Excedrin (Tablets) Instructions for Use

Marketing Authorization Holder

GlaxoSmithKline Healthcare, JSC (Russia)

Manufactured By

GSK Consumer Health, Inc. (USA)

Trademark Owner

GlaxoSmithKline Group of Companies

ATC Code

N02BA71 (Acetylsalicylic acid in combination with psycholeptics)

Active Substances

Caffeine (Ph.Eur.)

Paracetamol (Rec.INN)

Acetylsalicylic acid (Ph.Eur.)

Dosage Form

Excedrin

Film-coated tablets, 250 mg+250 mg+65 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oblong, with an engraving “E” on one side; on the cross-section – a core of white or almost white color.

Excipients: hypromellose – 5 mg, microcrystalline cellulose – 100 mg, stearic acid – 2.5 mg.

Film coating composition carnauba wax – 0.08 mg, white film coating material – 4.48 mg (hypromellose, titanium dioxide, propylene glycol, povidone, sorbitan laurate, polysorbate-20, mineral oil, benzoic acid, simethicone emulsion, brilliant blue dye).

2 pcs. – multilayer sachets (1) – cardboard packs.
10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
24 pcs. – bottles (1) – cardboard packs.
50 pcs. – bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Combination analgesic-antipyretic

Pharmacotherapeutic Group

Combined analgesic agent (NSAID + non-narcotic analgesic agent + psychostimulant agent)

Pharmacological Action

Excedrin^® is a combined preparation containing Paracetamol, Acetylsalicylic acid, and Caffeine.

Paracetamol has analgesic, antipyretic, and very weak anti-inflammatory effects, which is associated with its influence on the thermoregulation center in the hypothalamus and its weak ability to inhibit the synthesis of prostaglandins in peripheral tissues.

Acetylsalicylic acid has analgesic, antipyretic, and anti-inflammatory effects. It quickly relieves pain, especially that caused by an inflammatory process, and also moderately inhibits platelet aggregation and slows down the process of thrombus formation, improving microcirculation in the focus of inflammation.

Caffeine increases the reflex excitability of the spinal cord, stimulates the respiratory and vasomotor centers, dilates blood vessels of skeletal muscles, brain, heart, kidneys, and reduces platelet aggregation. It reduces drowsiness, feeling of fatigue, and increases mental and physical performance. In this combination, Caffeine in a small dose practically does not have a stimulating effect on the CNS, but helps to normalize the tone of cerebral vessels and accelerate blood flow in them.

Pharmacokinetics

Paracetamol is easily absorbed from the gastrointestinal tract, C_max in blood plasma is detected in the interval from 30 min to 2 h after administration. Paracetamol is metabolized in the liver and excreted by the kidneys, mainly in the form of glucuronides and sulfate conjugates. Less than 5% of paracetamol is excreted unchanged. The duration of T_1/2 varies from 1 to 4 h. Binding to plasma proteins is insignificant at usual therapeutic doses, but increases as the dose increases. The hydroxylated metabolite, formed in small amounts in the liver under the influence of mixed oxidases and usually detoxified by binding to glutathione, can accumulate in paracetamol overdose and cause liver damage.

Acetylsalicylic acid is rapidly and completely absorbed, undergoes rapid hydrolysis in the gastrointestinal tract, liver, and blood to form salicylates, which undergo further metabolism, mainly in the liver.

Caffeine is completely and rapidly absorbed. Maximum concentrations are observed in the interval from 5 to 90 min after administration on an empty stomach. In adults, elimination occurs almost entirely through hepatic metabolism. There is pronounced variability in individual elimination values in adults. The average T_1/2 from blood plasma is 4.9 h in the range of 1.9-12.2 h. Caffeine is distributed in all body fluids. The binding of caffeine to plasma proteins is 35%. Caffeine is almost completely metabolized by oxidation, demethylation, and acetylation and is excreted by the kidneys. The main metabolites are 1-methylxanthine, 7-methylxanthine, 1,7-dimethylxanthine.

Indications

Pain syndrome of moderate and mild intensity of various origins:

• Headache;
• Migraine;
• Toothache;
• Neuralgia;
• Arthralgia and myalgia (pain in muscles and joints);
• Algodysmenorrhea (pain during menstruation).

ICD codes

Dosage Regimen

The preparation is taken orally during or after meals.

Adults and adolescents from 15 years old take 1 tablet every 4-6 hours.

At the first signs of migraine, take 2 tablets.

The average daily dose is 3-4 tablets per day, the maximum daily dose is 6 tablets per day.

After taking 2 tablets, relief from headache and other types of pain usually occurs quickly – within 15 minutes, for migraine relief usually occurs within 30 minutes.

For pain syndrome, the preparation should not be taken for more than 5 days without consulting a doctor. For migraine, the preparation should not be taken for more than 3 days without consulting a doctor.

Adverse Reactions

Gastralgia, nausea, vomiting, hepatotoxicity, nephrotoxicity, erosive and ulcerative lesions of the gastrointestinal tract, allergic reactions, tachycardia, increased blood pressure, bronchospasm.

With prolonged use – dizziness, headache, visual disturbances, tinnitus, decreased platelet aggregation, hypocoagulation, hemorrhagic syndrome (nosebleed, gum bleeding, purpura, etc.), kidney damage with papillary necrosis, deafness, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), Reye’s syndrome in children (hyperpyrexia, metabolic acidosis, disorders of the nervous system and psyche, vomiting, impaired liver function).

