How often can you take Excedrin Migraine?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Jan 31, 2023.

The usual adult dose for Excedrin Migraine is 2 caplets with a glass of water. Do not take more than 2 caplets in a 24 hour period, unless directed by your doctor.

Excedrin Migraine contains 250 mg of acetaminophen, 250 mg of aspirin (an NSAID), and 65 mg of caffeine per caplet or geltab. Taking more than 2 caplets in 24 hours may cause an overdose of acetaminophen, especially if you are using other medicines that contain acetaminophen. Taking too much acetaminophen may damage your liver or cause death. In case of an overdose, get medical help right away or contact a poison control center at 1-800-222-1222.

Before you use Excedrin Migraine, you should review the full Drug Facts label product information on the bottle. If your migraine headache symptoms persist or worsen, contact your doctor.

Excedrin Migraine is not for use in children. For patients under 18 years of age, ask your doctor. Do not give Excedrin Migraine to a child or teenager with a fever, flu symptoms, or chicken pox. Aspirin can cause Reye’s syndrome, a serious and sometimes fatal condition in children.

If you are pregnant or breastfeeding, ask your doctor before using Excedrin Migraine.

Why does Excedrin Migraine contain caffeine?

Excedrin Migraine is an analgesic combination over-the-counter (OTC) medication used to treat migraine headaches. It contains 250 mg of acetaminophen, 250 mg of aspirin (an NSAID), and 65 mg of caffeine per caplet or geltab. In this product, aspirin and acetaminophen are headache pain relievers and caffeine helps to enhance the pain-relieving effect of these 2 medicines.

Excedrin Migraine does not require a prescription.

Why was Excedrin Migraine recalled?

In October 2020, certain products and lots of Excedrin products were recalled by GSK Consumer Healthcare due to the possibility of holes in the bottom of bottles supplied by a bottle manufacturer. No Excedrin products were permanently discontinued, including Excedrin Migraine.

The Excedrin products that were impacted in the recall included specific lots and bottle sizes of:

• Excedrin Migraine Caplets or Geltabs
• Excedrin Extra Strength Caplets
• Excedrin PM Headache Caplets
• Excedrin Tension Headache Caplets

Bottle sizes included in the recall were the 50, 80, 100, 125, 200, 250 and 300-count bottles.

Products NOT impacted in the recall include the 24-count bottles of Excedrin Extra Strength caplets and the 24-count bottles of Excedrin Migraine caplets and geltabs. Excedrin Migraine is typically available in pharmacies, grocery stores and other retail outlets in the U.S.

GSK Consumer Health recommends that consumers should immediately inspect their Excedrin bottle for holes.

• If a hole is found, consumers should discontinue use but retain the bottle and contact GSK. GSK will retrieve the product and issue a refund.
• If no hole is found, consumers may continue to use the drug as directed.
• You can contact GSK Consumer Healthcare at 1-800-468-7746 (M-F, 8AM – 6PM) for more information.

Related: Comparing Excedrin vs Excedrin Migraine

This is not all the information you need to know about Excedrin Migraine for safe and effective use. Review the full Excedrin Migraine information here, and discuss this information and any questions you have with your doctor or other health care provider.

References

• Excedrin Products: Ingredients and Dosage. GSK Consumer Healthcare. Accessed Feb. 10, 2021 at https://www.excedrin.com/dosage-ingredients-chart/
• Excedrin Migraine (acetaminophen, aspirin, and caffeine) monograph. Drugs.com. Accessed Feb. 10, 2021 at https://www.drugs.com/excedrin-migraine.html
• Temporarily out of stock or recalled Excedrin products. GSK Consumer Healthcare. Accessed Feb. 10, 2021 at https://www. excedrin.com/products/discontinued/

Related medical questions

• Can you take ibuprofen with Excedrin Migraine?
• Can you take Excedrin Migraine while pregnant?
• How long does it take for Excedrin Migraine to work?
• How much caffeine is in Excedrin Migraine?
• Does caffeine help migraines?
• What are the side effects of beta blockers?
• What are the side effects of the flu vaccine?
• Why does throwing up relieve migraines?
• Do daith or tragus piercings help with migraines?
• Can depression cause headaches?
• What causes optical migraines?

