Ischemic Stroke Drug Summary

Drug	Dosage	Remarks
Perindopril	Reduction of stroke recurrence: 2.5 mg PO 24 hourly for 2 weeks, then increase to 5 mg PO 24 hourly for a further 2 weeks before introducing Indapamide	Adverse Reactions Hematologic effects (neutropenia, agranulocytosis, anemia, thrombocytopenia); Other effects (cholestatic jaundice, hypotension, syncope, hyperkalemia, cough) Special Instructions Contraindicated in patients with history of angioedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioedema, bilateral or unilateral renal stenosis; concomitant use with Aliskiren-containing products in patients with DM or renal impairment Use with caution in patients with hypertrophic cardiomyopathy, salt or volume depletion, collagen vascular disease, severe aortic and mitral valve stenosis, diabetes, CV disease

Drug	Dosage	Remarks
Direct Factor Xa Inhibitors
Apixaban	Stroke prevention in non-valvular AF: 5 mg PO 12 hourly	Adverse Reactions Hematologic effects (anemia, post-procedural hemorrhage including post-op anemia and wound hemorrhage, contusion); Hepatic effects (elevated gamma-glutamyl transferase and transaminases); GI effects (gingival hyperplasia, nausea) Special Instructions Contraindicated in patients with clinically significant active bleeding, hepatic disease associated with coagulopathy leading to clinically relevant bleeding risk Use with caution in patients with moderate or severe renal impairment. Dose may be reduced in the following: Apixaban: 2.5 mg PO 12 hourly in patients with ≥2 of the following: Age ≥80 years old, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (133 micromol/L) Edoxaban: 30 mg PO 24 hourly in patients with ≥1 of the following: Weight ≤60 kg, CrCl 15-50 mL/min, or using P-glycoprotein (P-gp) inhibitors Rivaroxaban: 15 mg PO 24 hourly if CrCl 15-49 mL/min Use with caution in patients with hepatic impairment, hip fracture surgery, congenital or acquired bleeding disorders, uncontrolled severe arterial hypertension, active ulcerative GI disease, recent GI ulcerations, vascular retinopathy, recent intracranial hemorrhage or ICH, intraspinal or intracerebral vascular abnormalities, epidural/spinal anesthesia or spinal puncture, shortly after brain, spinal or ophthalmologic surgery, women of childbearing potential Monitor for signs of neurological impairment Discontinue use in severe hemorrhage
Edoxaban	Stroke prevention in non-valvular AF: 60 mg PO 24 hourly
Rivaroxaban	Stroke prevention in non-valvular AF: 20 mg PO 24 hourly with evening meal Max dose: 20 mg/day
Direct Thrombin Inhibitor
Dabigatran etexilate (Dabigatran)	Stroke prevention in non-valvular AF: 150 mg PO 12 hourly	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 patients with hepatic impairment, moderate renal impairment, increased hemorrhagic risk, spinal/epidural anesthesia, lumbar puncture Dose may be reduced to 110 mg PO 12 hourly in patients with age ≥80 years old, concomitant use of Verapamil, or increased risk of bleeding Discontinue use in patients who develop acute renal failure
Enzyme
Alteplase (rt-PA)	0.9 mg/kg IV over 60 minutes starting with 10% of total dose given as initial IV bolus over 1 minute Max dose: 90 mg	Adverse Reactions Hematologic effects (hemorrhage especially from puncture sites, severe internal bleeding, intracranial hemorrhage has occurred); GI effects (nausea/vomiting); Other effects (fever, chills with back and abdominal pain) Rarely, allergic reactions (rashes, flushing, urticaria, anaphylactic reactions) Infusion may be associated with hypotension Special Instructions Please see section on Evaluation for inclusion/exclusion criteria Patient should be in ICU or stroke unit for monitoring Neurological assessments should be done every 15 minutes during infusion then every 30 minutes for next 6 hours then every hour until 24 hours from treatment Measure BP every 15 minutes during the first 2 hours then every 30 minutes for the next 6 hours then every hour until 24 hours from treatment Increase frequency of BP monitoring if SBP ≥180 mmHg or DBP ≥105 mmHg Should not be administered in patients receiving LMWH within previous 24 hours If patient suffers from severe headache, nausea/vomiting, acute hypertension (signs of possible intracranial hemorrhage): Discontinue rt-PA if still being administered Obtain urgent CT scan Placement of NGTs, catheters or invasive procedures may be delayed
