Active ingredient in Dabiclot is Dabigatran etexilate mesilate, it belongs to a group of medicines called anticoagulants.
Each capsule contains Dabigatran etexilate mesilate 110mg/150mg. Packing: 10*10 strips
Pharmacodynamic properties
Pharmacotherapeutic group: Antithrombotic agents, direct thrombin inhibitors.
Mechanism of Action: Dabigatran is a potent, competitive, reversible direct thrombin inhibitor and is the main active principle in plasma. Since thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of thrombus. Dabigatran inhibits free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation.
Pharmacokinetic properties: After oral administration, Dabigatran etexilate is rapidly and completely converted to Dabigatran, which is the active form in plasma. The cleavage of the prodrug Dabigatran etexilate by esterase-catalyzed hydrolysis to the active principle Dabigatran is the predominant metabolic reaction. The absolute bioavailability of Dabigatran following oral administration of Dabigatran was approximately 6.5 %after oral administration of Dabigatran in healthy volunteers, the pharmacokinetic profile of Dabigatran in plasma is characterized by a rapid increase in plasma concentrations with Cmax attained within 0.5 and 2.0 hours post administration.
Absorption: A study evaluating post-operative absorption of Dabigatran etexilate, 1-3 hours following surgery, demonstrated relatively slow absorption compared with that in healthy volunteers, showing a smooth plasma concentration-time profile without high peak plasma concentrations. Peak plasma concentrations are reached at 6 hours following administration in a postoperative period due to contributing factors such as anesthesia, GI paresis, and surgical effects independent of the oral medicinal product formulation. It was demonstrated in a further study that slow and delayed absorption is usually only present on the day of surgery. On subsequent days absorption of Dabigatran is rapid with peak plasma concentrations attained 2 hours after medicinal product administration. Food does not affect the bioavailability of Dabigatran etexilate but delays the time to peak plasma concentrations by 2 hours. Cmax and AUC were dose proportional. The oral bioavailability may be increased by 75 % after a single dose and 37 % at steady state compared to the reference capsule formulation when the pellets are taken without the Hydroxypropyl methylcellulose (HPMC) capsule shell.
Distribution: Low (34-35 %) concentration independent binding of Dabigatran to human plasma proteins was observed. The volume of distribution of Dabigatran of 60-70 L exceeded the volume of total body water indicating moderate tissue distribution of Dabigatran.
Biotransformation: After oral administration, Dabigatran etexilate is rapidly and completely converted to Dabigatran, which is the active form in plasma. The cleavage of the prodrug Dabigatran etexilate by esterase catalyzed hydrolysis to the active principle Dabigatran is the predominant metabolic reaction. Dabigatran is subject to conjugation forming pharmacologically active acyl glucuronides. Four positional isomers, 1-O, 2-O, 3-O, 4-O-acylglucuronide exist, each accounts for less than 10% of total Dabigatran in plasma. Traces of other metabolites were only detectable with highly sensitive analytical methods.
Elimination: Plasma concentrations of Dabigatran showed a bi exponential decline with a mean terminal half-life of 11 hours in healthy elderly subjects. After multiple doses a terminal half-life of about 12-14 hours was observed. The half-life was independent of dose. Half-life is prolonged if renal function is impaired.
Primary prevention of Venous Thromboembolism in orthopedic Surgery
| Clinical Conditions | Dose recommendation |
| Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors (SPAF) | Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors (SPAF) 300 mg DABICLOT taken as one 150 mg capsule twice daily |
| Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT, and PE in adults (DVT/PE)/td> | 300 mg t DABICLOT taken as one 150 mg capsule twice daily following treatment with a parenteral anticoagulant for at least 5 days |
| Dose reduction recommended | daily dose of 220 mg DABICLOT taken as one 110 mg capsule twice daily |
| Patients aged ≥80 years | |
| Patients who receive concomitant verapamil | |
| Dose reduction for consideration | |
| Patients between 75-80 years | Daily dose of DABICLOT of 300 mg or 220 mg should be selected based on an individual assessment of the thromboembolic risk and the risk of bleeding. |
| Patients with moderate renal impairment (CrCL 30-50 mL/min | |
| Patients with gastritis, esophagitis or gastro esophageal reflux | |
| Other patients at increased risk of bleeding |
Duration of Use
The duration of use of DABICLOT in the indications SPAF, DVT and PE are shown in table:
| Indication | Duration of Use |
| SPAF | Therapy should be continued long term. |
| DVT/PE | The duration of therapy should be individualized after careful assessment of the treatment benefit against the risk for bleeding. Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, and immobilization) and longer durations should be based on permanent risk factors or idiopathic DVT or PE. |
Patients at risk of bleeding:
Patients with an increased bleeding risk should be closely monitored clinically (looking for signs of bleeding or anemia). Dose adjustment should be decided at the discretion of the physician, following assessment of the potential benefit and risk to an individual patient . A coagulation test may help to identify patients with an increased bleeding risk caused by excessive Dabigatran exposure. When excessive Dabigatran exposure is identified in patients at high risk of bleeding, a reduced dose of 220 mg taken as one 110 mg capsule twice daily is recommended. When clinically relevant bleeding occurs, treatment should be interrupted. For subjects with gastritis, esophagitis, or gastro esophageal reflux, a dose reduction may be considered due to the elevated risk of major gastro-intestinal bleeding.