Drug information

• Excedrin Migraine

Related support groups

• Excedrin Migraine
  (15 questions, 17 members)
• Headache Relief
  (1 questions, 10 members)
• Migraine
  (266 questions, 1,609 members)

Medical Disclaimer

Excedrin Ingredients and Dosage Information

Learn more about the pain-fighting ingredients in Excedrin® pain relief products, as well as Head Care* ingredients and suggested use.

INGREDIENTS & DOSAGE GUIDELINES

Select one to see the ingredients and dosage guidelines. All Excedrin products should be taken with a full glass of water.

• Excedrin Headache & Migraine Relief: Ingredients & Dosage Guidelines

  Aspirin

  Acetaminophen

  Caffeine

  Has been a go-to for all types of pain for decades, including headache and migraines.

  Is a powerful ingredient for pain relief, and is tough when fighting headaches.

  Enhances pain-relieving function of aspirin and acetaminophen.

  Use only as directed. Read all warnings and product information prior to use. Always follow label directions

• Head Care Proactive Health Ingredients & Supplement Facts*

  Magnesium

  Riboflavin

  Vitamin B6, Folic Acid, Vitamin B12

  Essential nutrient that helps support blood flow in the brain for head comfort.

  Read all warnings and product information prior to use. Always follow label directions.

HOW THE ACTIVE INGREDIENTS IN EXCEDRIN HEADACHE & MIGRAINE RELIEF WORK TOGETHER TO STOP HEADACHES

Evidence suggests that the use of combination analgesics such as Excedrin offer advantages in the treatment of headaches by targeting pain in more than one way.^[3]

Excedrin’s specialized formula contains two pain relievers (acetaminophen and aspirin) plus an amplifier (caffeine) that work together to target head pain.   Aspirin is a non-steroidal anti-inflammatory drug or NSAID.  Aspirin helps to block the production of pain signaling chemicals called prostaglandins.  The way in which acetaminophen works is still not well understood.  However, it is believed to elevate the pain threshold. This allows you to tolerate more pain, therefore providing pain relief. Finally, caffeine has been shown to increase the potency of aspirin and acetaminophen by up to 40 percent. This means less acetaminophen and aspirin is needed to relieve your migraine pain when combined with caffeine^.[3,4,5]

Acetaminophen, aspirin and caffeine, when taken as directed, provide clinically proven headache relief. Excedrin is a combination of these ingredients: two pain relievers, plus an amplifier to enhance the analgesic effect.

Acetaminophen, also known as paracetamol, should not be taken with other medicines that also contain acetaminophen.  Acetaminophen is contained in many medicines to treat pain, fever, symptoms of cold and flu, and sleep medicines.  Do not take more than recommended dose, as this may be harmful, including serious harm to your liver.  If you have liver or kidney disease, talk to your doctor before taking acetaminophen.​

EXTRA STRENGTH

MIGRAINE

TENSION HEADACHE

PM HEADACHE

Contains Acetaminophen

(250 mg per tablet)

(250 mg per tablet)

(500 mg per tablet)

(250 mg per tablet)

Contains Aspirin

(250 mg per tablet)

(250 mg per tablet)

(250 mg per tablet)

Contains Caffeine

(65 mg per tablet)

(65 mg per tablet)

(65 mg per tablet)

Contains Diphenhydramine (Sleep Aid)

(38 mg per tablet)

12 Years & Older

18 Years & Older

12 Years & Older

12 Years & Older

2 Every 6 Hours

(Max.

Contains Electrolytes

Contains Caffeine

Contains Melatonin

18 Years or Older

18 Years or Older

18 Years or Older

Frequency

1 tablet per day

Limit 2 packets per day

Limit 1 packet per day

Available in Tablets

Available as a Powder

CAFFEINE: A KEY INGREDIENT TO THE EXCEDRIN LIST

You may have heard that caffeine can cause or exacerbate headaches, and if so, you’re probably wondering why there’s caffeine in most Excedrin pain relief products.

It’s true that caffeine can be a headache trigger in certain situations, but that’s far from the full story.

Caffeine is referred to as an ‘analgesic adjuvant’. This means that it helps to boost the effects of certain pain relievers. In the case of Excedrin pain relief products, caffeine boosts the pain-relieving effects of aspirin and acetaminophen – making these medicines up to 40% more effective.

