Usage
Diclofenac + Tranexamic Acid is primarily prescribed for the treatment of heavy menstrual bleeding (menorrhagia) accompanied by menstrual pain (dysmenorrhea). It combines the analgesic and anti-inflammatory properties of diclofenac with the antifibrinolytic action of tranexamic acid.
Pharmacological Classification:
- Diclofenac: Non-Steroidal Anti-Inflammatory Drug (NSAID)
- Tranexamic Acid: Antifibrinolytic
Mechanism of Action: Diclofenac inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, which contributes to pain and inflammation relief. Tranexamic acid inhibits plasminogen activation, thereby preventing the breakdown of fibrin clots and reducing bleeding.
Alternate Names
There is no internationally recognized non-proprietary name for the combination. However, the individual components are recognized as diclofenac and tranexamic acid globally.
Brand Names: Pause D is a recognized brand name for this combination. Other brand names may exist regionally.
How It Works
Pharmacodynamics: Diclofenac exerts analgesic and anti-inflammatory effects by inhibiting prostaglandin synthesis. Tranexamic acid reduces bleeding by inhibiting plasminogen activation and preventing fibrinolysis.
Pharmacokinetics:
- Diclofenac: Well-absorbed orally. Metabolized primarily in the liver by CYP2C9 (major route) and by glucuronidation (UGT2B7). Eliminated renally and in bile.
- Tranexamic Acid: Well-absorbed orally. Minimal metabolism. Excreted primarily unchanged in the urine via glomerular filtration.
Mode of Action:
- Diclofenac: Reversibly inhibits COX-1 and COX-2 enzymes, leading to decreased formation of prostaglandin precursors.
- Tranexamic Acid: Competitively inhibits the binding of plasminogen and plasmin to fibrin, preventing fibrinolysis.
Receptor binding, enzyme inhibition, or neurotransmitter modulation:
- Diclofenac: COX-1 and COX-2 enzyme inhibition.
- Tranexamic Acid: Plasminogen and plasmin inhibition.
Elimination pathways:
- Diclofenac: Renal and hepatic excretion.
- Tranexamic Acid: Primarily renal excretion.
Dosage
Standard Dosage
Adults: The usual dose is Diclofenac 50 mg + Tranexamic Acid 500 mg. A common regimen is to take one tablet three times a day, usually starting at the onset of menstruation and continuing for up to five days. An initial dose of diclofenac 100 mg followed by 50 mg doses may provide better pain relief for some individuals. The maximum daily dose of diclofenac should not exceed 150 mg.
Children: The combination is not typically recommended for use in children. Individual dosing of tranexamic acid in children is weight-based (e.g., 10 mg/kg IV bolus).
Special Cases:
- Elderly Patients: Close monitoring is advised. Renal function should be assessed, and dosage adjustments may be necessary.
- Patients with Renal Impairment: Dose reduction is essential. See Dosage Adjustments section below.
- Patients with Hepatic Dysfunction: Close monitoring is necessary, and dose adjustment of diclofenac may be required.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, hypertension, or diabetes due to increased risk of thromboembolic events and cardiovascular complications with both diclofenac and tranexamic acid.
Clinical Use Cases
The combination of Diclofenac and Tranexamic acid is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Tranexamic acid alone is used in some of these situations. Diclofenac, being an NSAID, can increase the risk of bleeding, and therefore would be contraindicated in these scenarios.
Dosage Adjustments
- Renal Impairment (Tranexamic Acid): Dose reduction is necessary in patients with renal impairment. Some suggested adjustments are 1300 mg twice daily if serum creatinine is between 1.4 and 2.8 mg/dL, 1300 mg once daily if it’s between 2.8 and 5.7 mg/dL, and 650 mg once daily if it’s greater than 5.7 mg/dL. Each regimen may be administered for up to 5 days during menstruation.
Side Effects
Common Side Effects
- Nausea
- Vomiting
- Diarrhea
- Dyspepsia
- Abdominal pain
- Headache
- Fatigue
- Nasal congestion
Rare but Serious Side Effects
- Thromboembolic events (deep vein thrombosis, pulmonary embolism)
- Seizures (especially with high doses of tranexamic acid)
- Visual disturbances
- Allergic reactions (including anaphylaxis)
- Myocardial infarction
- Stroke
Long-Term Effects
- Gastrointestinal bleeding or ulceration (with diclofenac)
- Renal impairment (with diclofenac)
- Cardiovascular complications (with diclofenac)
Adverse Drug Reactions (ADR)
- Angioedema
- Stevens-Johnson syndrome
Contraindications
- Hypersensitivity to diclofenac, tranexamic acid, or other NSAIDs.
