Sumatriptan and Naproxen Sodium: Uses, Side Effects, and Precautions

Overview

A combination of Sumatriptan, a selective serotonin receptor agonist, and Naproxen sodium, a nonsteroidal anti-inflammatory drug (NSAID), is a migraine relief medication (severe throbbing headache) with or without aura (sensory or visual disturbances that occur before migraine) in adult patients and children over 12 years of age. Studies have demonstrated the multi-mechanism action and benefits of combining a triptan and an analgesic antimigraine treatment over monotherapy. The US Food and Drug Administration (USFDA) authorized the combination of Naproxen sodium and Sumatriptan on April 15, 2008.

How Does the Combination of Sumatriptan and Naproxen Sodium Combination Work?

Sumatriptan is a selective (5HT1-receptor) agonist that relieves headaches by narrowing the widened blood vessels. Naproxen is an NSAID that blocks the release of certain chemicals and reduces symptoms such as pain, fever, and inflammation caused by migraine. However, it must be used only if a diagnosis of migraine is confirmed.

Who Can Use Sumatriptan and Naproxen Sodium?

Sumatriptan and Naproxen sodium combination is indicated for the management of acute migraine with or without aura in adults and children over 12 years of age.

What Are the Contraindications of Sumatriptan and Naproxen Sodium?

• Sumatriptan and Naproxen sodium combination is not recommended for cluster headaches or the prevention of migraine attacks.

• It must be avoided in pregnancy, especially during the third trimester.

• It is not indicated for individuals with a history of hypersensitivity (severe allergic reactions), lactating women, or children below 12 years of age.

• It is not recommended for elderly patients, especially those with hepatic or renal disorders.

• Sumatriptan and Naproxen sodium combination is also contraindicated in patients with uncontrolled hypertension (increased blood pressure), history of asthma (chronic lung disease), stroke, hemiplegic (migraine with one-sided muscle weakness), or basilar migraine (migraine that begins in the brainstem), urticaria (raised itchy rash), allergic reactions to Aspirin or other NSAIDs, ischemic coronary artery disease (narrowing of coronary arteries), peripheral vascular disease (blood circulation disorder), and ischemic bowel disease (vascular disorder of the gastrointestinal tract).

What Are the Available Doses, Dosage Forms, and Usage Guidelines?

The drug is available in 10 mg of Sumatriptan/60 mg (milligrams) Naproxen and 85 mg of Sumatriptan/500 mg Naproxen tablets; it can be taken with or without food. However, the tablet should be whole, not split, crushed, or chewed.

• Adults: The recommended dose of the Sumatriptan and Naproxen sodium combination is one 85/500 mg tablet. The recommended dose in 24 hours is two tablets maximum, to be taken at least two hours apart.

• Children: The recommended dose for children between 12 and 17 years is one tablet of 10/60 mg; the maximum dose recommended in 24 hours is one tablet of 85/500 mg of the Sumatriptan-Naproxen combination.

• Patients With Hepatic Disorders: The maximum dose is one 10/60 mg tablet over 24 hours.

Warnings and Precautions

• Anaphylactic reactions (severe allergic reactions) can occur in some patients with hypersensitivity to Sumatriptan or Naproxen, in patients with Aspirin-sensitive asthma, or without prior exposure to the Sumatriptan-Naproxen combination, which can be severe or life-threatening. Therefore, this combination drug is contraindicated in such patients, and appropriate treatment measures must be considered if hypersensitivity reactions are observed.

• Patients who have coronary artery bypass graft surgery or ischemic or vasospastic coronary artery disease should not use Sumatriptan and Naproxen together (CABG) (heart bypass surgery) due to the risk of serious cardiovascular events.

• NSAIDs, including Naproxen, can cause gastrointestinal adverse events such as inflammation, ulceration, bleeding, and perforation of the stomach or intestine, which can occur in some patients, especially those with a known history of peptic ulcer disease.

• Ventricular tachycardia (abnormal heart rhythm), ventricular fibrillation (irregular heartbeats), or disturbances in cardiac rhythm may occur in some patients using 5-HT agonist agents. Therefore, the drug must be avoided in patients with arrhythmias or other cardiac disorders.

