Drotaverine + Ethamsylate + Tranexamic Acid

Usage

This combination medication is primarily prescribed for the management of menorrhagia (heavy menstrual bleeding) and associated pain. It combines the antispasmodic action of drotaverine with the hemostatic effects of ethamsylate and tranexamic acid.

• Pharmacological Classification: This drug combines medications from three classifications:

  • Drotaverine: Antispasmodic
  • Ethamsylate: Hemostatic
  • Tranexamic acid: Antifibrinolytic

• Mechanism of Action: Drotaverine relaxes smooth muscles in the uterus, alleviating pain from menstrual cramps (dysmenorrhea). Ethamsylate enhances platelet adhesion and reduces capillary bleeding. Tranexamic acid inhibits fibrinolysis, preventing the breakdown of blood clots, thereby further reducing bleeding.

Alternate Names

While no specific international non-proprietary name exists for this combination product, it may be referred to as a “Drotaverine, Ethamsylate, and Tranexamic acid combination.”

• Brand Names: Ethamax TD, Track D are two examples of the brand names used for this combination. Other brand names might exist.

How It Works

• Pharmacodynamics: Drotaverine, a phosphodiesterase IV inhibitor, relaxes uterine smooth muscles. Ethamsylate increases capillary resistance and promotes platelet adhesion. Tranexamic acid, an antifibrinolytic, reversibly blocks lysine binding sites on plasminogen, preventing its activation to plasmin, and thereby inhibiting fibrinolysis and stabilizing clots.

• Pharmacokinetics:

  • Drotaverine: Well absorbed orally, undergoes hepatic metabolism, primarily by CYP2D6.
  • Ethamsylate: Partially metabolized, primarily in the liver.
  • Tranexamic Acid: Primarily excreted unchanged in the urine with a plasma half-life of approximately 3 hours.

• Mode of Action:

  • Drotaverine: Inhibits phosphodiesterase enzyme, increasing intracellular cAMP, leading to smooth muscle relaxation.
  • Ethamsylate: Works by increasing capillary endothelial resistance and improving platelet aggregation.
  • Tranexamic Acid: Reversibly binds to lysine receptor sites on plasminogen, inhibiting plasmin formation and thus preventing fibrinolysis.

• Elimination Pathways:

  • Drotaverine: Primarily hepatic metabolism.
  • Ethamsylate: Partially hepatic metabolism with renal excretion.
  • Tranexamic Acid: Predominantly renal excretion.

Dosage

Standard Dosage

Adults: One tablet (containing 80mg Drotaverine, 250mg Ethamsylate, and 250mg Tranexamic acid) two to three times daily, typically starting on the first day of menstruation and continuing for up to five days.

Children: This combination is generally not recommended for use in children. The safety and effectiveness in pediatric populations have not been well established.

Special Cases:

• Elderly Patients: Dose adjustments may be necessary depending on renal function.
• Patients with Renal Impairment: Dose reduction is recommended, especially for tranexamic acid.
• Patients with Hepatic Dysfunction: Caution is advised, although specific dosage adjustments may not be routinely necessary.
• Patients with Comorbid Conditions: Patients with a history of thromboembolic events should use this combination with caution.

Clinical Use Cases

The primary clinical use case is the management of menorrhagia and dysmenorrhea. The use of this drug in other settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not established.

Dosage Adjustments

Dosage modifications should be considered for patients with renal or hepatic impairment and any other comorbidity.

Side Effects

Common Side Effects

Headache, nausea, vomiting, dizziness, gastrointestinal discomfort (including abdominal pain, diarrhea), dryness in mouth, sinus inflammation, sinus pain, tiredness, musculoskeletal pain, rash, and anemia.

Rare but Serious Side Effects

Thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke). Vision changes (requiring immediate ophthalmological evaluation). Allergic reactions.

Long-Term Effects

The long-term effects of continuous or repeated use of this combination have not been fully evaluated.

Adverse Drug Reactions (ADR)

Anaphylaxis, angioedema, thrombotic complications.

