| Drug |
Dosage |
Remarks |
| Direct Thrombin Inhibitor |
| Dabigatran etexilate |
Treatment of acute DVT and/or pulmonary embolism: 150 mg PO 12 hourly (after 5-10 days of parenteral anticoagulation)
Prevention of recurrent DVT and/or pulmonary embolism: 150 mg PO 12 hourly following treatment with a parenteral anticoagulant for at least 5 days |
Adverse Reactions
- Hematologic effects (hemorrhage, anemia, hematoma, thrombocytopenia); Renal effect (hematuria); GI effects (dyspepsia, nausea/vomiting, GI hemorrhage, abdominal pain, diarrhea, gastroesophagitis, abnormal hepatic function); Other effects (wound secretion, post-procedural discharge)
Special Instructions
- Contraindicated in patients with severe renal impairment, hemorrhagic manifestations, bleeding diathesis, patients with spontaneous or pharmacological hemostatic impairment, organ lesions at risk of clinically significant bleeding (including hemorrhagic stroke within the last 6 months, patients on concomitant therapy with systemic Ketoconazole, prosthetic heart valve replacement)
- Use with caution in hepatic impairment, renal insufficiency, increased hemorrhagic risk, spinal/epidural anesthesia, lumbar puncture
- Discontinue use in patients who develop acute renal failure
|
| Enzymes |
| Alteplase (rt-PA) |
Acute massive pulmonary embolism
Loading dose: 10 mg as an IV bolus over 1-2 minutes
Followed by IV infusion over 2 hours of:
<65 kg: Up to a total dose of 1.5 mg/kg
≥ 65 kg: 90 mg
Max total dose: 100 mg
(1.5 mg/kg in patients <65 kg)
|
Adverse Reactions
- Hematologic effects (hemorrhage especially from puncture sites, severe internal bleeding, intracranial hemorrhage has occurred); GI effects (nausea/vomiting, abdominal pain)
- Rarely: Allergic reactions (rashes, flushing, urticaria and rarely anaphylactic and serum sickness-like symptoms)
- Infusion may be associated with hypotension (both direct and as a result of reperfusion), bradycardia and arrhythmias may occur because of reperfusion
- Break up of clots may occasionally cause emboli elsewhere hence the need for Heparin prophylaxis
Special Instructions
- Absolutely contraindicated in patients with hemorrhagic stroke or stroke of unknown origin at any time (including intracerebral hemorrhage), major trauma or surgery or head injury in the past 3 months, ischemic stroke within the past 6 months, CNS damage or tumors, intracranial vascular lesion, severe coagulation disorders, active major bleeding, known increased risk for bleeding (severe bleeding diathesis), suspected aortic dissection
- Relatively contraindicated in patients with transient ischemic attack within the past 6 months, puncture of a non-compressible vessel, uncontrolled severe hypertension (SBP >180 mmHg, diastolic BP [DBP] >100 mmHg), neurosurgery or ophthalmologic surgery within the last 1 month, ischemic stroke within the last 2 months, GI bleeding, within the last 10 days, active peptic ulcer disease, recent traumatic cardiopulmonary resuscitation (CPR), pregnancy or within 1 week postpartum, infective endocarditis, on oral anticoagulant therapy, advanced liver disease
|
Reteplase (r-PA)
|
Treatment of pulmonary embolism:
Two bolus injections of 10 units each (each bolus is given over 2 minutes) after the onset of symptoms
May repeat dose once, 30 minutes after initial bolus injection
|
Adverse Reactions
- Hematologic effects (hemorrhage, intracranial bleeding); CV effects (hypotension, hypertension, pericarditis, bradycardia, thrombosis)
Special Instructions
- Absolutely contraindicated in patients with hemorrhagic stroke or stroke of unknown origin at any time (including intracerebral hemorrhage), major trauma or surgery or head injury in the past 3 months, ischemic stroke within the past 6 months, CNS damage or tumors, intracranial vascular lesion, severe coagulation disorders, active major bleeding, known increased risk for bleeding (severe bleeding diathesis), suspected aortic dissection