• It may cause cerebral hemorrhage (bleeding in the brain), subarachnoid hemorrhage (bleeding in the subarachnoid space), or stroke in some patients.

• NSAIDs can cause an elevation of liver enzymes or abnormalities in liver function. Therefore, the drug must be discontinued if any signs and symptoms of liver disease develop or if persistent abnormal liver test values are obtained.

• It can cause a significant elevation in blood pressure or increase the risk of cardiovascular events.

• Serotonin syndrome (increased serotonin levels) symptoms such as agitation, autonomic instability, hallucinations, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting can occur in some patients. Hence, the drug must be discontinued if serotonin syndrome is suspected.

• The Sumatriptan-Naproxen combination is not recommended in pregnant women as it can cause premature closure of the ductus arteriosus.

• NSAIDs may cause bleeding and anemia in some patients. Hence, these patients must be monitored immediately if signs and symptoms are suspected.

• Sumatriptan can cause seizures (uncontrolled body movements) in some patients; therefore, this drug must be used with caution in patients with a history of epilepsy or any other associated conditions.

• Long-term NSAID treatment can cause gastrointestinal bleeding, renal injury, or hepatotoxicity (liver injury). Hence, the complete blood count and chemistry profile must be monitored periodically.

What Are the Common Side Effects of Sumatriptan and Naproxen Sodium?

Adverse effects of Sumatriptan and Naproxen sodium include:

• Tingling or pricking sensation.

• Chest pain and discomfort.

• Neck, throat, and jaw pain.

• Fast or irregular heartbeat.

• Dizziness.

• Nausea.

• Hot flashes.

• Indigestion.

• Nausea and vomiting.

• Sleepiness or drowsiness.

• Stomach upset or discomfort.

• Muscle tightness.

For Patients

What Is Migraine With or Without Aura?

• A migraine is a headache that causes severe throbbing pain on one side of the head. It is a genetically influenced complex condition often accompanied by sensitivity to light and sound, nausea, and vomiting.

• It is mainly caused by abnormal brain activity triggered by various chemicals and nerve pathways affecting the brain's blood flow. It first appears between 10 and 45 but can sometimes begin a few years earlier or later.

• Migraines usually run in families, are more common in women than men, and can occur with or without an aura (a sequence of sensory or visual disturbances just before a migraine attack). Symptoms include blind spots, flashes of light, tingling sensations in the head or face, speech difficulties, dizziness, confusion, zigzag lines in the vision, and others.

• Some of the factors that trigger a migraine attack include loud sounds, bright lights, strong odors, stress, tobacco, sudden changes in weather, lack of sleep, low blood sugar levels, motion sickness, anxiety, depression, skipping meals, certain medications, hormonal changes, etc. Migraines can be managed by drugs, over-the-counter (OTC) analgesics, lifestyle changes to prevent migraine triggers, adequate hydration, relaxation techniques, exercises, and following a regularly scheduled diet and sleep routine.

What Is Sumatriptan and Naproxen Sodium?

Sumatriptan-Naproxen is a combination drug of two medicines used for the treatment of acute migraine with or without an aura in individuals over 12 years of age. It is a prescription medicine and must be taken only if the diagnosis of migraine is confirmed. It must be taken as soon as an aura is experienced or exactly as prescribed by the doctor. However, it does not prevent future migraine attacks or reduce the frequency of the episodes.

How Effective Are Sumatriptan and Naproxen Sodium?

Sumatriptan belongs to a group of drugs called triptans that prevent the narrowing of blood vessels in the brain and relieve pain by acting on certain nerves in the brain. Naproxen is a non-steroidal anti-inflammatory drug that reduces pain, fever, and inflammation. The Sumatriptan-Naproxen combination provides consistent relief from migraine attacks and improves patient satisfaction and quality of life. It also reduces pill burden and improves adherence in some patients. Studies have demonstrated that this drug has significantly superior pain-relief properties, is well-tolerated among most patients, and offers clinical benefits over monotherapy.

How Should Sumatriptan and Naproxen Sodium Be Taken?

The Sumatriptan-Naproxen combination drug must be taken orally with or without food. The tablet must be taken as a whole and must not be split, crushed, or chewed. It must be taken exactly as prescribed by the doctor, as the dose is based on the patient's age, severity, response to the drug, and general health. If symptoms do not improve or are only partly relieved, the doctor must be consulted immediately.