Contraindications

• Hypersensitivity to any of the components.
• Active thromboembolic disease.
• Severe renal impairment.
• Subarachnoid hemorrhage.
• Concomitant use of combined hormonal contraceptives.
• History of retinal artery or vein occlusion.
• Defective color vision

Drug Interactions

• Combined hormonal contraceptives (increased risk of thrombosis with tranexamic acid).
• Anticoagulants (may enhance the anticoagulant effect).
• Factor IX complex concentrates or anti-inhibitor coagulant concentrates (increased risk of thrombosis).
• Alcohol.

Pregnancy and Breastfeeding

The safety of this combination in pregnancy and breastfeeding has not been fully established. Use with caution only if potential benefits clearly outweigh the risks. Tranexamic acid is excreted in breast milk; monitor the infant for potential adverse effects.

Drug Profile Summary

• Mechanism of Action: Antispasmodic, hemostatic, and antifibrinolytic.
• Side Effects: Headache, nausea, vomiting, dizziness, gastrointestinal discomfort, thrombosis (rare), dryness in mouth, sinus inflammation, sinus pain, tiredness, musculoskeletal pain, rash, and anemia.
• Contraindications: Hypersensitivity, active thromboembolic disease, severe renal impairment, subarachnoid hemorrhage.
• Drug Interactions: Combined hormonal contraceptives, anticoagulants.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
• Dosage: One tablet two to three times daily, starting on the first day of menstruation for up to five days.
• Monitoring Parameters: Menstrual bleeding, signs of thrombosis, renal function, vision changes.

Popular Combinations

This combination itself represents a commonly used formulation for managing menorrhagia. However, it can potentially be combined with NSAIDs for added analgesic effects. Careful monitoring is necessary.

Precautions

• Assess for allergies, renal/hepatic function, and history of thromboembolic events.
• Avoid alcohol during treatment.
• Counsel on the risk of thrombosis.
• Regular monitoring of blood pressure and eye check-up.
• Caution in patients with a history of low blood pressure.
• Avoid driving if dizziness occurs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Drotaverine + Ethamsylate + Tranexamic Acid?

A: The standard adult dosage is one tablet (80mg Drotaverine, 250mg Ethamsylate, and 250mg Tranexamic acid) two or three times daily, commencing on the first day of menses and continuing for up to five days. Dosage adjustments may be necessary based on renal function and other comorbidities. Pediatric use is generally not recommended.

Q2: What are the primary side effects of this combination?

A: Common side effects include headache, nausea, dizziness, gastrointestinal discomfort, dryness in mouth, sinus inflammation, sinus pain, tiredness, musculoskeletal pain, rash, and anemia. Rare but serious side effects may include thromboembolic events and vision changes.

Q3: Is this medication safe during pregnancy or breastfeeding?

A: The safety during pregnancy and breastfeeding is not definitively established. Use only if benefits outweigh risks. Tranexamic acid does excrete into breast milk, so monitor the infant for any adverse events.

Q4: How does Drotaverine + Ethamsylate + Tranexamic Acid work to reduce heavy menstrual bleeding?

A: Drotaverine relaxes the uterine muscles, reducing cramping pain. Ethamsylate enhances platelet function and capillary resistance, while Tranexamic acid inhibits the breakdown of blood clots, all contributing to reduced bleeding.

Q5: Are there any contraindications to the use of this medication?

A: Yes. Contraindications include hypersensitivity to any component, active thromboembolic disease, severe renal impairment, subarachnoid hemorrhage, and concomitant use of combined hormonal contraceptives.

Q6: What are the key drug interactions to consider?

A: Significant interactions may occur with combined hormonal contraceptives (increased thrombosis risk) and anticoagulants (enhanced anticoagulant effect).

Q7: What monitoring parameters are important while a patient is on this medication?

A: Monitor menstrual bleeding, signs and symptoms of thrombosis (leg pain, swelling, shortness of breath), renal function, and vision changes.

Q8: Can this medication be used in patients with liver disease?

A: While the combination is generally considered safe in patients with liver disease, caution is advised. Consult a specialist for personalized advice.

Q9: Can this medication be used in patients with kidney problems?

A: Use with caution in patients with kidney problems. Dose adjustment of tranexamic acid component may be necessary based on the degree of renal impairment.

Q10: Can the missed dose be doubled the next time?

A: No, it is recommended to take the missed dose as soon as it is remembered. Do not double the dose. If it’s almost time for the next scheduled dose, skip the missed one.