Cardiovascular Disease Prevention Drug Summary

• GI effects (dyspepsia, GI irritation, nausea/vomiting); Hematologic effects (increased bleeding time, decreased platelet adhesiveness, hemorrhage); Hypersensitivity reactions

• GI upset may be minimized by administering with food and with use of enteric-coated formulation
• Contraindicated in patients with active pathological bleeding (eg peptic ulcer, intracranial hemorrhage), known allergy, hemophilia, hemorrhagic disorders, severe renal or hepatic impairment
• Use with caution in patients with GI mucosa lesions, allergic disorders, anemia, uncontrolled hypertension, glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Ensure that benefit outweighs the risk prior to use in combination with Warfarin, Heparin, thrombolytics, NSAIDs and other drugs that increase the risk of bleeding

• Hematologic effects (hemorrhage, purpura, epistaxis; blood dyscrasias, including neutropenia, thrombotic thrombocytopenic purpura have occurred); Dermatologic effects (rash, pruritus); GI effects (abdominal pain, nausea/vomiting, dyspepsia, constipation)

• Contraindicated in patients with active bleeding or 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

• GI effects (nausea/vomiting, diarrhea); Dermatologic effect (rash); Hepatic effects (elevated LFT, rarely hepatitis and cholestatic jaundice); Hematologic effects (neutropenia, thrombotic thrombocytopenic purpura, agranulocytosis, hemorrhage)

• Contraindicated in patients with active bleeding, hemorrhagic diatheses, patients with history of leukopenia, thrombocytopenia or agranulocytosis, history of stroke or TIA, severe hepatic impairment
• Use with caution in patients with propensity to bleed, low body weight, or who will undergo CABG and other surgical procedure
• Use with caution when combining with Warfarin, Heparin, thrombolytics, NSAIDs and other drugs that increase the risk of bleeding

• Hematologic effect (bleeding); Respiratory effect (dyspnea); CNS effects (headache, dizziness); ENT effects (epistaxis, vertigo); GI effects (abdominal pain, nausea/vomiting, constipation, diarrhea); Metabolic effect (hyperuricemia); Dermatologic effects (rash, pruritus); Other effect (post-procedural hemorrhage)

• Contraindicated in patients with active pathological bleeding, intracranial hemorrhage history, known allergy, or severe hepatic impairment 
• Use with caution in patients with increased risk for bradycardia
• Avoid abrupt discontinuation of therapy or therapy lapses

• Hemorrhage can occur even within therapeutic international normalized ratio (INR) levels
• Other less common effects: Cholesterol embolization (skin necrosis and purple discoloration of the toes); GI effects (nausea/vomiting, diarrhea, hepatic dysfunction, pancreatitis); Other effects (alopecia, fever, skin reactions)

• Dosage adjustments must be guided by regular monitoring of INR
• Patients should be counseled on the risks of therapy along with drug and food interactions
• Avoid in patients with hemorrhagic states, bleeding from GI tract, genitourinary tract or respiratory tract, in patients with severe wounds, infective endocarditis, impaired hepatic or renal function, with hypertension, cerebrovascular hemorrhage, cerebral or aortic aneurysms, pericarditis, pericardial effusion, polyarthritis, threatened abortion
• Use with caution in patients with vitamin K deficiency, hyperthyroidism, polycythemia vera, vasculitis and severe diabetes

Adverse Reactions

• GI effects (nausea/vomiting, diarrhea, dyspepsia, gastroesophageal reflux, acute pancreatitis); CNS effects (dizziness, headache); Other effects (rash, hypersensitivity reactions)
• Uncommon effects include renal impairment and acute renal failure

Special Instructions

• Avoid use in patients with type 1 DM or DKA, multiple endocrine neoplasia syndrome type 2, personal or family history of medullary thyroid carcinoma
• Discontinue use if acute pancreatitis occurs
• Contraindicated in patients with hypersensitivity to the active substance or to any of the excipients

Adverse Reactions

• GU effects (polyuria, dysuria, vulvovaginitis, balanitis, increased susceptibility to infections); Renal effect (acute kidney injury); Hematologic effect (increased hematocrit); GI effects (nausea, constipation); CV effects (hypotension, decreased blood volume); Other effects (dyslipidemia, increased creatinine and urea levels, hypoglycemia, rash, hyperhidrosis, back pain, euglycemic diabetic ketoacidosis)
• Electrolyte disturbances (hyperphosphatemia, hypermagnesemia, hyperkalemia)