What Are the Side Effects of Sumatriptan and Naproxen Sodium?

Some of the side effects of Sumatriptan and Naproxen sodium include:

• Stomach and intestinal problems.

• Liver and kidney problems.

• Asthma attacks.

• Anemia (low red blood cells).

• Increase in blood pressure.

• Fever.

• Swelling.

• Constipation.

• Weight loss.

• Nausea and vomiting.

• Diarrhea.

What Must the Patient Inform the Doctor Before Taking the Drug?

• Patients must inform the doctor if they are suffering from hypertension, high cholesterol, diabetes, asthma, epilepsy, obesity, kidney, liver, or heart problems, or any other medical conditions before starting the treatment.

• Before taking the treatment, patients must tell the doctor if they are allergic to Sumatriptan, Naproxen, NSAIDs, or other medications.

• Before taking Sumatriptan-Naproxen, female patients must be informed if they are pregnant, planning a pregnancy, or breastfeeding.

• Before starting treatment, patients must inform the doctor if they take any vitamins, herbal or nutritional supplements, over-the-counter drugs, or other medications.

What Are the Precautionary Measures to Be Followed While Taking the Drug?

• Sumatriptan-Naproxen can increase the chance of a heart attack or stroke that can be life-threatening. The risk may be higher with longer use of NSAIDs or if the dose is increased.

• Sumatriptan-Naproxen must not be used before and after coronary artery bypass graft surgery (CABG).

• Sumatriptan-Naproxen must be stopped if the patient experiences chest discomfort, chest pain or tightness, throat, neck, or jaw pain, shortness of breath, nausea, vomiting, lightheadedness, slurred speech, and weakness. The doctor must be consulted immediately if any of these symptoms are observed.

• Sumatriptan-Naproxen may cause ulcers and bleeding in the stomach or intestine at any time during the treatment. The risk is higher if the patient smokes, consumes alcohol, or has a history of stomach ulcers, intestinal bleeding, advanced liver disease, or bleeding problems.

• Sumatriptan-Naproxen can cause severe allergic reactions that can be life-threatening; therefore, the drug must be stopped immediately if the patient experiences blisters, rash, breathing problems, reddening of the skin, swelling of the lips, tongue, throat, sudden wheezing, or any other severe adverse reactions.

Overdose

Animal studies have shown that an overdose of Sumatriptan can be fatal or life-threatening or can be associated with tremors, inactivity, paralysis, cyanosis, salivation, erythema of the extremities, abnormal respiration, etc. Symptoms following acute overdoses of NSAIDs have been limited to nausea, vomiting, gastrointestinal bleeding, lethargy, drowsiness, and epigastric pain. Symptomatic and supportive medical care must be considered immediately following an NSAID overdose.

Storage

Sumatriptan-Naproxen tablets must be stored at 25 degrees Celsius (77 degrees Fahrenheit) in their original container, away from excess heat and moisture and out of the reach of children.

For Doctors

Pharmacological Aspects of Sumatriptan and Naproxen Sodium

Mechanism of Action

Sumatriptan is a 5-HT agonist that exerts its therapeutic effects by its agonist action on the sensory nerves of the trigeminal system and intracranial blood vessels. This results in cranial vessel constriction and inhibits neuropeptide release. Naproxen is an NSAID and a potent inhibitor of prostaglandin synthesis. It sensitizes the afferent nerves and decreases prostaglandins in peripheral tissues, thus reducing pain and inflammation. The exact mechanism of action of the Sumatriptan and Naproxen combination has yet to be completely understood. However, the drug exhibits analgesic, antipyretic, and anti-inflammatory properties as it blocks cyclooxygenase (COX) inhibitors such as COX-1 and COX-2.

Pharmacodynamics

Sumatriptan-Naproxen is a fixed-dose combination of a serotonin 5-HT 1B/1D receptor agonist and an NSAID for the acute management of migraine with or without aura in individuals over the age of 12 years. Clinical trials have demonstrated that the patients were significantly pain-free after two hours of taking Sumatriptan-Naproxen compared to a placebo. This combination was also proven effective compared to the individual components regarding pain-free response.