Contraindications

• Hypersensitivity to any of the components in the preparation;
• Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;
• Gastrointestinal bleeding;
• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including in history);
• Surgical interventions accompanied by bleeding;
• Hemophilia;
• Hemorrhagic diathesis;
• Hypoprothrombinemia;
• Severe arterial hypertension;
• Portal hypertension;
• Severe coronary artery disease;
• Glaucoma;
• Vitamin K deficiency;
• Renal failure;
• Simultaneous use of other preparations containing Paracetamol, acetylsalicylic acid or another non-steroidal anti-inflammatory agent;
• Glucose-6-phosphate dehydrogenase deficiency;
• Pregnancy;
• Lactation;
• Increased excitability;
• Sleep disorders;
• Children under 15 years of age (risk of developing Reye’s syndrome in children with hyperthermia against the background of viral diseases).

Use with caution in gout, liver diseases, headaches associated with head trauma, taking anticoagulants, hypoglycemic agents, gout or arthritis, as well as when taking preparations containing acetylsalicylic acid or other analgesic and antipyretic components simultaneously.

Use in Pregnancy and Lactation

Although acetylsalicylic acid can be used in the second trimester of pregnancy, the safety of this combination in pregnant and breastfeeding women has not been studied, therefore the preparation is contraindicated in pregnant women (in all trimesters) and breastfeeding women.

Use in Renal Impairment

The use of the preparation is prohibited in renal failure.

Pediatric Use

The use of the preparation is prohibited in children under 15 years of age (risk of developing Reye’s syndrome in children with hyperthermia against the background of viral diseases).

Special Precautions

If symptoms persist after taking the preparation, worsen, or new symptoms appear, you should immediately consult a doctor. When taking the preparation at the recommended dose, the amount of caffeine entering the body is the same as contained in one cup of coffee, so the consumption of caffeine-containing products should be reduced during treatment with this preparation to avoid the development of nervous excitement, irritability, insomnia, and rapid heartbeat due to caffeine overdose. If an overdose is suspected, you should immediately seek medical help, even if there are no symptoms. You should refrain from drinking alcohol while taking the preparation due to an increased risk of liver damage and gastrointestinal bleeding. Since Acetylsalicylic acid slows down blood clotting, a patient who is to undergo surgery should inform the doctor in advance about taking the preparation. Acetylsalicylic acid in low doses reduces the excretion of uric acid, which is why in predisposed patients the preparation can provoke an attack of gout. With prolonged use of the preparation, monitoring of peripheral blood and the functional state of the liver is necessary.

Effect on the ability to drive vehicles and work with mechanisms

No reports of the effect of the preparation on the ability to drive a car and work with mechanisms have been received.

Overdose

Symptoms due to the presence of paracetamol (when taken in doses of more than 10-15 g/day): within the first 24 hours, pallor of the skin, nausea, vomiting, anorexia, abdominal pain, impaired glucose metabolism, metabolic acidosis. Symptoms of impaired liver function may appear 12-48 hours after overdose. In severe overdose – liver failure with progressive encephalopathy, coma, death; acute renal failure with tubular necrosis (including in the absence of severe liver damage); arrhythmia, pancreatitis. Hepatotoxic effect in adults manifests when taking 10 g or more.

Symptoms due to the presence of acetylsalicylic acid (when taken in doses of more than 150 mg/kg): in mild intoxications – nausea, vomiting, tinnitus, visual impairment, dizziness, severe headache. In severe poisoning – central hyperventilation of the lungs (shortness of breath, suffocation, cyanosis, cold sticky sweat, respiratory paralysis), respiratory acidosis. The greatest risk of developing chronic intoxication is noted in children and the elderly when taking more than 100 mg/kg/day for several days. In case of moderate and severe poisoning, hospitalization is necessary.

Symptoms due to the presence of caffeine (when taken in doses of more than 300 mg/day): gastralgia, agitation, anxiety, excitement, motor restlessness, confusion, delirium, dehydration, tachycardia, arrhythmia, hyperthermia, frequent urination, headache, increased tactile or pain sensitivity, tremor or muscle twitching; nausea and vomiting, sometimes with blood; ringing in the ears, epileptic seizures (with acute overdose – tonic-clonic). Treatment: monitoring of acid-base status and electrolyte balance. Depending on the state of metabolism – administration of sodium bicarbonate, sodium citrate or sodium lactate. Increasing alkalinity enhances the excretion of acetylsalicylic acid by alkalinizing the urine. Gastric lavage within the first 4 hours, induction of vomiting, intake of activated charcoal, laxative medications, administration of SH-group donors and precursors of glutathione synthesis methionine within 8-9 hours after overdose and acetylcysteine – within 8 hours.

Drug Interactions

The preparation may enhance the effect of heparin, indirect anticoagulants, reserpine, steroid hormones, and hypoglycemic medications.

Simultaneous use with other NSAIDs, methotrexate increases the risk of side effects. Reduces the effectiveness of spironolactone, furosemide, antihypertensive medications, as well as anti-gout drugs that promote the excretion of uric acid. Barbiturates, rifampicin, salicylamide, antiepileptic drugs and other inducers of liver microsomal enzymes contribute to the formation of toxic metabolites of paracetamol that affect liver function. Metoclopramide accelerates the absorption of paracetamol. Under the influence of paracetamol, the half-life of chloramphenicol increases 5 times. With repeated use, Paracetamol may enhance the effect of anticoagulants (coumarin derivatives).

Simultaneous intake of paracetamol, acetylsalicylic acid and alcoholic beverages increases the risk of hepatotoxic effects. Caffeine accelerates the absorption of ergotamine.

Storage Conditions

The preparation should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Do not use after the expiration date indicated on the package.

Dispensing Status

The preparation is approved for use as an over-the-counter product.

NR15MU0542 May 2015

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.