naproxen and sumatriptan

Action and Spectrum

Actions and spectrum: 

naproxen: 

• Action: naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that works by inhibiting the enzymes called cyclooxygenases (COX-1 and COX-2). By blocking these enzymes, naproxen reduces the production of prostaglandins, which are responsible for promoting inflammation, pain, and fever. 
• Spectrum of Use: naproxen is primarily used for the relief of pain, inflammation, and fever associated with various conditions, including arthritis (such as osteoarthritis and rheumatoid arthritis), musculoskeletal injuries, menstrual cramps, and other inflammatory conditions. 

sumatriptan: 

• Action: sumatriptan is a selective serotonin receptor agonist that specifically targets serotonin (5-HT1B/1D) receptors. By activating these receptors, sumatriptan causes vasoconstriction and inhibits the release of neuropeptides involved in pain transmission, such as substance P. It is thought to relieve migraines by reversing the abnormal dilation of blood vessels in the brain and reducing the inflammation associated with migraines. 
• Spectrum of Use: sumatriptan is primarily used in the acute treatment of migraines and cluster type of headaches. It relieves the pain, nausea, and other symptoms associated with these conditions. sumatriptan is not intended for preventive use and does not treat the underlying causes of migraines or cluster headaches. 

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

naproxen carries a black box warning for an increased risk of cardiovascular diseases, which may be higher with long-term use or in patients with pre-existing cardiovascular conditions.

sumatriptan carries a black box warning for the risk of coronary artery vasospasm, myocardial ischemia, and other serious cardiac events. It is contraindicated in coronary artery disease, uncontrolled hypertension, or other significant cardiovascular conditions. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Allergy or Hypersensitivity: naproxen is contraindicated in individuals who have a known hypersensitivity or allergic reaction to naproxen or other NSAIDs (nonsteroidal anti-inflammatory drugs), such as aspirin or ibuprofen. 
• Active Bleeding or Ulcers: naproxen should not be used in individuals with active gastrointestinal bleeding or a history of peptic ulcers, as it may increase the risk of further bleeding or ulceration. 
• Coronary Artery Bypass Graft Surgery: naproxen is contraindicated for recent coronary artery bypass graft (CABG) surgery, as it may increase the risk of cardiovascular events and impair the healing process. 
• Ischemic Heart Disease: sumatriptan is contraindicated in individuals with ischemic heart disease, including angina (chest pain) and history of myocardial infarction (heart attack), due to the risk of coronary artery vasospasm and cardiac events. 
• Transient Ischemic Attack (TIA) or stroke: sumatriptan is contraindicated in individuals with stroke or transient ischemic attack (TIA) due to the increased risk of cerebrovascular events.

Caution: 

• Gastrointestinal Effects: naproxen can cause stomach ulcers, bleeding, and perforation, particularly in elderly individuals or those with a history of gastrointestinal disorders. Caution should be exercised, and the lowest effective dose should be used to minimize these risks. 
• Renal Effects: naproxen may affect kidney function and should be used with caution in individuals with pre-existing renal impairment, heart failure, or those taking diuretics or other medications that impact kidney function. 
• Serotonin Syndrome: sumatriptan, as a serotonin receptor agonist, has the potential to cause serotonin syndrome, a rare but serious condition. Caution should be exercised, especially when using sumatriptan with other serotonergic medications like selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. 
• Hemiplegic or Basilar Migraine: sumatriptan is contraindicated in individuals with hemiplegic or basilar migraine due to the potential risk of vasospasm and ischemic events. If there is uncertainty about the diagnosis, caution is advised. 
• Hepatic Impairment: Individuals with moderate to severe hepatic impairment may have delayed clearance of sumatriptan. Caution and lower initial doses may be necessary in such cases. 

Comorbidities: 

• Arthritis: naproxen is commonly used to treat osteoarthritis and rheumatoid arthritis. Comorbidities associated with arthritis include joint deformities, joint inflammation, and systemic complications. 
• Cardiovascular Disease: Individuals with cardiovascular disease, including hypertension, heart failure, or a history of heart attack or stroke, may have an increased risk of adverse cardiovascular events when using naproxen. Caution and careful monitoring are advised in such cases. 
• Gastrointestinal Disorders: naproxen can cause gastrointestinal side effects, such as stomach ulcers, bleeding, and perforation. Comorbidities associated with gastrointestinal disorders, such as peptic ulcers, gastritis, or gastrointestinal bleeding, may require extra caution when using naproxen. 
• Migraine: sumatriptan is primarily used for the acute treatment of migraines. Comorbidities associated with migraines may include other headache disorders, psychiatric conditions like depression or anxiety, and certain medical conditions such as fibromyalgia or irritable bowel syndrome (IBS). 
• Hypertension: High blood pressure (hypertension) is a common comorbidity in individuals using sumatriptan. The vasoconstrictive properties of sumatriptan may increase blood pressure, and monitoring is important, especially in those with uncontrolled hypertension. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Yes  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

naproxen is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory, and antipyretic properties. It acts by inhibiting the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are responsible for the synthesis of prostaglandins involved in pain and inflammation. By blocking these enzymes, naproxen reduces the production of prostaglandins, leading to decreased pain, inflammation, and fever. naproxen is well-absorbed orally, and its effects typically last for several hours. 

sumatriptan is a selective serotonin receptor agonist, specifically targeting serotonin (5-HT1B/1D) receptors. It works by activating these receptors, leading to vasoconstriction (constriction of blood vessels) and inhibition of neuropeptide release involved in pain transmission, such as substance P. By causing vasoconstriction and reducing inflammation in the brain, sumatriptan helps relieve the symptoms of migraines. sumatriptan is available in various formulations, including oral, nasal spray, and injection, with different rates of absorption and onset of action.  