- Relatively contraindicated in patients with transient ischemic attack within the past 6 months, puncture of a non-compressible vessel, uncontrolled severe hypertension (SBP >180 mmHg, diastolic BP [DBP] >100 mmHg), neurosurgery or ophthalmologic surgery within the last 1 month, ischemic stroke within the last 2 months, GI bleeding, within the last 10 days, active peptic ulcer disease, recent traumatic cardiopulmonary resuscitation (CPR), pregnancy or within 1 week postpartum, infective endocarditis, on oral anticoagulant therapy, advanced liver disease
- Use with caution in patients with recent major surgery, CVD, recent GI/GU bleed, hypertension, severe hepatic/renal impairment, arrhythmias, cholesterol embolism
|
Streptokinase
|
Loading dose:
250,000 IU IV over 30 minutes
Followed by:
1.5 MIU/hr IV infusion x 6 hours
or 100,000 IU/hr IV infusion x 72 hours for DVT or x 24 hours for PE or 1,500,000 IU IV infusion over 1-2 hours for PE
Begin Heparin 3-4 hours after Streptokinase infusion or when aPTT is <100 seconds
|
Adverse Reactions
- Hematologic effects (hemorrhage especially from puncture sites, severe internal bleeding, intracranial hemorrhage has occurred); Allergic reactions (rashes, flushing, urticaria and rarely anaphylactic and serum sickness-like symptoms); GI effects (nausea/vomiting); Other effects (fever, chills with back and abdominal pain); Guillain-Barré syndrome has occurred
- Infusion may be associated with hypotension (both direct and as a result of reperfusion), bradycardia and arrhythmias may occur because of reperfusion
- Break up of clots may occasionally cause emboli elsewhere
- Serious allergic reactions may be less likely to occur with Urokinase than with Streptokinase
Special Instructions
- Absolutely contraindicated in patients with hemorrhagic stroke or stroke of unknown origin at any time (including intracerebral hemorrhage), major trauma or surgery or head injury in the past 3 months, ischemic stroke within the past 6 months, CNS damage or tumors, intracranial vascular lesion, severe coagulation disorders, active major bleeding, known increased risk for bleeding (severe bleeding diathesis), suspected aortic dissection
- Relatively contraindicated in patients with transient ischemic attack within the past 6 months, puncture of a non-compressible vessel, uncontrolled severe hypertension (SBP >180 mmHg, diastolic BP [DBP] >100 mmHg), neurosurgery or ophthalmologic surgery within the last 1 month, ischemic stroke within the last 2 months, GI bleeding, within the last 10 days, active peptic ulcer disease, recent traumatic cardiopulmonary resuscitation (CPR), pregnancy or within 1 week postpartum, infective endocarditis, on oral anticoagulant therapy, advanced liver disease
- Anti-streptokinase antibodies are formed after about 5 days after Streptokinase use
- These antibodies may cause resistance or hypersensitivity to subsequent doses of Streptokinase
- Recommend not to administer Streptokinase 5 days-12 months after the first administration (alternative thrombolytic not including Anistreplase may be used)
|
Urokinase
|
Treatment of acute massive pulmonary embolism and extensive acute proximal DVT
Loading dose:
4,400 IU/kg IV infusion over 10-20 minutes
Followed by:
Pulmonary embolism: 4,400 IU/kg/hr continuous IV infusion X 12 hours
DVT: 100,000 IU/hr continuous IV infusion x 48-72 hours or 4,400 IU/kg/hr continuous IV infusion x 12-24 hours
Anticoagulation should be started once aPTT has decreased to <2x the normal control value. If Heparin is used, do not give a loading dose of Heparin
|
| Factor Xa Inhibitors |
| Apixaban |
Treatment of DVT or pulmonary embolism
Initial dose: 10 mg PO 12 hourly x 7 days
Max dose: 20 mg/day
Maintenance dose:
5 mg PO 12 hourly
Max dose: 10 mg/day
Prevention of recurrent DVT and/or pulmonary embolism
2.5 mg PO 12 hourly
To be initiated following completion of 6 months treatment with 5 mg PO 12 hourly for DVT/pulmonary embolism or with another anticoagulant |
Adverse Reactions
- Hematologic effects (anemia, hemorrhage, contusion); GI effect (nausea)
Special Instructions
- Contraindicated in patients with clinically significant active bleeding, hepatic disease with coagulopathy and clinically relevant bleeding risk
- Use with caution in hip fracture surgery, galactose intolerance, glucose-galactose malabsorption, severe renal impairment, hepatic impairment
- Discontinue use in severe hemorrhage
- Monitor for signs of neurological impairment
|
| Edoxaban |