Tenecteplase (TNK-tPA)	<60 kg: 15 mg IV bolus as a single dose 60-<70 kg: 17.5 mg IV bolus as a single dose 70-<80 kg: 20 mg IV bolus as a single dose 80-<90 kg: 22.5 mg IV bolus as a single dose >90 kg: 25 mg IV bolus as a single dose IV bolus should be administered within 3 hours of onset of symptoms	Adverse Reactions CV effects (heart failure, cardiogenic shock) Rarely, allergic reactions (anaphylaxis, angioedema) Special Instructions Contraindicated in patients with active hemorrhage, hypoglycemia (<50 mg/dL), coagulopathy, current use of direct factor Xa or thrombin inhibitors Use with caution in patients with systolic blood pressure >175 mmHg or diastolic blood pressure >110 mmHg, significant hepatic dysfunction, recent major surgery, acute pericarditis, bacterial endocarditis Should not be administered in patients receiving LMWH within previous 24 hours
Heparinoid
Sulodexide	600 LSU IM/IV injection 24 hourly for 15-20 days then continue treatment with 250-500 LSU PO 12 hourly for 30-40 days Repeat treatment cycle at least twice yearly	Adverse Reactions Injection: Occasionally pain, burn and hematoma at injection site Oral: Occasionally GI disorders eg nausea/vomiting, epigastralgia Special Instructions Should be taken on an empty stomach, 30 minutes before meals Contraindicated in patients with hypersensitivity to Heparin-like products, diathesis and hemorrhagic diseases Periodically monitor hemocoagulative parameters
Platelet Aggregation Inhibitors Excluding Heparin
Aspirin1	Acute phase treatment: 160-325 mg PO as a single dose followed by lower dose (50-325 mg) PO 24 hourly Secondary prevention: 75-325 mg PO 24 hourly	Adverse Reactions GI effects (GI upset which may be minimized with food and with use of enteric-coated formulation, GI irritation like erosion, ulceration); Hematologic effects (increase in bleeding time, decrease in platelet adhesiveness, hemorrhage); Hypersensitivity reactions Special Instructions Contraindicated in patients with active pathological bleeding (eg peptic ulcer, intracranial hemorrhage), known allergy, hemophilia, hemorrhagic disorders, severe renal or hepatic impairment Ensure benefit outweighs the risk before using concomitantly with drugs that increase risk of bleeding (eg thrombolytics, NSAIDs)
Aspirin/Dipyridamole	Secondary prevention: Aspirin 25 mg/Dipyridamole 200 mg 1 cap PO 12 hourly	Adverse Reactions CNS effects (headache, fatigue, amnesia, seizure, confusion, somnolence); GI effects (abdominal pain, dyspepsia, nausea/vomiting, diarrhea, GI bleeding); Neuromuscular effects (arthralgia, back pain, arthritis, myalgia); Hematologic effects (hemorrhage, anemia, epistaxis); CV effects (cardiac failure, syncope); Other effects (cough, hypersensitivity reactions) Special Instructions Contraindicated in patients with active pathological bleeding, severe liver and renal impairments Use with caution in hypotension, unstable angina and/or recent MI
Cilostazol	Secondary prevention: 100 mg PO 12 hourly or 200 mg PO 24 hourly	Adverse Reactions CNS effects (headache, dizziness, vertigo); GI effects (abnormal stools, diarrhea, nausea, abdominal pain, flatulence); Respiratory effects (rhinitis, pharyngitis, cough); CV effects (peripheral edema, palpitation, tachycardia); Neuromuscular effects (back pain, myalgia) Special Instructions Contraindicated in patients with known predisposition to bleeding, history of ventricular arrhythmias and heart failure of any severity Use with caution in patients with severe hepatic and renal impairment
Clopidogrel1	Minor ischemic stroke (NIHSS ≤3): 300 mg PO loading dose, followed by 75 mg PO 24 hourly and Aspirin 75-100 mg PO 24 hourly Start Clopidogrel and Aspirin treatment within 24 hours of the event and continue for 21 days followed by single antiplatelet therapy Secondary prevention: 75 mg PO 24 hourly	Adverse Reactions Hematologic effects (hemorrhage, purpura, epistaxis; blood dyscrasias, including neutropenia and thrombotic thrombocytopenic purpura, have occurred); Dermatologic effects (rash, pruritus); GI effects (abdominal pain, nausea/vomiting, dyspepsia, constipation) Special Instructions Contraindicated in patients with active bleeding, severe liver impairment Concurrent use of drugs known to inhibit CYP2C19 (eg Omeprazole, Esomeprazole, Cimetidine, Fluconazole, Ketoconazole, Voriconazole, Etravirine, Felbamate, Fluoxetine, Fluvoxamine and Ticlopidine) should be avoided Separating the time of administration between the drugs does not reduce the chance of interaction If possible, discontinue use 5-7 days prior to elective surgery