Pharmacodynamics: 

• Anti-inflammatory Action: naproxen reduces inflammation by inhibiting the synthesis of inflammatory prostaglandins, thereby decreasing vasodilation, edema formation, and leukocyte infiltration at the site of inflammation. 
• Analgesic Action: naproxen has analgesic properties, primarily by reducing the production of prostaglandins that sensitize pain receptors and mediate pain signals. 
• Antipyretic Action: naproxen lowers fever by inhibiting the production of prostaglandins in the hypothalamus, which is responsible for regulating body temperature. 
• Vasoconstriction: sumatriptan binds to serotonin receptors on blood vessels, leading to vasoconstriction, particularly in the cranial vessels. This helps to alleviate the dilation of blood vessels during a migraine attack. 
• Inhibition of Neuropeptide Release: sumatriptan inhibits the release of various neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP), which are involved in transmitting pain signals. 
• Suppression of Neurogenic Inflammation: sumatriptan reduces the release of pro-inflammatory mediators from trigeminal nerves, helping to suppress neurogenic inflammation associated with migraines.

Pharmacokinetics: 

naproxen:  

• Absorption: naproxen is well-absorbed after oral administration. Peak plasma concentration is reached within 2 to 4 hours after ingestion. 
• Distribution: naproxen is highly bound to plasma proteins, primarily albumin. It has a moderate volume of distribution, indicating distribution into extravascular tissues. 
• Metabolism: naproxen undergoes extensive hepatic metabolism, primarily through the cytochrome P450 enzyme system, particularly CYP2C9. It undergoes phase II conjugation to form inactive metabolites. 
• Excretion: The majority of naproxen and its metabolites are excreted in the urine. The elimination half-life of naproxen is around 12 to 17 hours in healthy adults.

sumatriptan: 

• Absorption: sumatriptan is available in different formulations, including oral, subcutaneous injection, and nasal spray. The oral formulation has low bioavailability due to significant first-pass metabolism. The subcutaneous and nasal spray formulations provide more rapid absorption. 
• Distribution: sumatriptan has moderate protein binding, primarily to plasma proteins. It has a small volume of distribution, indicating limited distribution into tissues. 
• Metabolism: sumatriptan is extensively metabolized in the liver through various pathways, including oxidation via monoamine oxidase-A (MAO-A) and subsequent conjugation. 
• Excretion: Both sumatriptan and its metabolites are primarily eliminated in the urine. The elimination half-life of sumatriptan ranges from 1.5 to 2.5 hours, while the half-life of N-desmethylsumatriptan is longer, ranging from 2.5 to 4 hours. 

Adminstartion

Administration: 

naproxen is typically administered orally in the form of tablets or capsules. Taking naproxen with food or milk is recommended to help decrease the risk of gastrointestinal side effects. sumatriptan is available in different formulations, including oral tablets, subcutaneous injections, and nasal sprays. 

• Oral Tablets: sumatriptan tablets are swallowed with water. The dosage and timing instructions should be followed as the healthcare professional prescribes. 
• Subcutaneous Injections: sumatriptan injections are administered subcutaneously (under the skin) using a pre-filled syringe or an autoinjector device. The injection is typically given into the thigh or abdomen. It is important to carefully read and follow the instructions provided with the injection device or as directed by the healthcare professional. 
• Nasal Spray: sumatriptan nasal spray is administered intranasally by spraying the prescribed dose into one nostril. The specific instructions for using the nasal spray should be followed as provided by the healthcare professional or as stated in the product packaging. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: naproxen and sumatriptan 

Pronounced: (nuh-PROK-sen-and- soo-muh-TRIP-tan)  

Why do we use naproxen and sumatriptan? 

• Pain Relief: It is commonly used to relieve pain associated with conditions such as headaches, menstrual cramps, dental pain, musculoskeletal pain (e.g., arthritis, sprains), and other acute or chronic painful conditions. 
• Inflammation Reduction: naproxen helps reduce inflammation associated with conditions like rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, and gout. 
• Fever Reduction: naproxen can also be used as an antipyretic to lower fever. 
• Migraine Relief: sumatriptan helps alleviate the symptoms of migraines, such as severe headache, nausea, sensitivity to light and sound, and other associated symptoms. 
• Cluster Headache Relief: sumatriptan also effectively treats cluster headaches, which are severe, recurrent headaches that occur in clusters over a specific period.