Dicynone 250 & 500 (Etamsylate) – Haemostatic for Capillary Bleeding, Menorrhagia & Surgical Haemostasis Guide

DICYNONE® / DICYNONE® 500

1. Disclaimer

This monograph is intended for educational and informational purposes only and does not replace consultation with a qualified physician, pharmacist, or the officially approved product leaflet. Dosing decisions, indications, and clinical management must always be individualized and made by a licensed healthcare professional based on the patient's condition.

We do not guarantee the accuracy, currency or completeness of information regarding medications or medical products, and official sources should be verified before making any decisions. Readers are responsible for independently verifying the information before relying on it.

Product availability, pack sizes, local manufacturer/licensee, and regulatory status vary from country to country and may change over time.

2. Summary

Dicynone (etamsylate) is a synthetic, non-hormonal systemic haemostatic and angioprotective agent. It acts at the first step of haemostasis by enhancing platelet adhesiveness and restoring capillary resistance, thereby reducing bleeding time and blood loss without vasoconstriction and without altering plasma coagulation factors or fibrinolysis. It is used in surgery, internal medicine, gynaecology, and neonatology (prevention of periventricular haemorrhage in premature infants) and is available as 250 mg/2 mL ampoules, 250 mg tablets, and 500 mg tablets.

3. Brand Name

Dicynone® (also marketed internationally as Dicynon, Dicynene, Cyclonamine). In the Egyptian market, common presentations include Dicynone 250 mg tablets, Dicynone 250 mg/2 mL ampoules, and Dicynone 500 mg tablets.

4. Category

• Pharmacological class: Systemic haemostatic / antihaemorrhagic and angioprotective agent.
• ATC code: B02BX01 (Other systemic haemostatics).

5. Active Ingredient

Etamsylate (INN) — also spelled Ethamsylate (USAN/BAN).

• Chemical name: diethylammonium 2,5-dihydroxybenzenesulfonate.
• Molecular formula: C₁₀H₁₇NO₅S; molecular weight ≈ 263 g/mol.
• CAS Registry No.: 2624-44-4.

Note: some older leaflets describe the salt as "1,4-dihydroxybenzenesulfonate"; the internationally recognized chemistry per pharmacopoeial and INN sources is the 2,5-dihydroxy isomer.

6. Pharmaceutical Form & Strength

• Ampoules for injection: 250 mg / 2 mL (IV or IM), contains sodium metabisulfite (E 223) 0.8 mg as antioxidant.
• Tablets: 250 mg etamsylate.
• Dicynone 500 tablets: 500 mg etamsylate, contains sodium sulfite (E 221) as antioxidant.

7. Manufacturer & Marketing Authorization Holder

• Originator / global licensor: OM Pharma, Meyrin-Geneva, Switzerland (a Vifor/OM Pharma group product).
• Egyptian market (local manufacture / co-marketing under licence from OM Pharma – Switzerland):
  • Dicynone 250 mg tablets — Memphis Co. for Pharmaceutical & Chemical Industries, under licence from OM Pharma.
  • Dicynone 250 mg/2 mL ampoules — Minapharm Pharmaceuticals, under licence from OM Pharma – Switzerland.
  • Dicynone 500 mg tablets — Minapharm Pharmaceuticals, under licence from OM Pharma.

8. Mechanism of Action

Etamsylate acts on the first stage of haemostasis (endothelium–platelet interaction). It:

• Improves platelet adhesiveness and aggregability.
• Restores impaired capillary resistance and reduces capillary permeability, likely through interaction with the endothelial basement membrane and inhibition of prostacyclin (PGI₂) synthesis, which favours platelet plug formation at the bleeding site.
• Shortens bleeding time and reduces the volume of blood loss.

Importantly, etamsylate has no vasoconstrictor effect, does not influence fibrinolysis, and does not modify plasma coagulation factors — so it does not predispose to hypercoagulability or systemic thrombosis at recommended doses.

9. Spectrum of Activity

Etamsylate is not an antimicrobial; the term here refers to the spectrum of bleeding disorders in which it is used. It is effective against capillary-type bleeding of diverse origins — surgical oozing from richly vascularized tissues, gynaecological bleeding (menorrhagia, metrorrhagia, IUD-related bleeding), ENT bleeding (epistaxis, gingivorrhagia), gastrointestinal capillary bleeding (haematemesis, melaena), urinary tract (haematuria), and neonatal periventricular/intraventricular haemorrhage of prematurity. It is not effective for bleeding due to major coagulation-factor deficiencies (e.g., haemophilia) or anticoagulant overdose, which require specific therapy.

10. Pharmacokinetics

• Intravenous route: After a 500 mg IV dose, peak plasma concentration (~50 µg/mL) is reached within about 10 minutes. Plasma half-life ≈ 1.9 hours. About 85% of the administered dose is eliminated in the urine within the first 24 hours, largely unchanged.
• Oral route: Absorbed through the gastrointestinal tract. Peak plasma level (~15 µg/mL) reached ~4 hours after a 500 mg oral dose. Plasma half-life ≈ 3.7 hours; approximately 72% of the dose is excreted unchanged in the urine within 24 hours.
• Distribution: Etamsylate crosses the placental barrier; maternal and cord-blood concentrations are similar. Excretion into breast milk has not been fully characterized.
• Metabolism: The molecule is largely excreted unchanged; extensive hepatic metabolism is not a major elimination pathway.