That’s why you’ll find caffeine in almost all Excedrin pain relief products. As compared to falling asleep without melatonin. Melatonin helps you fall asleep and is for occasional sleepiness.* ^†Magnesium helps support proper blood flow to the brain.*

FIND THE EXCEDRIN PRODUCT THAT’S RIGHT FOR YOU

Excedrin has been a leader in headache relief for more than 50 years, and the range of Excedrin products contains something for every kind of headache, including tension headaches, nighttime headaches and migraines.

Discover the full Excedrin product range here, or, if you need more help finding the right product for you, try our interactive product selector.

Sources:

1. American Migraine Foundation. Understanding Caffeine Headaches. https://americanmigrainefoundation.org/resource-library/understanding-caffeine-headaches/. Accessed November 27, 2019. Referenced text is highlighted in source PDF.
2. Caffeine in the management of patients with headache. NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655397/. Accessed 10/12/19.WebMD. The Link Between Caffeine and Headac
3. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?. Straube et al. BMC Neurologly. https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-11-43. Accessed 20/03/20
4. How Do Pain Relievers Work? Johns Hopkins Medicine. https://www.hopkinsallchildrens.org/Patients-Families/Health-Library/HealthDocNew/How-Do-Pain-Relievers-Work. Accessed 31/03/20.
5. Aspirin and Migraine. National Headache Foundation. https://headaches.org/2007/10/25/aspirin-and-migraine/. Accessed 31/03/20.

EXCEDRIN^® MEANS FAST

Trusted products tough enough for different types of headaches.

SEE ALL PRODUCTS

$1 OFF EXCEDRIN

GET COUPONS

GET ANSWERS TO YOUR FREQUENTLY ASKED QUESTIONS

Excedrin® is a leading expert in headache education.

Excedrin Migraine vs Extra Strength: Difference & Comparison

Migraine is a medical condition in which the sufferer has a headache that usually affects one side of the head and causes extreme pain or worsening pain.

Health Quiz

Test your knowledge on health-related topics

1 / 10

What is the role of vitamin C in the body?

Supports healthy skin

Helps with iron absorption

Supports immune function

All of the above

2 / 10

What is the main cause of male infertility?

Poor diet

smoking

Lack of physical activity

Low sperm count

3 / 10

Which type of arthritis is most common?

Rheumatoid arthritis

osteoarthritis

Psoriatic arthritis

gout

4 / 10

What is the main cause of type 2 diabetes?

Heredity

Poor nutrition

Lack of physical activity

Stress

5 / 10

Which of the following diseases is caused by dog ​​bites?

Scurvy

insanity

Rabies

Colorblindness

6 / 10

What is the best way to improve mental health?

MEDITATION

Talk to someone about your feelings

Physical activity

Spending time alone

7 / 10

Which of the following is NOT a symptom of a cold?

Sore throat

Runny nose

Upset stomach

Cough

8 / 10

What is the recommended daily dose of vitamin D for an adult?

400 IU

600 IU

800 IU

1000 IU

9 / 10

What is the leading cause of death worldwide?

cancer

Heart disease

Stroke

Traffic accidents

10 / 10

What is the best way to prevent the spread of germs?

Coughing into your hand

Coughing into your sleeve

Frequent use of hand sanitizer

Do not cover your mouth when coughing

your bill

This is usually associated with nausea, diarrhea and excessive visual and hearing new reactivity. Migraine flares can last from minutes to weeks, and the suffering can be severe enough to prevent someone from doing their daily activities.

To get relief from this, Excedrin Migraine and Extra Strength are on the market,

Key Findings

1. Excedrin Migraine is designed specifically for migraine while Excedrin Extra Strength is designed to relieve various types of pain.
2. Both drugs contain acetaminophen, aspirin, and caffeine, but Excedrin Migraine has a different FDA-approved dosage for migraine relief.
3. Users may take higher doses of Excedrin Extra Strength for general pain relief, but must follow the recommended dosage of Excedrin Migraine to avoid possible side effects.

The difference between Excedrin Migraine and Extra Strength is that Excedrin Migraine contains ingredients in the formula that are not in Extra Strength. Three ingredients: caffeine, acetaminophen, and aspirin. Three ingredients work great for migraines and thus, this makes Excedrin Migraine different from Extra Strength.

