Diclofenac + Omeprazole

Usage

• Diclofenac + Omeprazole is prescribed for the symptomatic treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis in patients at risk of developing NSAID-associated gastric and/or duodenal ulcers. It is also used for other painful inflammatory conditions when the patient is at risk of ulcer development.
• Pharmacological Classification: Non-steroidal anti-inflammatory drug (NSAID) + Proton Pump Inhibitor (PPI).
• Mechanism of Action: Diclofenac inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and thus inflammation and pain. Omeprazole inhibits the proton pump in the stomach, reducing gastric acid production, which protects against NSAID-induced ulcers.

Alternate Names

• Dicloduo Combi
• Brand Names: Yosprala (aspirin/omeprazole), Arthrotec (diclofenac/misoprostol), Vimovo (naproxen/esomeprazole magnesium). There is no specific brand name available for a Diclofenac + Omeprazole combination as of now. However, many pharmaceutical companies produce generic versions.

How It Works

• Pharmacodynamics: Diclofenac exerts analgesic, anti-inflammatory, and antipyretic effects by inhibiting COX-1 and COX-2 enzymes. Omeprazole suppresses gastric acid secretion by inhibiting H+/K+-ATPase in gastric parietal cells.
• Pharmacokinetics: Diclofenac is well-absorbed orally, metabolized in the liver, and excreted primarily through the kidneys. Omeprazole is also well-absorbed orally, extensively metabolized by CYP2C19 and CYP3A4 in the liver, and excreted mainly in urine.
• Mode of Action: Diclofenac competes with arachidonic acid for the active site of COX enzymes, reducing the formation of prostaglandin precursors. Omeprazole binds irreversibly to the proton pump, inhibiting acid secretion.
• Elimination Pathways: Primarily renal excretion for both Diclofenac and Omeprazole, after hepatic metabolism involving various CYP enzymes for Omeprazole.

Dosage

Standard Dosage

Adults:

• One capsule containing 75 mg Diclofenac and 20 mg Omeprazole daily. Administer orally, preferably with food, and swallow the capsule whole.

Children:

• Not suitable for children.

Special Cases:

• Elderly Patients: Monitor closely for adverse effects and consider initiating therapy at the lowest dose due to increased risk of serious consequences.
• Patients with Renal Impairment: Mild to moderate: Caution advised, close monitoring of renal function. Severe: Contraindicated.
• Patients with Hepatic Dysfunction: Mild to moderate: Caution advised, close monitoring of liver function. Severe: Contraindicated.
• Patients with Comorbid Conditions: Close monitoring required, especially in patients with a history of hypertension, cardiovascular disease, diabetes or those receiving concomitant medications affecting renal function.

Clinical Use Cases

• Dosage recommendations for the listed clinical scenarios are not specific to the Diclofenac + Omeprazole combination. As this is primarily indicated for chronic inflammatory conditions, its use in acute settings like intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations is not routinely recommended. Pain management in these situations would require a different approach.

Dosage Adjustments

• Adjust based on patient-specific factors such as renal/hepatic dysfunction and comorbid conditions. Start at the lowest dose, and if symptoms are not controlled, consider alternative treatment strategies instead of increasing the dose.

Side Effects

Common Side Effects

• Headache, diarrhea, stomach pain, constipation, flatulence, nausea, vomiting, benign polyps in the stomach, dizziness, tingling sensations, sleep disturbances, swelling of extremities.

Rare but Serious Side Effects

• Blood disorders (reduced white cells or platelets), severe allergic reactions (swelling of lips, tongue, throat, fever, wheezing), low sodium levels, agitation, confusion, depression, vision changes, taste changes, gastrointestinal bleeding or perforation, hypersensitivity reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, hepatotoxicity and nephrotoxicity.

Long-Term Effects

• Increased risk of fractures (hip, wrist, spine), especially with prolonged use of omeprazole (over a year). Small increased risk of heart attack and stroke with prolonged use, especially at high doses.

Adverse Drug Reactions (ADR)

• Severe allergic reactions, gastrointestinal bleeding, acute kidney injury, hepatotoxicity, bone marrow suppression, cardiovascular thrombotic events (heart attack, stroke), Stevens-Johnson syndrome, toxic epidermal necrolysis, lupus-like syndrome.

