diclofenac/misoprostol

Action and Spectrum

Actions and Spectrum: 

Actions: 

• diclofenac (Nonsteroidal Anti-inflammatory Drug – NSAID): diclofenac is an NSAID that inhibits the production of certain substances in the body called prostaglandins. Prostaglandins play a role in promoting inflammation, pain, and swelling. By inhibiting their production, diclofenac helps to reduce inflammation, relieve pain, and improve joint function. 
• misoprostol (Prostaglandin E1 Analog): misoprostol is a synthetic prostaglandin E1 analog. It works by promoting the protection of the stomach lining and reducing the production of stomach acid. This helps to decrease the risk of developing gastric ulcers and other gastrointestinal complications associated with NSAID use. 

Spectrum: 

• Anti-inflammatory effect: diclofenac/misoprostol effectively reduces inflammation like osteoarthritis and rheumatoid arthritis. It helps alleviate pain, swelling, and stiffness in the affected joints. 
• Analgesic effect: The medication inhibits the production of prostaglandins, which are involved in pain signaling and sensitization. 
• Gastrointestinal protection: misoprostol helps to protect the stomach lining and reduce the risk of developing gastric ulcers associated with NSAID use. This is particularly important because long-term use of NSAIDs can increase the risk of gastrointestinal complications. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Pyrexia (15%) 

Flushing (13%) 

Urticaria (13%) 

1-10% 

Hypertension (10%) 

Decreased oxygen saturation (8%) 

Hyperhidrosis (8%) 

Tachycardia (8%) 

Urticaria (8%) 

Cough (8%) 

Tachypnea (8%) 

Anaphylaxis (7%) 

Muscle twitching (7%) 

Chest discomfort (7%) 

Pallor (5%) 

Erythema (5%) 

Cyanosis (5%) 

Vomiting (5%) 

Rigors (5%) 

Myalgia (5%) 

Flushing (5%) 

Agitation (5%) 

Tremor (5%) 

Peripheral edema (3%) 

Pruritus (3%) 

Throat tightness (3%) 

Rash, papular (3%) 

<1% 

Fatigue 

Malaise 

Atrial fibrillation 

Congestive heart failure 

Chills 

Edema 

Myocardial infarction 

Syncope 

Dysphagia 

Enteritis 

Peptic ulcer 

Vaginitis 

Uterine cramping 

Ulcerative stomatitis 

Impotence 

Breast pain 

Dysmenorrhea 

Perineal pain 

Alopecia 

Glycosuria 

Black Box Warning

Black Box Warning: 

NSAIDs increase the risk of myocardial infarction, stroke, and severe CV thrombotic agents. They increase the risk with more extended usage. NSAIDs increase the risk of serious gastrointestinal events.

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 
• Pregnancy  
• Lactation 
• Peptic ulcer 

Cautions 

• Cardiovascular disease 
• Renal impairment 
• Hepatic impairment 
• Elderly population 

Pregnancy / Lactation

Pregnancy consideration:  

Not recommended for fertile females.  

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

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: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

• diclofenac has anti-inflammatory, and antipyretic properties. Its pharmacological effects are primarily mediated through inhibiting cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. COX enzymes synthesize prostaglandins, mediating pain, inflammation, and fever. 
• By inhibiting COX enzymes, diclofenac reduces the production of prostaglandins, leading to the alleviation of pain, suppression of inflammation, and reduction of fever. It mainly acts by inhibiting the action of COX-2, which is involved in the inflammatory response. 
• misoprostol is a synthetic prostaglandin E1 (PGE1) analog. It binds to specific receptors called prostaglandin E receptors (EP receptors) on the gastric parietal cells, activating adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) levels. This results in reduced secretion of gastric acid and increased production of protective mucus in the stomach. 

Pharmacodynamics: 

By inhibiting COX enzymes, diclofenac reduces the production of prostaglandins, leading to the alleviation of pain, suppression of inflammation, and reduction of fever. It mainly acts by inhibiting the action of COX-2, which is involved in the inflammatory response. 

misoprostol binds to specific receptors called prostaglandin E receptors (EP receptors) on the gastric parietal cells. It further activates adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) levels. This results in reduced secretion of gastric acid and increased production of protective mucus in the stomach. 

Pharmacokinetics: 

Absorption 

diclofenac can be administered orally, topically, or intravenously. Oral diclofenac is well absorbed from the gastrointestinal tract, but its absorption may be delayed if taken with food. diclofenac undergoes extensive first-pass metabolism in the liver, resulting in a lower systemic bioavailability than intravenous administration. 

misoprostol is well absorbed after oral administration. It undergoes rapid and extensive metabolism in the liver, resulting in a low systemic bioavailability due to first-pass metabolism. The absolute bioavailability is increased when administered rectally. 

Distribution 

diclofenac is highly protein-bound, primarily to albumin. It has a moderate volume of distribution and can penetrate synovial fluid, where it exerts anti-inflammatory effects. misoprostol is extensively bound to plasma proteins, primarily albumin. It has a small volume of distribution.  

Metabolism 

diclofenac is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, particularly CYP2C9 and CYP3A4. The significant metabolites include 4-hydroxy diclofenac, 5-hydroxy diclofenac, and glucuronide/sulfate conjugates. The metabolites are mainly eliminated in the urine. 

misoprostol is metabolized in the liver via oxidation and fatty acid side-chain oxidation. The major metabolite is misoprostol acid, which exhibits similar pharmacological activity to the parent compound. misoprostol acid is further metabolized to inactive metabolites. 

Elimination and Excretion 

The elimination half-life of diclofenac is approximately 2 to 3 hours. The elimination half-life of misoprostol is approximately 20 to 40 minutes. The drugs and their metabolites are majorly excreted in the urine, with a smaller portion eliminated in the feces. 

Adminstartion

Administration: 

diclofenac/misoprostol combination medication is typically available in tablet form for oral administration. The specific dosing instructions and regimen may vary depending on the product. Follow the instructions provided by your healthcare professional and the medication’s prescribing information. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: diclofenac/misoprostol 

Pronounced: dye-KLOE-fen-ak-and-mye-so-PROST-ole 

Why do we use diclofenac/misoprostol?  

diclofenac/misoprostol combination medication is primarily used in treating signs and symptoms of rheumatoid arthritis and osteoarthritis in patients at high risk for developing NSAID-induced gastric ulcers.