Excedrin Migraine is said to be very effective. A survey report of various patients with migraine showed that Excedrin Migraine can eliminate 100% of the effect of migraine after a dose.

With that said, Excedrin is reported to have the side effects of a slight increase in heart rate.

The dosage of Extra Strength is a bit light. Up to 4 tablets can be consumed in one day. But such a dose can make a person weak or even cause nausea.

Although Extra Strength contains several ingredients, it does not contain the 3 main ingredients that have good anti-migraine properties.

Three ingredients: caffeine, acetaminophen, and aspirin. Extra Strength is best for mild migraines.

901 77

Comparison parameters	Excedrin Migraine	Extra Strength
Date of entry into the market.	It was released to the market in 1998.	It was released to the market in 1960.
dosage	Maximum intake of this 2 times a day.	Maximum intake of this 4 times a day.
Ingredients:	Caffeine is present in the formula along with acetaminophen, aspirin.	Free from acetaminophen, aspirin and caffeine.
Migraine types	It is best for severe headaches as it is more powerful.	It is suitable for mild headaches.
Side effect	Excedrin has reported a slight increase in heart rate in some patients.	No side effects of increased heart rate reported.

What is Excedrin for migraine?

Excedrin Migraine was released to the market in 1998 after Excedrin received approval from the Food and Drug Administration to release it as a commercial product.

Excedrin Migraine is said to be very effective. A survey report of various patients with migraine showed that Excedrin Migraine can eliminate 100% of the effect of migraine after a dose.

Excedrin has been reported to have side effects of a slight increase in heart rate, but with time and low drug intake, some other additional side effects appear, such as kidney and liver damage.

Excedrin Migraine is made up of three different ingredients that work very well for migraines. The three ingredients are acetaminophen, aspirin, and caffeine.

Caffeine has a long history as a migraine remedy, so the caffeine in Excedrin Migraine enhances the effectiveness of the product.

However, very few users may also report stomach problems after using Excedrin Migraine. The dosage of Excedrin is such that only 2 of them can be consumed in one day.

If you continue taking the drug for more than a week, you may experience signs of side effects.

Extra Strength is the first launch of Excedrin. It was launched on the market in 1960. It is one of the oldest on the market.

Extra Strength was one of the oldest products with multiple ingredients. Extra Strength can cure over 50% of migraine pain, but cannot eliminate 100% of the pain.

The dosage of Extra Strength is a bit light. Up to 4 tablets can be consumed in one day. But such a dose can make a person weak or even cause nausea.

Although Extra Strength contains several ingredients, it does not contain the 3 main ingredients that have good anti-migraine properties.

Three ingredients – caffeine, acetaminophen and aspirin. Extra Strength is best for mild migraine pain. There have been no reports of immediate side effects from Extra Strength such as increased heart rate.

The only possible explanation for the high dose limit would be that people with long-term headaches would actually take medication at any time and at any dose, minimizing the effect of the medication.

Main differences between Excedrin Migraine and Extra Strength

1. Excedrin Migraine was launched on the market in 1998 and Extra Strength was launched on the market in 1960.
2. The maximum intake of Excedrin Migraine is 2 times a day, while the maximum intake of Extra Strength is 4 times a day.
3. Excedrin has reported an increase in heart rate in some patients, while side effects of increased heart rate for Extra Strength have not been reported.
4. Excedrin Migraine is best for severe headaches because it is more powerful, while Extra Strength is good for mild headaches.
5. Caffeine is present in the Excedrin Migraine formula along with acetaminophen and aspirin, while acetaminophen, aspirin and caffeine are not present in the Extra Strength formula.

Recommendations

1. https://www.theneighborhoodacademy.org/editoruploads/files/Kamiya_Coles_-_Caffeine_in_Headache_Medicine.pdf
2. https://www.uspharmacist.com/article/ migraine-its-recognition-and- treatment?utm_source=TrendMD&utm_medium=cpc&utm_campaign=US_Pharmacist_TrendMD_1

Single request?

I put so much effort into writing this blog post to provide you with value. It will be very helpful for me if you consider sharing it on social networks or with your friends/family. SHARE ♥️

Sandeep Bhandari

Sandeep Bhandari holds a BS in Computer Science from Thapar University (2006). He has 20 years of experience in technology. He has a keen interest in various technical fields, including database systems, computer networks and programming. You can read more about him on his bio page.