Contraindications

• Hypersensitivity to diclofenac, omeprazole, or other NSAIDs/PPIs. Active gastrointestinal bleeding or ulceration. Severe heart, liver, or kidney failure. Last trimester of pregnancy. Porphyria. History of asthma, urticaria, or other allergic-type reactions after NSAID use. Coronary artery bypass graft surgery.

Drug Interactions

• NSAIDs (ibuprofen), anticoagulants (warfarin), antifungals (ketoconazole), methotrexate, lithium, SSRIs, digoxin, cilostazol, phenytoin, rifampicin, clopidogrel, other CYP2C19 and CYP3A4 inhibitors/inducers. Alcohol should be avoided, as it can increase the risk of GI bleeding.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (first and second trimester) / D (third trimester).
• Fetal Risks: Premature closure of ductus arteriosus, oligohydramnios, prolonged labor, increased bleeding tendency in the newborn, potential developmental concerns.
• Breastfeeding: Small amounts of diclofenac may pass into breast milk. Omeprazole’s presence in breast milk is uncertain, but potential for infant exposure exists. While both are considered compatible with breastfeeding, alternatives should be considered if the infant exhibits any adverse effects.

Drug Profile Summary

• Mechanism of Action: Diclofenac: COX inhibitor, reducing inflammation and pain. Omeprazole: Proton pump inhibitor, reducing gastric acid.
• Side Effects: Common: GI upset, headache. Serious: GI bleeding, cardiovascular events.
• Contraindications: Hypersensitivity, GI bleeding, severe organ dysfunction, pregnancy (third trimester).
• Drug Interactions: NSAIDs, anticoagulants, antifungals, lithium, SSRIs.
• Pregnancy & Breastfeeding: Use with caution, especially during the third trimester and while breastfeeding. Monitor the infant.
• Dosage: Adults: One capsule (75mg/20mg) daily.
• Monitoring Parameters: Renal and hepatic function, blood pressure, complete blood count, signs of GI bleeding.

Popular Combinations

This section is not applicable, as this medication itself is a popular combination used specifically to mitigate the risk of NSAID-induced ulcers. It is not commonly combined with other medications.

Precautions

• General Precautions: Evaluate for allergies, renal/hepatic dysfunction, cardiovascular disease. Monitor for GI bleeding, renal function, and blood pressure. Advise against concomitant use of other NSAIDs.
• Specific Populations: Pregnant women: Avoid during the third trimester. Breastfeeding mothers: Monitor the infant closely. Children: Not suitable. Elderly: Start with the lowest effective dose. Monitor closely for adverse reactions.
• Lifestyle Considerations: Avoid alcohol. Smoking may increase the risk of cardiovascular events.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Diclofenac + Omeprazole?

A: One capsule (75 mg Diclofenac + 20 mg Omeprazole) once daily for adults. Not for use in children.

Q2: Can Diclofenac + Omeprazole be used during pregnancy?

A: It is contraindicated during the third trimester. Use cautiously during the first and second trimesters only if clearly necessary, at the lowest effective dose and for the shortest possible duration.

Q3: How should Diclofenac + Omeprazole be administered?

A: Orally, swallow whole with a glass of water, preferably with food.

Q4: What are the most serious side effects of this medication?

A: Gastrointestinal bleeding or ulceration, cardiovascular thrombotic events (heart attack, stroke), severe allergic reactions, significant liver or kidney impairment.

Q5: Can patients with a history of peptic ulcer disease take this combination?

A: Patients with an active peptic ulcer or a history of recurrent ulcers/hemorrhage should not take this medication.

Q6: What are the key drug interactions to be aware of?

A: Interactions can occur with other NSAIDs, anticoagulants, antifungals, lithium, methotrexate, and SSRIs.

Q7: Can I prescribe Diclofenac + Omeprazole with other NSAIDs like Ibuprofen?

A: Concomitant use of other NSAIDs should be avoided due to increased risk of adverse effects.

Q8: What is the role of Omeprazole in this combination?

A: Omeprazole reduces the risk of NSAID-induced gastric and duodenal ulcers.

Q9: What patient education should be provided regarding this medication?

A: Explain potential side effects, drug interactions, and contraindications. Advise patient to report any unusual symptoms immediately, especially GI issues. Instruct patients to take as prescribed and not to exceed the recommended dosage. Discuss lifestyle modifications.

Q10: Can this medication be used long term?

A: Long-term use should be under regular medical supervision, with careful monitoring for adverse effects, especially related to GI and cardiovascular systems and for prolonged PPI usage, bone density. Periodic reassessment of treatment benefits and risks is essential.