- Active venous or arterial thromboembolic disease.
- Severe renal impairment.
- History of seizures.
- Pregnancy (especially the third trimester).
- Active or recent gastrointestinal bleeding or ulceration.
- Severe hepatic impairment.
- Uncorrected hypovolemia or dehydration.
- Concomitant use with other NSAIDs.
Drug Interactions
- Anticoagulants/Antiplatelets: Increased risk of bleeding.
- Other NSAIDs: Increased risk of gastrointestinal and renal adverse effects.
- Hormonal contraceptives: Increased risk of thromboembolic events.
- Antihypertensives: May decrease the effectiveness of antihypertensive medications.
- Alcohol: Increased risk of gastrointestinal bleeding with diclofenac.
Pregnancy and Breastfeeding
Diclofenac is contraindicated during the third trimester of pregnancy. Tranexamic acid is generally avoided during pregnancy due to limited safety data, although it is classified as FDA pregnancy category B for IV/parenteral/oral use. Diclofenac is considered compatible with breastfeeding in limited amounts. Very small amounts of tranexamic acid pass into breast milk. Neonatal side effects are unlikely, but follow-up monitoring is recommended.
Drug Profile Summary
- Mechanism of Action: Diclofenac: COX inhibitor, Tranexamic Acid: Antifibrinolytic.
- Side Effects: Nausea, vomiting, gastrointestinal issues, thromboembolic events, visual disturbances.
- Contraindications: Hypersensitivity, thromboembolic disease, pregnancy, severe renal/hepatic impairment.
- Drug Interactions: Anticoagulants, other NSAIDs, hormonal contraceptives.
- Pregnancy & Breastfeeding: Diclofenac: avoid in third trimester, compatible with breastfeeding. Tranexamic Acid: use with caution, monitor infant.
- Dosage: Adults: Diclofenac 50 mg + Tranexamic Acid 500 mg TID for up to 5 days during menstruation. Renal adjustments needed.
- Monitoring Parameters: Renal function, liver function, signs of bleeding, blood pressure.
Popular Combinations
This combination itself is commonly used. However, using it with mefenamic acid may be considered in specific cases where further pain management is required.
Precautions
- Renal function should be evaluated before and during treatment, especially in the elderly and those with renal impairment.
- Monitor for signs of thromboembolic events and visual disturbances.
- Advise patients about potential gastrointestinal side effects and precautions.
- Use cautiously in patients with a history of cardiovascular disease.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diclofenac + Tranexamic Acid for heavy menstrual bleeding?
A: The usual dose is Diclofenac 50 mg + Tranexamic Acid 500 mg three times a day, beginning with the onset of menses and continuing for up to 5 days.
Q2: What are the major contraindications to this combination?
A: Thromboembolic disease, hypersensitivity to components, severe renal impairment, pregnancy (third trimester).
Q3: How does tranexamic acid work to control bleeding?
A: It inhibits plasminogen activation, preventing fibrinolysis and promoting clot stability.
Q4: What are the potential drug interactions with Diclofenac + Tranexamic Acid?
A: Anticoagulants, other NSAIDs, and hormonal contraceptives can interact significantly.
Q5: Can this combination be used in patients with liver disease?
A: Use with caution as diclofenac is metabolized in the liver. Dose adjustments might be needed. Close monitoring is necessary.
Q6: Are there any visual side effects associated with this drug?
A: Tranexamic acid can cause visual disturbances, including changes in color vision. If any visual changes occur, discontinue the medicine and consult an ophthalmologist.
Q7: What are the main side effects patients should be aware of?
A: Nausea, vomiting, diarrhea, headache, fatigue, and abdominal discomfort. More seriously, thromboembolic events and visual changes.
Q8: Can this drug be used during pregnancy?
A: Diclofenac is contraindicated in the third trimester. Tranexamic acid should be avoided in pregnancy unless benefits outweigh potential risks.
Q9: Can this medication be used with other painkillers like ibuprofen or aspirin?
A: Concomitant use with other NSAIDs is generally avoided due to the increased risk of adverse effects.
Q10: How should the dosage be adjusted in patients with kidney problems?
A: Dosage reduction of tranexamic acid is crucial. Specific adjustments are based on creatinine clearance or serum creatinine levels. Consult dosage guidelines or a nephrologist.