Treatment of migraine attack: with or without prescription | #06/15

Migraine is a widespread neurological disease with a complex pathophysiological mechanism that manifests itself as recurrent attacks of throbbing unilateral headache that can be severe and accompanied by associated symptoms such as nausea, photophobia and phonophobia. In a third of patients, the development of headache is preceded by transient neurological symptoms, which are most often visual, but may also affect other senses, as well as speech (migraine with aura [1]). Migraine is extremely common and is a very “expensive” disease. Thus, in the European population, it occurs in 17% of women and 8% of men [2], while the cost of migraine in Europe reaches 18 billion dollars a year [3]. At the same time, according to the World Health Organization (WHO), migraine is one of the twenty diseases that most often lead to disability [4].

For decades, the majority of headache patients have used over-the-counter analgesics, including acetaminophen (paracetamol), acetylsalicylic acid, other non-steroidal anti-inflammatory drugs (NSAIDs), and fixed combinations such as acetylsalicylic acid (ASA) + acetaminophen (AAF) + caffeine (K) [5]. It is known that more than 90% of patients who used over-the-counter combination drugs used them specifically for the treatment of headache [6]. In all the years that prescription and over-the-counter drugs have been used to treat migraines, there have been no studies that directly compare the two drug categories. Perhaps this was due to the fact that prescription drugs are a priori considered to be more effective [7]. Recently, however, more and more data have appeared, both confirming the effectiveness of over-the-counter drugs in the treatment of migraine attacks, and substantiating their use in terms of the pathogenesis of the disease.

The role of inflammation in the pathogenesis of migraine headache

It is believed that the development of migraine headache is associated with activation and sensitization (decrease in the excitability threshold) of the trigeminocervical system [8–11]. Due to the fact that its participation allows to justify the appointment of a number of drugs used in the treatment of an attack, it seems interesting to make a small digression and dwell on it in a little more detail.

According to modern concepts, the development of migraine headache is associated with the activation and sensitization of afferent sensory fibers of the trigeminal nerve that innervate head tissues, including the meninges and their large blood vessels [9-eleven]. To date, there is no clear idea of ​​what exactly is the source of nociceptive impulses. These can be soft or hard membranes of the brain, as well as periarterial sensory fibers. It cannot be ruled out that each of these components contributes to the formation of the pain syndrome [10].

Based on a large amount of indirect evidence obtained both in preclinical and clinical studies, sterile inflammation of the meninges is considered as a key mechanism that may underlie the long-term activation and sensitization of perivascular meningeal afferent fibers during a migraine attack [10, 12, 13]. Such indirect data are an increase in the concentration of inflammatory mediators in the venous blood of the cranial veins during a migraine attack, as well as the effectiveness of non-steroidal anti-inflammatory drugs in the treatment of migraine attacks in most patients [12, 13]. In animal studies, activation of meningeal nociceptors in vivo leads to the release of vasoactive pro-inflammatory peptides such as calcitonin-binding peptide (CGBP) and substance P from peripheral nerve endings. These peptides induce vasodilation of meningeal blood vessels (predominantly due to CGSP), outflow of plasma from vessels, and local activation of dural mast cells (DMCs) with subsequent release of cytokines and other inflammatory mediators. In fact, we are talking about the development of neurogenic inflammation in the DM [11–13]. Degranulation of DM mast cells can lead to prolonged activation and sensitization of DM nociceptors (data obtained on rats), as well as cephalic tactile hypersensitivity [14]. Chemical inflammation of the dura mater in awake animals leads to the development of cutaneous allodynia in the facial area and in the area of ​​the hind legs [15], while the chronology of the development of these symptoms is similar to that in patients with migraine [16]. In addition, the pharmacology of allodynia induced by an “inflammatory cocktail” (an acidic mixture of potassium, prostaglandins, serotonin, bradykinin, and histamine that stimulates and sensitizes pain receptors, causing hyperalgesia) in animals allows for parallels with the clinical pharmacology of migraine pain [15] . The introduction of glycerol trinitrate, which can provoke a delayed migraine attack in patients (but not in healthy people!) that is almost indistinguishable from a spontaneous attack, causes the development of delayed inflammation in the dura mater of the rat [17].