11. Indications

• Surgery: Prevention and treatment of pre-, intra-, and post-operative capillary oozing in delicate operations and highly vascularized tissues — ENT, gynaecology, obstetrics, urology, odontostomatology, ophthalmology, plastic and reconstructive surgery.
• Internal medicine: Prevention and treatment of capillary haemorrhages of various origins and sites — haematuria, haematemesis, melaena, metrorrhagia, primary or IUD-associated menorrhagia, epistaxis, gingivorrhagia.
• Paediatrics/Neonatology: Prevention of periventricular/intraventricular haemorrhage in premature neonates.

12. Administration

Dicynone 250 mg (ampoule and tablet):

• Adults – pre-surgical: 1–2 ampoules IV or IM, one hour before surgery.
• Adults – intra-operative: 1–2 ampoules IV; repeat if necessary.
• Adults – post-surgical: 1–2 ampoules or 1–2 tablets every 4–6 hours as long as the bleeding risk persists.
• Adult emergency use: 1–2 ampoules IV or IM every 4–6 hours according to severity.
• Local (topical) use: Soak a sterile swab with the contents of one ampoule and apply to the bleeding area, or place in the socket after dental extraction; may be combined with oral or parenteral therapy.
• Children (>1 month): Half the adult dose.
• Neonates (prevention of periventricular haemorrhage): 10 mg/kg body weight IM (0.1 mL = 12.5 mg) within 2 hours of birth, then every 6 hours for 4 days.

Dicynone 500 mg tablets (adults):

• Post-surgical: 1 tablet every 4–6 hours while bleeding risk persists.
• Internal medicine: Usually 2–3 tablets daily; duration guided by clinical response.
• Gynaecology – menorrhagia/metrorrhagia: 3 tablets daily for 10 days, starting 5 days before the expected onset of menstruation.
• Children: Half the adult dose.

13. Method of Preparation

• Tablets: Ready to use; swallow whole with a glass of water, preferably with or after meals to minimize gastric upset.
• Ampoules: The 250 mg/2 mL solution is ready for injection.
  • Administer IV slowly (over about 1–2 minutes) or by deep IM injection.
  • The solution may be added to compatible IV infusion fluids (e.g., 0.9% sodium chloride, 5% dextrose) for slow infusion when clinically appropriate; use immediately after dilution and do not mix with sodium bicarbonate solutions or with dextran in the same syringe.
  • When a dextran infusion is required, etamsylate should be administered first, before the dextran.
  • For topical/local haemostasis, the ampoule content may be applied on a sterile swab to the bleeding surface or into a tooth socket after extraction.
  • Discard the ampoule if the solution appears coloured.

14. Contraindications

• Known hypersensitivity to etamsylate or to any excipient of the formulation (notably sodium metabisulfite/sulfite in the ampoules and 500 mg tablets, which can rarely trigger severe hypersensitivity/asthma reactions in susceptible individuals).
• Acute porphyria (etamsylate has been reported to precipitate acute attacks in porphyric patients).
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency – use with caution/avoid, due to risk of haemolysis.

15. Warnings & Precautions

• A test dose is recommended in patients with a history of allergic diathesis, given the sulfite content of the injectable form and 500 mg tablets.
• Transient falls in systolic blood pressure have occasionally been reported after rapid IV administration — inject slowly.
• Use with caution in patients with a history of thromboembolic events; while etamsylate does not modify plasma coagulation factors, clinical judgment is advised in such patients.
• Rule out major surgical or coagulopathic causes of bleeding before attributing failure of therapy to inadequate dosing; etamsylate does not substitute for surgical haemostasis or specific factor replacement.
• Not intended for use during the first trimester of pregnancy (see Special Populations).
• Injectable solution: protect ampoules from light; discard if the solution is discoloured.

16. Drug Interactions

• Dextran infusions: Administer etamsylate before dextran; giving dextran first can reduce the haemostatic activity of etamsylate.
• Anticoagulants (heparin, warfarin, DOACs): Etamsylate may be co-administered when clinically justified; it does not modify plasma coagulation factors, but clinical monitoring of bleeding/coagulation status is prudent.
• Thiamine (vitamin B1): Etamsylate is reported to inactivate thiamine; do not mix in the same syringe or infusion line.
• Sodium bicarbonate and alkaline solutions: Physically/chemically incompatible in the same syringe.
• No clinically significant CYP-mediated interactions are described, as the drug is mainly excreted unchanged in urine.