Treatment of DVT and pulmonary embolism and prevention of recurrent DVT and pulmonary embolism:
≤60 kg: 30 mg PO 24 hourly
>60 kg: 60 mg PO 24 hourly
For the treatment of DVT and pulmonary embolism, it is given after 5-10 days of initial therapy with a parenteral anticoagulant
Patients with moderate or severe renal impairment (CrCl 15-50 mL/min), ≤60 kg body weight, or concomitant use of P-gp inhibitors (Ciclosporin, Dronedarone, Erythromycin, Ketoconazole) are given 30 mg PO 24 hourly |
Adverse Reactions
- Hematologic effects (anemia, hemorrhage); GI effect (nausea); Other effects (abnormal LFT, increased blood bilirubin and gamma glutamyl transferase, rash, pruritus)
Special Instructions
- Edoxaban 15 mg is not indicated as monotherapy
- Contraindicated in patients with clinically significant active bleeding or conditions at risk for major bleeding, hepatic disease with coagulopathy and clinically relevant bleeding risk, uncontrolled severe hypertension, concomitant treatment with any other anticoagulants except when switching oral anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter
- Use with caution in patients with an increased risk of bleeding, moderate or severe renal impairment, mild or moderate hepatic impairment, concomitant use of medicines affecting hemostasis
- Perform LFT prior to treatment and CrCl at the start of therapy and thereafter
|
| Fondaparinux (Fondaparin) |
Treatment of DVT and pulmonary embolism
<50 kg:
5 mg SC 24 hourly
50-100 kg:
7.5 mg SC 24 hourly
>100 kg:
10 mg SC 24 hourly
Continue for at least 5 days or until adequate oral coagulation is established (INR 2-3)
Usual treatment duration: 5-9 days
|
Adverse Reactions
- Hematologic effects (hemorrhage, thrombocytopenia, anemia, purpura); Hepatic effect (abnormal LFT); Other effect (edema)
- Less common effects: CNS effects (vertigo, dizziness, headache); CV effect (hypotension); GI effects (nausea/vomiting, dyspepsia, constipation, diarrhea); Dermatologic effects (rash, pruritus); Rare allergic reactions
Special Instructions
- Avoid in patients with clinically significant bleeding, severe renal impairment or in those with confirmed HIT
- Use with caution in patients with an increased risk of hemorrhage; acute GI ulcer, recent intracranial hemorrhage, or shortly after brain, spinal or ophthalmic surgery; use with caution in patients <50 kg, patients with moderate renal impairment, severe hepatic impairment, with history of HIT, elderly >75 years old
- Consider risk versus benefit before neuraxial intervention is employed in patients anticoagulated or to be anticoagulated for thromboprophylaxis
- Monitoring of platelets is recommended at baseline and at the end of treatment
|
Rivaroxaban
|
Treatment of DVT and pulmonary embolism
Days 1-21: 15 mg PO 12 hourly
Max dose: 30 mg/day
Days 22 onwards: 20 mg PO 24 hourly
Max dose: 20 mg/day
|
Adverse Reactions
- Hematologic effects (hemorrhage, anemia, decreased hemoglobin); Hepatic effect (increased ALT and AST); CNS effects (dizziness, headache, syncope); CV effects (tachycardia, hypotension); GI effect (nausea); Dermatologic effects (pruritus, rashes); Other effects (fever, peripheral edema, postprocedural hemorrhage)
Special Instructions
- Contraindicated in patients with clinically significant active bleeding, pregnant, lactating and hepatic disease associated with coagulopathy that can lead to relevant risk of bleeding
- Use with caution in patients with hemorrhagic risk, lactose or galactose intolerance, and those with moderate to severe renal impairment
|
Heparin Group
|
| Bemiparin sodium |
Treatment of DVT with or without pulmonary embolism:
115 IU anti-Xa/kg/day SC during 7±2 days which corresponds to:
<50 kg: 5,000 IU anti-Xa
50-70 kg: 7,500 IU anti-Xa
70-100 kg: 10,000 IU anti-Xa
100-120 kg: 12,500 IU anti-Xa
>120 kg: 115 IU anti-Xa/kg/day
Patients with DVT and transitory risk factors
3,500 IU/day SC up to a max of 3 months |
Adverse Reactions
- Hematologic effects (hemorrhage, thrombocytopenia); Injection site reaction; Rare hypersensitivity reactions (anaphylaxis); Effects that may occur with long-term use (osteoporosis, alopecia)
- Sulodexide: Nausea/vomiting, diarrhea, epigastralgias
Special Instructions