However, the endogenous processes that cause the development of meningeal inflammation and peripheral sensitization during a spontaneous migraine attack remain unclear. Many researchers believe that neurogenic inflammation is the very endogenous inflammatory process that maintains the activation and causes sensitization of meningeal nociceptors during a migraine attack. The hypothesis of neurogenic inflammation is also supported by the fact that headache-inducing substances, such as ethanol and umbellulone (a volatile substance found in California laurel), activate peptidergic meningeal trigeminal afferent fibers (using various receptors: TRPV1 and TRPA1), which leads to the release of CGSP and the development of a neurogenic inflammatory response in the dura mater of experimental animals [18, 19].

An interesting fact: it is known that in a significant number of patients with migraine, an increase in headache occurs under the influence of light (photophobia). Relatively recently, the neuronal mechanism of this phenomenon was studied [20]. Neurons of the posterior thalamus innervating the DM receive monosynaptic projections from retinal ganglion cells (mainly internal photosensitive cells not involved in imaging), while light increases the activity of neurons innervating the DM. The hypothesis that a non-imaging pathway from the retina is involved in the development of photophobia is also supported by the fact that headache aggravation by light persists in blinded migraine patients who perceive light despite severe degeneration of rod photoreceptors and cones [20].

Thus, the modern theory of the development of a migraine attack suggests that the effectiveness of NSAIDs in such patients is associated with their effect on one of the key links in the pathogenetic process leading to the development of headache, namely, a sterile inflammatory process in the meninges of the brain.

“OTC” seizure therapy

Currently, a large number of large randomized placebo-controlled trials have been published on the treatment of migraine attacks. In most of these studies, the following criteria were used as criteria for successful treatment of a migraine attack [21]:

1) relief of pain after 2 hours;
2) decrease in intensity of headache from severe or moderate to mild or no headache after 2 hours;
3) the effectiveness of therapy is maintained in two cases out of three;
4) no headache recurrence and no need to take the drug within 24 hours of successful treatment.

Analgesics

Analgesics are the drugs of first choice for the treatment of mild to moderate migraine. Efficacy in the treatment of migraine has been confirmed in at least one placebo-controlled study for the following drugs: acetylsalicylic acid up to 1000 mg, ibuprofen 200-800 mg, diclofenac 50-100 mg, phenazone 100 mg, metamizole 1000 mg, tolfenamic acid 200 mg and paracetamol 1000 mg. Selective cyclooxygenase-2 (COX-2) inhibitors have also been studied in patients with migraine and have been shown to be effective. Analgesics with proven efficacy are presented in Table. 1. In order to avoid the development of abuse headache, simple analgesics should not be taken more than 15 days per month, and combined analgesics should not be taken more than 10 days per month [22].

What is a “recommendation level”? How is it evaluated? What does “A” mean? The concept itself came to us from evidence-based medicine and is derived from the level of evidence, which, in turn, is nothing more than a hierarchy of probably the best evidence indicating the effectiveness and safety of a particular drug (treatment method, medical device, etc.). . P.). Its meaning is to make it as easy as possible for the doctor (researcher, patient) to find the probably best evidence of the effectiveness of the ongoing or planned therapy. At the same time, you need to be aware that levels of evidence are in no way a substitute for systematic reviews, do not judge the quality of the available evidence, are not recommendations, and do not say anything about whether you phrase the question correctly. For example, if a patient is diagnosed with influenza instead of meningitis, finding the best cure for influenza is unlikely to produce clinical results.

In table. 2 presents the levels of evidence for assessing the effectiveness of therapy, prevention, etiology, harm to health.

The relationship between levels of evidence and levels of recommendations is shown in Table. 3.

Combined preparations

In 1993, the US Food and Drug Administration (FDA) recommended that caffeine (when added to an ASA + AAF combination) be classified as a Category 1 analgesic adjuvant, with “recognized efficacy and safety”. » [23]. The presence of caffeine makes it possible to shift the dose/response curve to the left, increasing the analgesic effect by 40% [23, 24]. The synergistic action of ASA, AAF and caffeine, leading to the suppression of prostaglandin E2 synthesis, may partially explain this phenomenon. Caffeine itself may have analgesic effects in certain types of human pain [25], but overall evidence from clinical trials is lacking.