17. Side Effects

Etamsylate is generally well tolerated. Reported adverse effects include:

• Gastrointestinal: Nausea, epigastric discomfort, vomiting, diarrhoea.
• Nervous system: Headache, dizziness, transient asthenia.
• Skin: Rash, pruritus, erythema.
• Cardiovascular: Transient hypotension, rarely with rapid IV injection.
• Haematological/immunological (rare): Hypersensitivity reactions (including bronchospasm/anaphylactoid reactions attributable to sulfite excipients); very rarely agranulocytosis and thrombocytopenia have been reported in post-marketing surveillance.
• Others: Fever and back/joint pain reported rarely.

Serological (immune) side effects are not characteristic of the molecule itself.

18. Use in Special Populations

• Pregnancy: Not recommended during the first trimester. In the second and third trimesters, use only if the potential benefit outweighs the potential risk and under medical supervision. Etamsylate crosses the placenta.
• Lactation: Data on excretion into human milk are limited; use only if clearly indicated and under medical supervision.
• Paediatric use: Dose is half the adult dose in children >1 month; specific neonatal regimen (10 mg/kg IM every 6 hours for 4 days) is used to prevent periventricular haemorrhage in premature infants.
• Elderly: No specific dose adjustment; use standard adult dosing with attention to renal function and comorbidities.
• Renal impairment: As the drug is largely excreted unchanged in urine, caution and dose review are advisable in severe renal impairment, though formal dose-adjustment recommendations are not established.
• Hepatic impairment: No specific dose adjustment is generally required; use with clinical caution.

19. Storage Conditions

• Store below 25 °C in the original packaging.
• Protect the ampoules from light.
• Do not use the ampoules if the solution has become discoloured.
• Keep out of the sight and reach of children.
• Do not use after the expiration date (EXP) printed on the pack.

20. Additional Sections

Overdose

Overdose: Experience with etamsylate overdose is limited. Management is symptomatic and supportive; there is no specific antidote. Monitor blood pressure and general status.

Effect on laboratory tests

Effect on laboratory tests: Etamsylate may interfere with some laboratory assays (e.g., certain creatinine measurements based on the Jaffé reaction), potentially yielding falsely low values while the drug is in the circulation.

Effects on ability to drive/use machines

Effects on ability to drive/use machines: No relevant effect at usual doses; caution if dizziness occurs.

Excipient warnings

Excipient warnings: Sulfite antioxidants (E 221 sodium sulfite / E 223 sodium metabisulfite) may cause allergic-type reactions, including anaphylactic symptoms and bronchospasm in susceptible patients, particularly those with a history of asthma.

21. Frequently Asked Questions (FAQ)

Q1. Is Dicynone a hormone?

No. Etamsylate is a non-hormonal synthetic haemostatic agent; it can be used for heavy menstrual bleeding without hormonal effects on the cycle.

Q2. Does Dicynone increase the risk of clots or thrombosis?

It does not modify plasma coagulation factors and does not act as a systemic vasoconstrictor, so it is not classified as pro-thrombotic at recommended doses. Nevertheless, use with clinical judgment in patients with a history of thromboembolism.

Q3. When should Dicynone be started for menorrhagia?

Typically 5 days before the expected onset of menstruation, at a dose of 3 × 500 mg tablets daily for 10 days, or as prescribed by a physician.

Q4. Can Dicynone be given together with anticoagulants?

Yes, co-administration is possible when clinically indicated, because etamsylate does not alter coagulation factor levels — but bleeding status should be monitored.

Q5. Can it be used in children and newborns?

Yes. In children the dose is half the adult dose. In premature neonates, it is used to prevent periventricular/intraventricular haemorrhage (10 mg/kg IM every 6 hours for 4 days, starting within 2 hours of birth).

Q6. Is it safe during pregnancy?

It should be avoided during the first trimester. In later pregnancy, use only if clearly needed and under medical supervision.

Q7. Why should the ampoule be given before dextran?

Because dextran, when administered first, may reduce the haemostatic action of etamsylate.

Q8. What should I do if the ampoule solution is discoloured?

Do not use it. Discard the ampoule and use a fresh one; protect ampoules from light during storage.

22. References

1. OM Pharma (Meyrin-Geneva, Switzerland) — Dicynone® / Dicynone® 500 approved product information (Summary of Product Characteristics and patient leaflet).
2. World Health Organization — International Nonproprietary Names (INN) for Pharmaceutical Substances: etamsylate.
3. WHO Collaborating Centre for Drug Statistics Methodology — ATC/DDD Index: B02BX01 – etamsylate.
4. European Pharmacopoeia (Ph. Eur.) monograph: Etamsylate.
5. British Pharmacopoeia — monograph: Ethamsylate.
6. Drugs.com International Drug Names — Etamsylate / Dicynone.
7. DrugBank — Etamsylate entry (drug identifiers and pharmacology).
8. Martindale: The Complete Drug Reference — Etamsylate.
9. Cochrane Database of Systematic Reviews — Etamsylate for the prevention of periventricular haemorrhage in preterm infants.
10. Egyptian Drug Authority (EDA) product registration data for Dicynone presentations locally manufactured by Memphis Co. and Minapharm under licence from OM Pharma – Switzerland.