INSTRUCTION

for medical use of the medicinal product

ACEMIK

Composition:

Active ingredients: tranexamic acid.

Each pill contains tranexamic acid – 500 mg;

Inactive ingredients: microcrystalline cellulose; corn starch, povidone, croscarmellose sodium, stearic acid, colloidal anhydrous silica, magnesium stearate;

pill coating: isopropyl alcohol, methylene chloride, Opadry White film-coating (hydroxypropyl methylcellulose, titanium dioxide (E 171), polyethylene glycol, polysorbate-80)

Dosage form. Film-coated pill.

Basic physical and chemical properties: white or almost white, capsule-like, film-coated pills with scoreline on one side and 500 embossed on the other.

Pharmacotherapeutic group. Antihemorrhagic drugs. Fibrinolysis inhibitors.

ATC code: B02A A02.

Pharmacological properties.

Pharmacodynamics.

Tranexamic acid is an antifibrinolytic, which is a powerful competitive inhibitor of plasminogen to plasmin activation. It is a competitive inhibitor of plasmin at much higher concentrations. It is stated that the inhibitory effect of tranexamic acid on the activation of plasminogen with urokinase is 6-100 times higher, and with streptokinase is 6-40 times higher than the inhibitory effect of aminocaproic acid. The antifibrinolytic effect of tranexamic acid approximately 10 times exceeds the antifibrinolytic effect of aminocaproic acid.

Pharmacokinetics.

Аbsorption. At intravenous administration of tranexamic acid at a dose of 500 mg, the maximum concentration in blood plasma Cmax is achieved immediately, then the concentration decreases during the next 6 hours. The half-life is about 3 hours.
Distribution. Tranexamic acid, administered parenterally, is distributed in two directions: it is absorbed with delay into the cerebrospinal fluid and in the direction of the cells. The volume of distribution is about 33% of body weight.

Tranexamic acid can penetrate the placental barrier, in the breast milk of breast-feeding women, its concentration can reach about 1/100 Cmax.

Excretion. Tranexamic acid is excreted unchanged in urine. 90% of the administered dose is excreted by the kidneys in the first 12 hours after administration (glomerular excretion without tubular reabsorption).

After oral administration, 1.13% and 39% of the administered dose were restored after 3 and 24 hours, respectively.

Plasma concentrations increase in patients with renal insufficiency.

Clinical particulars.

Indications.

Haemorrhage or risk of haemorrhage at the increase of local fibrinolysis:

- menorrhagia;

- bleeding after prostatectomy or bladder intervention;

- constipation of the cervix

- nosebleeds;

- post-traumatic hyphema.

Hereditary angioedema.

Extractions of the tooth in patients with hemophilia.

Contraindications.

Hypersensitivity to tranexamic acid and the components of the drug, severe renal impairment, macroscopic hematuria, high risk of thrombosis, thrombophlebitis, myocardial infarction, subarachnoid bleeding, active thromboembolic disease, history of venous or arterial thrombosis, acute venous or arterial thrombosis, fibrinolytic conditions after coagulopathy due to exhaustion excluding excessive activation of the fibrinolytic system in acute severe bleeding, history of convulsions; colour vision impairment.

Interaction with other medicinal products and other forms of interaction.

Tranexamic acid is not compatible with urokinase, norepinephrine bitartrate, desoxyepinephrine hydrochloride, bitartrate metarmin, dipyridamole and diazepam.

Fibrinolytics.

Highly active prothrombin complex and antifibrinolytics, anti-inhibitor coagulation complex should not be used along with tranexamic acid.

Chlorpromazine.

It is necessary to avoid the combination of chlorpromazine and tranexamic acid in patients with subarachnoid hemorrhage: this may cause a spasm of cerebral vessels and cerebral ischemia as well as may reduce cerebral blood flow.

Oral contraceptives.

Caution should be exercised in patients who use oral contraceptives because of the high risk of thrombosis.

Precautions for use.

In case of renal failure (depending on the increased creatinine level in serum) the dose and number of administrations are reduced. In case of hematuria of renal origin (especially hemophilia) there is a risk of mechanical anuria due to formation of ureteral clots. Some cases of venous and arterial thrombosis or thromboembolism in patients treated with tranexamic acid were reported. In addition, some cases of blockage of central retinal artery and central retinal vein were reported. It is recommended to undergo ophthalmologic examination including visual acuity, colour vision, ocular fundus, and visual fields and evaluate liver function for the patients who take the drug for longer than several days.

Patients with visual impairment should stop treatment.

The increased risk of venous or arterial thrombosis is possible in patients with thromboembolic disease.

Patients with pre-existing thromboembolic disease and family history of thromboembolic disease (patients with thrombophilia) should use tranexamic acid only if there is a direct medical indication and under strict medical supervision.