Special Instructions

• Monitor kidney function prior to starting therapy and assess periodically during therapy
• Use with caution in patients taking diuretics, NSAIDs and those with decreased blood volume and congestive heart failure
• May need to lower doses of Insulin, sulfonylurea, insulin secretagogues when used concomitantly with SGLT2 inhibitors
• Should not be given in patients with severe renal impairment
  • Canagliflozin can be started in patients with eGFR 45 to <60 mL/min/1.73 m²
  • Dapagliflozin and Empagliflozin treatment can be initiated in patients with eGFR ≥60 mL/min/1.73 m²
  • Discontinue use if eGFR <45 mL/min/1.73 m² is persistent
• Though current evidence suggests that CV and renal benefits appear to be maintained even at eGFR levels as low as 30 mL/min/1.73 m², physicians need to recognize that at a level of CKD stage 3b and lower, the glucose-lowering efficacy of SGLT2 inhibitors is weak
• Consider withholding SGLT2 inhibitors in events that may precipitate diabetic ketoacidosis, eg intercurrent illness, surgery (elective or emergency), trauma, severe carbohydrate restriction
• SGLT2 inhibitors are generally safe for diabetic patients during Ramadan but should be discontinued in select patients whose risk for adverse effects might be increased

• GI effects (abdominal pain, dyspepsia, nausea/vomiting); CNS effects (headache, vertigo); Other effects (rash, gallstones, eczema)
• Myopathy, rhabdomyolysis and myositis may occur 

• Not recommended in patients with severe renal or hepatic dysfunction, gallstones
• Use with caution in mild-moderate renal impairment
• Monitor serum transaminase levels regularly

Adverse Reactions

• Respiratory effects (upper respiratory tract infection, nasopharyngitis, cough); GI effects (gastroenteritis, diarrhea); Other effects (influenza, back pain, injection site reactions, UTI, sinusitis, myalgia, allergic reactions)

Special Instructions

• If serious signs and symptoms of allergic reactions occur, discontinue therapy
• Measure LDL-C levels 4-8 weeks after initiation or titration of treatment

• Monotherapy: Diarrhea, abdominal pain, flatulence, fatigue
• When administered with a statin: Increased ALT and/or AST, headache, myalgia
• When administered with a fenofibrate: Abdominal pain

• Use with caution in patients with renal and hepatic impairment
• Perform LFTs at initiation of therapy with a statin

Adverse Reactions

• CV effects (peripheral edema, atrial fibrillation, atrial flutter); GI effects (constipation, abdominal distress); Musculoskeletal effects (arthralgia, musculoskeletal pain, limb pain): Other effects (hemorrhage, gout, oropharyngeal pain, increased serum TG)

Special Instructions

• Must be taken with meals
• Use with caution in patients with coagulopathy, known allergy or sensitivity to fish or shellfish

Adverse Reactions

• GI effects (diarrhea, nausea/vomiting, dyspepsia, abdominal pain, hepatotoxicity); Other effects (chest pain, decreased weight, infections)

Special Instructions

• Contraindicated in patients taking CYP3A4 inhibitors and with moderate-severe hepatic impairment or active liver disease
• May reduce absorption of fat-soluble vitamins and serum fatty acids
• Take at least 2 hours after evening meal

• Musculoskeletal effects (myalgia, arthralgia, muscle cramps); GI effects (nausea, abdominal pain, constipation); Other effects (rash, headache, dizziness)
• Myopathy has occurred and is usually associated with high dose, when statin is combined with Nicotinic acid or fibrate, in patients with renal or hepatic impairment, serious infections, hypothyroidism and advanced age
  • Rarely has rhabdomyolysis occurred
  • Advise patient to consult physician immediately if signs of muscle pain suggesting myopathy occur (especially if accompanied by fever and malaise)

• Dose should be based upon the individual’s lipoprotein profile and adjusted based on concomitant medications
• Increases in dose should be done at ≥4-week intervals based upon patient’s response until desired lipoprotein level is reached
• Should not be used in patients with active liver disease and in those with unexplained transaminase elevations
• Use with caution in patients with renal impairment as the risk of myopathy is increased
• Liver function should be tested before or after 6-12 weeks of therapy and with any dose increase
• Simvastatin: Due to increased risk of myopathy, including rhabdomyolysis, use of 80 mg dose of Simvastatin should be restricted to patients who have been taking this dose chronically (≥12 months) without evidence of muscle toxicity

• GI effects (diarrhea, vomiting, abdominal cramping); Other effects (myalgia, rashes, alopecia)
• Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported

• Avoid in patients with pre-existing blood dyscrasias, renal failure, severe hepatic impairment; concomitant use of strong CYP3A4 inhibitors or P-gp inhibitors
• Consider temporary interruption or discontinuation of treatment if neuromuscular toxicity or rhabdomyolysis develops

• GI effects (reflux, fish odor or taste, nausea/vomiting, diarrhea, constipation); rarely eczema and acne
• Moderate elevation of transaminases have been reported in patients with hypertriglyceridemia

• Due to moderate increase in bleeding time (with high dosage), patients on anticoagulant therapy must be monitored and dosage of anticoagulant adjusted as necessary