In 1998, a combination of 250mg ASA, 250mg AAF, and 65mg caffeine became the first over-the-counter drug to receive FDA approval for the treatment of migraine, and later, in 1999, it was approved for the treatment of more than just migraine but also accompanying symptoms [7]. A similar combination has been approved in Europe and recommended by the European Federation of Neurological Societies (EFNS) as a first-line treatment for mild to moderate migraine (Table 1).

Data obtained in clinical studies indicate the safety and efficacy of fixed combinations of analgesics with the following dosages of active ingredients: ASA 250-265 mg, AAF 200-265 mg and caffeine 50-65 mg in one tablet. The optimal ratio of active ingredients of 1.0:0.8:0.2 (ASA, AAF and caffeine, respectively) was found in the course of pharmacological and clinical studies to find the optimal dose [23], while the minimum recommended dose of caffeine is 50 mg per tablet. . In patients with migraine with or without aura, the fixed combination is more effective than placebo not only in reducing the intensity of headache, but also in reducing the severity of nausea, photo- and phonophobia [26].

A comparative study of the fixed combination (ASA 250 mg + AAF 250 mg + caffeine 65 mg) and ibuprofen in the treatment of migraine showed that the effectiveness of both drugs exceeded that in the placebo group, while the triple combination was significantly more effective than ibuprofen [7]. The superiority of the fixed combination over ibuprofen was confirmed both statistically and clinically (reduction in pain intensity, earlier onset of a significant reduction in pain, as well as the frequency of patients with complete absence of pain and a headache response to the drug), where the most significant for patient performance indicators [27, 28]. In addition, in the fixed combination group, emergency drugs were used significantly less frequently, and the percentage of patients with complete relief of headache was higher than in the ibuprofen group [7].

Against the background of the prevailing opinion that prescription drugs are always the most effective, the data obtained in a comparative study of a fixed combination (ASA 250 mg + AAF 250 mg + caffeine 65 mg) with sumatriptan at a dose of 50 mg are interesting. Here, the effectiveness of the combination turned out to be higher in terms of the overall effectiveness of headache, relief of concomitant symptoms, the frequency of use of emergency drugs, and the overall assessment of the effectiveness of the drug [7].

In addition to the advantages associated with the effectiveness of the drug, the fixed combination has a number of other advantages compared to sumatriptan, in particular, it does not have cardiovascular contraindications that limit the use of triptans [29, 30].

The results of the study suggest that patients with migraine can use the triple combination at the first sign of an impending attack, while prescription drugs can be deferred for cases of refractory to OTC therapy, since most patients try OTC drugs before visiting the doctor. The assumption that prescription drugs are, by definition, superior to over-the-counter drugs can be challenged.

Conclusion

Thus, the data available to date confirm that over-the-counter drugs, in particular NSAIDs and their combinations, can be considered as effective pathogenetic agents for the treatment of mild to moderate migraine. That is how they are recommended by the European Federation of Neurological Societies and the US Headache Consortium.

Special mention deserves a fixed combination of ASA, AAF and caffeine in doses of 250, 250 and 65 mg, respectively. In Russia, this combination is available under the name Excedrin®. The advantages of the drug include compliance with the composition of European and American recommendations, effectiveness against both headache and concomitant symptoms of migraine (nausea, photo- and phonophobia) [26], as well as a favorable tolerability profile of the drug. A significant decrease in migraine headache is observed within 30 minutes after taking the drug. Data from clinical studies confirm that Excedrin® is an adequate and rational choice for the treatment of mild to moderate migraine headache, its effectiveness exceeds that of NSAID monotherapy [31], and in some cases is not inferior to triptans [7].