Renal impairment:
Treatment with DABICLOT in patients with severe renal impairment (CrCL < 30 mL/min) is contraindicated .No dose adjustment is necessary in patients with mild renal impairment (CrCL 50- ≤ 80 mL/min). For patients with moderate renal impairment (CrCL 30-50 mL/min) the recommended dose of DABICLOT is also 300 mg taken as one 150 mg capsule twice daily. However, for patients with high risk of bleeding, a dose reduction of DABICLOT to 220 mg taken as one 110 mg capsule twice daily should be considered. Close clinical surveillance is recommended in patients with renal impairment.
Concomitant use of DABICLOT with mild to moderate P-glycoprotein (P-gp) inhibitors
, i.e. Amiodarone, quinidine or verapamil. No dose adjustment is necessary for concomitant use of Amiodarone or quinidine. Dose reductions are recommended for patients who receive concomitantly verapamil .In this situation DABICLOT and verapamil should be taken at the same time.
Weight:
No dose adjustment is necessary, but close clinical surveillance is recommended in patients with a body weight < 50 kg.
Gender:
No dose adjustment is necessary
Pediatrics population
There is no relevant use of DABICLOT in the Pediatric population for the indication of prevention of stroke and systemic embolism in patients with NVAF. For the indication DVT/PE, the safety and efficacy of DABICLOT in children from birth to less than 18 years of age have not yet been established.
DABICLOT is for oral use. The capsules can be taken with or without food. DABICLOT should be swallowed as a whole with a glass of water, to facilitate delivery to the stomach.
They are ranked under headings of System Organ Class (SOC) and frequency using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
| Frequency | ||
| SOC / Preferred term. | Stroke and systemic embolism prevention in patients with atrial fibrillation | DVT/PE treatment and DVT/PE prevention |
| Blood and lymphatic system disorders | ||
| Anemia | Common | |
| Hemoglobin decreased | Uncommon | Not Known |
| Thrombocytopenia | Uncommon | Rare |
| Hematocrit decreased | Rare | Not Known |
| Immune system disorder | ||
| Drug hypersensitivity | Uncommon | Uncommon |
| Rash | Uncommon | Uncommon |
| Pruritus | Uncommon | Uncommon |
| Anaphylactic reaction | Rare | Rare |
| Urticaria | Rare | Rare |
| Angioedema | Rare | Rare |
| Bronchospasm | Not known | Not known |
| Nervous system disorders | ||
| Intracranial hemorrhage | Uncommon | Rare |
| Vascular disorders | ||
| Hematoma | Uncommon | Common |
| Uncommon | Common | |
| Respiratory, thoracic and mediastinal disorders | ||
| Epistaxis | Common | Common |
| Hemoptysis | Uncommon | Uncommon |
| Gastrointestinal disorders | ||
| Gastrointestinal hemorrhage | Common | Common |
| Abdominal pain | Common | Uncommon |
| Diarrhea | Common | Uncommon |
| Dyspepsia | Common | Common |
| Nausea | Common | Uncommon |
| Rectal hemorrhage | Uncommon | Common |
| Haemorrhoidal hemorrhage | Uncommon | Uncommon |
| Gastrointestinal ulcer | Uncommon | Uncommon |
| Gastro esophagitis | Uncommon | Uncommon |
| Vomiting | Uncommon | Uncommon |
| Dysphagia | Uncommon | Uncommon |
| Gastro esophageal reflux disease | Uncommon | Rare |
| Hepatobiliary disorders | ||
| Hepatic function abnormal/ Liver function Test abnormal | Uncommon | Uncommon |
| Alanine aminotransferase increased | Uncommon | Uncommon |
| aspartate aminotransferase increased | Uncommon | Uncommon |
| Hepatic enzyme increased | Rare | Uncommon |
| Hyperbilirubinaemia | Rare | Not Known |
| Skin and subcutaneous tissue disorder | ||
| Skin hemorrhage | Common | Common |
| Musculoskeletal and connective tissue disorders | ||
| Haemarthrosis | Rare | Uncommon |
| Renal and urinary disorders | ||
| Genitourological hemorrhage, including hematuria | Common | Common |
| General disorders and administration site conditions | ||
| Injection site hemorrhage | Rare | Rare |
| Catheter site hemorrhage | Rare | Rare |
| Injury, poisoning and procedural complications | ||
| Traumatic hemorrhage | Rare | Uncommon |
| Incision site hemorrhage | Rare | Rare |
Hemorrhagic risk
DABICLOT should be used with caution in conditions with an increased risk of bleeding or with concomitant use of medicinal products affecting hemostasis by inhibition of platelet aggregation. Bleeding can occur at any site during therapy with DABICLOT. An unexplained fall in hemoglobin and/or hematocrit or blood pressure should lead to a search for a bleeding site. In clinical trials, DABICLOT was associated with higher rates of major gastrointestinal (GI) bleeding. An increased risk was seen in the elderly (≥ 75 years) for the 150 mg twice daily dose regimen. Further risk factors comprise co-medication with platelet aggregation inhibitors such as clopidogrel and acetylsalicylic acid (ASA) or non-steroidal anti-inflammatory drugs (NSAID), as well as the presence of esophagitis, gastritis or gastro esophageal reflux.
Women of childbearing potential
Women of childbearing potential should avoid pregnancy during treatment with Dabiclot.
Pregnancy
There is limited amount of data from the use of Dabiclot in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Dabiclot should not be used during pregnancy unless clearly necessary.
Breast-feeding
There are no clinical data of the effect of Dabigatran on infants during breast-feeding. Breast-feeding should be discontinued during treatment with Dabiclot.