 7:47 PM
Next scheduled update: November 8, 2017 7:47 PM
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