Pharmacokinetics

Absorption: The Sumatriptan-Naproxen combination has a similar mean plasma concentration to that of 100 mg tablets of Sumatriptan alone. The time taken to achieve the maximum concentration of Sumatriptan-Naproxen was about one hour. The bioavailability of Sumatriptan and Naproxen is approximately 15 percent and 95 percent, respectively.

Distribution: The drug is approximately 14 to 21 percent bound to plasma proteins, and the apparent volume of distribution is about 2.7 L/kg (liters per kilogram).

Metabolism: Sumatriptan is metabolized by the enzyme monoamine oxidase, and Naproxen is extensively metabolized to form 6-0-desmethyl naproxen.

Excretion: The elimination half-life of Sumatriptan is about two hours, and approximately 60 percent and 40 percent of radiolabeled C-sumatriptan is excreted in the urine and feces, respectively. The clearance of Naproxen is approximately 0.13 mL/min/kg (milliliter/minute/kilogram), and about 95 percent of Naproxen and its metabolites are excreted in the urine.

Drug Interactions

Some of the drugs that interact with Sumatriptan-Naproxen include:

• Methotrexate.

• Warfarin.

• Prednisone.

• Dexamethasone

• Cyclosporine.

• Blood pressure medications.

• Diuretic drugs.

• Antidepressant medications.

• Benzodiazepine.

• Acetaminophen.

• Ergotamine.

• Naratriptan.

• Procarbazine.

• Rizatriptan.

• Zolmitriptan.

• Ketorolac.

• Ondansetron.

• Enalapril.

Clinical Studies

Several double-blind trials of Sumatriptan-Naproxen combination 85/500 mg in adults with migraine/acute trial system. Participants in the predominantly female (mean age 40) single tablet for moderate to severe pain reduction cohort rescue medication for 2 hours. Fewer patients had headache relief and remained free of pain for 24 hours with the combination compared to placebo, and a trend was found in the results.

In a concurrent study for children (12 years through 17 years), the active doses were either 85/500 mg, 10/60 mg, or 30/180 mg of Sumatriptan-Naproxen vs. Placebo. The 85/500M group had a reduction in phonophobia and photophobia associated with sustained pain-free status (2-24 hours) when compared to the placebo dose, showing a higher rate of cure.

Nonclinical Toxicology

• Carcinogenesis: The carcinogenic potential of Sumatriptan-Naproxen has not been evaluated. However, no evidence of tumorigenicity was observed in the individual components.

• Mutagenesis: Sumatriptan-Naproxen tested in combination or as individual components were negative in the in vivo micronucleus assay in mice and in in vitro bacterial reverse mutation assay.

• Impairment of Fertility: The effect of the Sumatriptan-Naproxen combination on fertility in animals has not been studied.

Specific Considerations: When to Avoid the Medication

• Pregnancy: Adequate and well-controlled studies of Sumatriptan-Naproxen have not been performed on pregnant women. Therefore, it must be avoided by pregnant women, especially during the third trimester.

• Lactation: Both Sumatriptan and Naproxen have been reported to be secreted in breast milk. Hence, they must be avoided during lactation to prevent potential adverse effects on the breastfed infant and consider the drug's importance to the mother.

• Pediatric Use: Sumatriptan-Naproxen is not recommended for children below the age of 12

• Geriatric Use: Elderly patients are at a higher risk for NSAID-associated serious adverse reactions compared to younger adults. Therefore, it is not recommended for elderly patients, especially those with cardiovascular, gastrointestinal, or renal disorders.

• Hepatic and Renal Impairment: Dose modification of Sumatriptan-Naproxen is preferred for hepatic disorders, and the drug is contraindicated for patients with severe hepatic impairment. However, serum creatinine levels must be periodically monitored (mild to moderate renal malfunction).

Key Takeaway From iCliniq

Sumatriptan and Naproxen sodium are combination treatments used to treat migraines. People have multiple strategies for immediate management and prevention of future migraine-related disruptions. We at iCliniq are here to provide you with all the necessary information about the drug. Talking to your healthcare provider will enable you to prevent migraines from controlling your daily existence.