Literature

1. Lipton R. B., Bigal M. E., Steiner T. J., Silberstein S. D., Olesen J. Classification of primary headaches // Neurology. 2004. 63: 427–435.
2. Stovner L. J., Hagen K. Prevalence, burden, and cost of headache disorders // Curr. Opin. Neurol. 2006.19:281–285.
3. Olesen J., Gustavsson A., Svensson M., Wittchen H. U., Jonsson B. The economic cost of brain disorders in Europe // Eur. J. Neurol. 2012.19: 155–162.
4. Leonardi M., Steiner T. J., Scher A. T., Lipton R. B. The global burden of migraine: measuring disability in headache disorders with WHO’s Classification of Functioning, Disability and Health (ICF) // J. Headache Pain. 2005.6:429–440.
5. Lipton R. B., Newman L. C., Solomon S. Over-the-counter medication and treatment of migraine // Headache. 1994; 34:547–548.
6. Aicher B., Kraupp O. Effectiveness of fixed analgesic combinations exemplified by Thomapyrin® // Wien Klin Wochenschr. 1996; 108:219–233.
7. Goldstein J. et al. Acetaminophen, Aspirin, and Caffeine versus Sumatriptan Succinate in early treatment of migraine: results from the ASSET trial // Headache. 2005; 45:973–982.
8. Moskowitz M. A. The neurobiology of vascular head pain. Ann. Neurol. 1984.16:157–168.
9. Pietrobon D., Striessnig J. Neurobiology of migraine. Nat. Rev. neurosci. 2003. 4: 386–398.
10. Olesen J., Burstein R., Ashina M., Tfelt-Hansen P. Origin of pain in migraine: evidence for peripheral sensitization // Lancet Neurol. 2009.8:679–690.
11. Levy D. Migraine pain and nociceptor activation – where do we stand? // header. 2010. 50: 909–916.
12. Waeber C., Moskowitz M. A. Migraine as an inflammatory disorder // Neurology. 2005. 64: S9–15.
13. Levy D. Migraine pain, meningeal inflammation, and mast cells // Curr. Pain Headache Rep. 2009. 13:237–240.
14. Levy D. Endogenous mechanisms underlying the activation and sensitization of meningeal nociceptors: the role of immuno-vascular interactions and cortical spreading depression. Curr. Pain Headache Rep. 2012. 16: 270–277.
15. Edelmayer R. M., Vanderah T. W., Majuta L., Zhang E. T., Fioravanti B. et al. Medullary pain facilitating neurons mediate allodynia in headache-related pain // Ann. Neurol. 2009. 65: 184–193.
16. Burstein R., Cutrer M. F., Yarnitsky D. The development of cutaneous allodynia during a migraine attack: clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine // Brain. 2000. 123 (Pt. 8): 1703–1709.
17. Reuter U., Bolay H., Jansen-Olesen I., Chiarugi A., Sanchez del Rio M. et al. Delayed inflammation in rat meninges: implications for migraine pathophysiology // Brain. 2001. 124: 2490–2502.
18. Nicoletti P., Trevisani M., Manconi M., Gatti R., De Siena G. et al. Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig // Cephalalgia. 2008.28:9–17.
19. Nassini R., Materazzi S., Vriens J., Prenen J., Benemei S. et al. The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system // Brain. 2012. 135: 376–390.
20. Noseda R., Kainz V., Jakubowski M., Gooley J. J., Saper C. B. et al. A neural mechanism for exacerbation of headache by light // Nat. neurosci. 2010. 13: 239–245.
21. Tfelt-Hansen P., Block G., DahloEf C. et al. Guidelines for controlled trials of drugs in migraine: second edition // Cephalalgia. 2000; 20:765–786.
22. Evers S., Afra J., Frese A. et al. EFNS guideline on the drug treatment of migraine — revised report of an EFNS task force // European Journal of Neurology. 2009, 16:968–981.
23. Hersh E. V., Moore P. A., Ross G. L. Over-the-counter analgesics and antipyretics: a critical assessment // Clin Ther. 2000; 22:500–548.
24. Laska E. M., Sunshine A., Mueller F., Elvers W. B., Siegel C., Rubin A. Caffeine as an analgesic adjuvant // JAMA. 1984; 251: 1711–1718.
25. Camann W. R., Murray R. S., Mushlin P. S., Lambert D. H. Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial // Anesth Analg. 1990; 70:181–184.
26. Lipton R. B., Stewart W. F., Ryan R. E., Saper J., Silberstein S., Sheftell F. Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind randomized, placebo controlled trials // Arch Neurol. 1998; 55:210–217.
27. Silberstein S. D. Migraine symptoms: Results of a survey of self-reported migraineurs // Headache. 1995; 35:387–396.