- Avoid in patients with active major bleeding, patients with positive in vitro test for antiplatelet Ab to the specific heparin, injury or surgery to CNS, eyes or ears
- Use with caution in patients with hemorrhagic disorders (including history of HIT), peptic ulcer, cerebrovascular disorders, uncontrolled hypertension, hepatic or renal impairment, surgery at sites at risk for hemorrhage, hypersensitivity to Heparin
- Consider risk versus benefit before neuraxial intervention is employed in patients anticoagulated or to be anticoagulated for thromboprophylaxis
- Monitoring of platelets at baseline and periodically during treatment is recommended
|
Dalteparin sodium
|
200 IU/kg SC 24 hourly or
100 IU/kg SC 12 hourly for patients with increased risk of bleeding
Max dose: 18,000 IU/day
|
| Enoxaparin |
1 mg/kg SC 12 hourly x 5-10 days1 or
Uncomplicated patients with low risk of VTE recurrence:
1.5 mg/kg (150 anti-Xa IU/kg) SC 24 hourly x 5-10 days
Initiate oral anticoagulant therapy when appropriate
|
Heparin
(Unfractionated Heparin, UFH)
|
Weight-adjusted dosing based on nomogram
or
UFH IV infusion:
Loading dose: 5,000 units IV bolus injection
Loading dose for severe pulmonary embolism: 10,000 units IV bolus injection
Followed by: 18 units/kg/hr or 1,000-2,000 units/hr continuous IV infusion
(adjust dose based on aPTT)
or
5,000-10,000 units intermittent IV injection 4-6 hourly
(adjust dose based on aPTT)
or
SC UFH:
15,000 units SC 12 hourly or 10,000 units SC 8 hourly (adjust dose based on aPTT) |
Nadroparin calcium
|
As 9,500 anti-Xa IU/mL injection: 86 anti-Xa iu/kg SC 12 hourly x 10 days
or
As 19,000 anti-Xa IU/mL injection: 171 anti-Xa IU/kg SC 24 hourly x 10 days
|
| Parnaparin sodium |
6,400 anti-Xa IU SC 24 hourly x 7-10 days
|
| Reviparin sodium |
35-45 kg: 3,500 anti-Xa IU SC 12 hourly
46-60 kg: 4,200 anti-Xa IU SC 12 hourly
>60 kg: 6,300 anti-Xa IU SC 12 hourly
Doses to be given with an oral anticoagulant x 5-7 days |
Sulodexide
|
600 LSU IM/IV injection 24 hourly x 15-20 days then continue with 250-500 LSU PO 12 hourly x 30-40 days
Repeat the treatment cycle at least twice yearly |
Tinzaparin sodium
|
175 anti-Xa IU/kg SC 24 hourly x at least 6 days and until adequate oral anticoagulation is established
|
| Platelet Aggregation Inhibitor Excluding Heparin |
Aspirin2 (Acetylsalicylic acid)
|
Prophylaxis against DVT and pulmonary embolism: 100 mg PO 24 hourly or 81-200 mg PO 24 hourly or 300-325 mg PO 48 hourly |
Adverse Reactions
- Hematologic effects (thrombocytopenia, anemia); GI effects (gastric hemorrhage, nausea/vomiting, dyspepsia); Other effects (salicylate sensitivity, tinnitus, severe hypoglycemia, Reye’s syndrome)
Special Instructions
- Contraindicated in patients with salicylate-induced asthma, active peptic ulcer, hemorrhagic diathesis, severe cardiac or renal failure
- Combination with >15 mg/week Methotrexate is contraindicated
- Use with caution in patients with renal impairment, G6PD insufficiency, flu, chickenpox, hemorrhagic fever, GI ulceration, asthma
|
| Vitamin K Antagonist |
Warfarin
|
Initial dose: 2-10 mg PO 24 hourly
May initially consider 10 mg PO 24 hourly x 2 days in patients eligible for outpatient initiation
Followed by subsequent dose that should be adjusted to target INR = 2.5 (INR range 2.0-3.0) and continue therapy for at least 3 months
Maintenance dose:
2-10 mg PO 24 hourly |
Adverse Reactions
- Hemorrhage can occur even within therapeutic INR levels
- Less common effects: Cholesterol embolization (skin necrosis and purple discoloration of the toes); GI effects (nausea/vomiting, diarrhea); Other effects (alopecia, skin reactions, hepatic dysfunction, pancreatitis)
Special Instructions
- Patients should be counseled on the risks of therapy along with drug and food interactions
- Avoid in patients with active or at risk of hemorrhage, peptic ulcer disease, severe wounds, cerebrovascular disorders and bacterial endocarditis
- Use with extreme caution or not at all in patients with severe renal or hepatic impairment
- INR monitoring is usually performed daily until the therapeutic range (2.0-3.0) is achieved
- Then INR is monitored 2-3x/week x 2 weeks
- Then INR is monitored weekly or less often depending on the stability of INR
|