When using tranexamic acid, cases of convulsions were detected, the majority of which after intravenous use of tranexamic acid in high doses during coronary artery bypass grafting.

Tranexamic acid should not be taken concurrently with Factor IX complex or anti-inhibitor coagulation complex due to the increased risk of thrombosis.

The use of tranexamic acid is not recommended in cases of increased fibrinolysis due to disseminated intravascular coagulation.

Tranexamic acid has been found in the semen in fibrinolytic concentration but it did not affect the sperm motility. Clinical studies have found no effect on fertility.

Patients with irregular menstrual bleeding should not use tranexamic acid until the cause of irregular bleeding has been established. If menstrual bleeding is not adequately reduced by tranexamic acid, an alternative treatment should be considered.

Clinical experience with tranexamic acid in treating menorrhagia in children under 15 years of age is not available.

Pregnancy and lactation.

Tranexamic acid passes into placenta and breast milk. The drug safety studies during pregnancy were not carried out, therefore the drug can be prescribed only if the expected benefit to the pregnant woman outweighs the potential risk to the fetus. If administration of the drug is necessary, the breastfeeding should be discontinued.

Effects on ability to drive and operate machinery.

It is advisable to refrain from driving vehicles and work with other machines during the use of drug.

Routes of administration and dosage.

Adults: the drug is administered orally, regardless of the meal. The pills are swallowed with water. Pills should not be chewed and crushed.

Local fibrinolysis: The recommended dose is 15 to 25 mg/kg, i.e. 2 to 3 pills 500 mg each 2-3 times a day.

Prostatectomy: To prevent and treat hemorrhages in patients with increased risk before or after surgery, tranexamic acid is administered by injection and then by pills 1 g (2 pills of 500 mg) 3-4 times a day until the disappearance of macroscopic hematuria.

Menorrhagia: The recommended dose is 2 pills 500 mg 3 times a day, no more than four days. In case of prolonged menstrual bleeding the dose is increased without exceeding the maximum dose (8 pills 500 mg per day). Do not initiate the treatment before menstrual bleeding.

Nosebleed: In case of periodic bleedings – 2 pills 500 mg 3 times a day for 7 days.

Conization of cervix: 3 pills 500 mg 3 times a day.

Posttraumatic hyphema: 2-3 pills 500 mg 3 times a day. The dosage is 25 mg/kg 3 times a day.

Tooth extraction in patients with hemophilia: The recommended dose is 25 mg/kg of tranexamic acid orally every 8 hours, starting from 1 day before surgery and during 2 to 8 days after it.

Hereditary angioedema: Some patients who know the periods of exacerbations of the disease, usually use 2 to 3 pills 500 mg 2-3 times a day for several days. The other patients should take the drug at the same dose during long-term period of time depending on the disease.

Renal failure: the dosage adjustment is necessary for patients with mild to moderate renal impairment.

Children: The recommended dose is 25 mg/kg. Data on efficacy, dosage, and safety of use of tranexamic acid in children is limited.

Elderly: In case of absence of renal dysfunction the dosage adjustment is not required.

Patients with renal impairment: the dose should be adjusted according to plasma creatinine concentration.

Children.
There is no clinical experience with the use of tranexamic acid in children under the age of 15 with menorrhagia, therefore, the drug should not be used for this category of patients.

Overdose.

Symptoms: nausea, vomiting, abdominal pain, orthostatic hypotension, arterial hypotension, dizziness, headache, convulsions or increased manifestations of other adverse reactions, including the risk of thrombosis.

Treatment: cause vomiting, gastric lavage, take activated charcoal. It is necessary to consume a large amount of fluid to promote renal excretion. Symptomatic treatment is used and, if necessary, anticoagulant therapy.

Adverse reactions.

Gastrointestinal disorders: nausea, vomiting, heartburn, diarrhea, abdominal pain, loss of appetite.

Skin and subcutaneous tissue disorders: rash, itching, urticaria, allergic skin reactions.

Central nervous system disorders: drowsiness, dizziness, convulsions.

Eye disorders: colour vision impairments, visual impairments, congestive retinopathy, occlusion of veins/arteries of retina.

Immune system disorders: hypersensitivity reactions including anaphylaxis.

Vessels disorders: thrombosis of any localization, thromboembolism, hypotension.

Renal disorders: acute necrosis of renal cortical layer.

Storage life. 2 years.

Storage conditions.  

Store in the original package at temperature not exceeding 25°C.

Keep out of reach of children.

Package.

10 pills in a blister. 1 blister in a pack.

Terms of dispensing. On prescription.

Manufacturer. Tulip Lab Pvt. Ltd.

Manufacturer’s registered address.

F-20/21, Ranjangaon MIDC, Tal. Shirur, Dist. Pune, India.

Applicant.  Ananta Medicare Ltd.

Applicant’s registered address.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.

Date of the last review. 23.10.18