Clopidogrel/Aspirin	Secondary prevention: Clopidogrel 75 mg/Aspirin 75 mg or Clopidogrel 75 mg/Aspirin 100 mg 1 tab or cap PO 24 hourly	Adverse Reactions Hematologic effects (epistaxis, hematoma, bruising); GI effects (GI bleeding, diarrhea, abdominal pain, indigestion, heartburn; less commonly: nausea/vomiting, constipation, gastric ulcer); Other effects (headache, rashes, itching, dizziness, sensation of tingling and numbness) Special Instructions May be taken with or without food Contraindicated in patients with asthma, runny nose, nasal polyps, active bleeding (eg active gastric ulcer, intracranial bleeding), severe liver and kidney disease Use with caution in patients at risk for bleeding (eg gastric ulcer), those with blood disorders that predispose to extensive bleeding, ischemic stroke in the last 7 days, presence of mild-moderate kidney or liver disease, a recent serious injury or a recent surgery
Ticagrelor	Acute ischemic stroke (NIHSS ≤5) or high-risk TIA: 180 mg PO loading dose in combination with Aspirin then continue with 90 mg PO 12 hourly in combination with Aspirin x 30 days	Adverse Reactions Hematologic effects (blood disorder bleeding, post-procedural hemorrhage, traumatic bleedings); GI effects (GI hemorrhage, diarrhea, nausea); CNS effects (syncope, dizziness, vertigo); Other effects (hyperuricemia, gout, dyspnea, hypotension, pruritus) Special Instructions May be taken with or without food Contraindicated in patients with active pathological bleeding (eg peptic ulcer), history of intracranial hemorrhage, severe hepatic impairment Use with caution in patients at risk for bleeding (eg due to recent trauma or surgery, active or recent GI bleeding, moderate hepatic impairment), increased risk of bradycardia (eg patients with sick sinus syndrome or 2nd- to 3rd-degree AV block without pacemaker)
Ticlopidine	Secondary prevention: 250 mg PO 12-24 hourly	Adverse Reactions Metabolic effects (elevation of cholesterol and triglyceride levels); GI effects (diarrhea, nausea/vomiting, dyspepsia, GI pain, flatulence, anorexia); Dermatologic effects (rash, purpura, pruritus); Hematologic effects (neutropenia, thrombotic thrombocytopenia have occurred); Hepatic effects (elevation in alkaline phosphatase level, reports of hepatitis and cholestatic jaundice) Special Instructions Contraindicated in patients with active pathological bleeding (peptic ulcer disease, intracranial hemorrhage), hemorrhagic diatheses, patients with history of thrombocytopenia, neutropenia or agranulocytosis, severe liver dysfunction CBC with differential and platelet counts should be taken at the start of treatment then every 2 weeks for the first 3 months of therapy and within 2 weeks of discontinuation of Ticlopidine (if discontinued within the first 3 months of treatment) If possible, discontinue use 10-14 days prior to elective surgery
Triflusal	Secondary prevention: 600-900 mg/day PO in single or divided doses	Adverse Reactions GI effects (dyspepsia, abdominal pain, nausea/vomiting, constipation, flatulence, anorexia); CNS effect (headache) Special Instructions Contraindicated in patients with active, antecedent or complicated peptic ulcer, active bleeding and hypersensitivity to salicylates Use with caution in patients with hepatic and renal impairment
Vitamin K Antagonist
Warfarin	Secondary prevention: Individualize dose based on PT/INR Initial dose: 2-5 mg PO 24 hourly 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, hepatic dysfunction, pancreatitis); Other effects (alopecia, skin reactions) 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, active GI ulceration, 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) has been achieved Then INR is monitored 2-3x/week for 2 weeks Then INR is monitored weekly or less often depending on the stability of INR

¹Combination product with Rosuvastatin is available. Please see the latest MIMS for specific formulations and prescribing information.

All dosage recommendations are for non-pregnant and non-breastfeeding women, and non-elderly adults with normal renal and hepatic function unless otherwise stated.  
Not all products are available or approved for above use in all countries.  
Products listed in the Drug Summary are based on indications stated in the locally approved product monographs.   
Please refer to local product monographs in Related MIMS Drugs for country-specific prescribing information.