ADVICOR (NIACIN EXTENDED‐RELEASE AND LOVASTATIN TABLETS)
Description
Advicor (niacin extended‐release and lovastatin, Kos Pharmaceuticals, Inc.) is a newly Food and Drug Administration‐approved combination medication used in addition to adjunctive treatment of primary hypercholesterolemia and mixed dyslipidemia.
Pharmacology
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The drug is a combination of two familiar medications used to treat patients with elevated low‐density lipoprotein (LDL) cholesterol and total cholesterol, low high‐density lipoprotein (HDL) cholesterol, and elevated triglycerides.
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It combines extended‐release niacin and lovastatin.
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Niacin reduces LDL cholesterol, apolipoprotein B, lipoprotein(a), triglycerides, and total cholesterol. It also increases HDL cholesterol.
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Lovastatin reduces both normal and elevated LDL cholesterol. Apolipoprotein B also falls with treatment.
Mechanism of Action
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The mechanism of action of niacin is not thoroughly understood.
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Lovastatin is a 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor that prevents the production of cholesterol.
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Lovastatin is a prodrug and needs to be hydrolyzed to its active metabolite, lovastatin acid.
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The mechanism of action of LDL reduction involves the reduction of very LDL cholesterol and induction of the LDL receptor, which leads to reduction of the production or increased catabolism of LDL cholesterol.
Pharmacokinetics
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Following a single dose of the drug, peak plasma niacin and lovastatin levels were obtained in 5 hours and 2 hours, respectively.
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The extent of absorption of niacin was increased with food.
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Lovastatin is incompletely absorbed and has considerable interindividual variability.
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Grapefruit juice increases the absorption by at least 30%.
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Niacin undergoes first‐pass metabolism and is excreted in the urine.
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Niacin concentrations are higher in women than in men.
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Lovastatin also undergoes first‐pass metabolism by the cytochrome P450 3A4 system and is excreted in the urine and bile.
Warnings and Precautions
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The drug can cause significant liver dysfunction; therefore, careful monitoring of hepatic function must be performed.
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The drug should not be substituted for equivalent doses of immediate‐release niacin.
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The drug should be used very cautiously in patients with substantial alcohol consumption or a history of liver disease.
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Liver function tests should be performed on all patients at the beginning of therapy and every 6—12 weeks for at least 6 months, then periodically.
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The drug should be stopped if liver function values are three times the upper limits of normal.
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Rhabdomyolysis has been reported in patients with and without renal insufficiency.
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Periodic creatine phosphokinase determinations May be considered in patients suspected of developing rhabdomyolysis.
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The drug should be stopped if rhabdomyolysis is suspected.
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The use of the drug with cyclosporine or fibrates should be avoided.
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The drug should be stopped before giving azole antifungal agents and macrolides.
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Aspirin May decrease the metabolic clearance of niacin.
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Niacin May potentiate the effects of ganglionic blocking drugs, causing postural hypotension.
Adverse Reactions
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The most common adverse reaction is flushing (53%‐83%).
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The incidence of flushing can be reduced by pretreatment with aspirin or another nonsteroidal anti‐inflammatory drug 1/2 hour prior to taking the drug.
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Other adverse reactions include infection (20%), headache (9%), nausea (7%), and pruritus (7%).
Dosage and Administration
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The usual starting dose is 500 mg niacin extended‐release and 20 mg lovastatin.
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The drug should be taken at bedtime with a low‐fat snack.
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The tablet should not be broken, crushed, or split.
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Dosing can be increased at 4‐week intervals until the desired result is achieved.
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The maximal dosage of the drug is 1000 mg niacin extended‐release and 20 mg lovastatin.
Summary
Advicor is a new combination drug consisting of niacin extended‐release and lovastatin. It should be used to adjunctively treat patients with primary hypercholesterolemia and mixed dyslipidemia.
ARIXTRA (FONDAPARINUX SODIUM) INJECTION
Description
Arixtra (fondaparinux sodium, Sanofi‐Synthelabo, Inc.) is a newly approved, unique synthetic drug used to prevent deep venous thrombosis in patients undergoing hip fracture surgery, hip replacement surgery, and knee replacement surgery.
Mechanism of Action
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Arixtra is the first and only drug to selectively inhibit factor Xa.
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The drug selectively binds to antithrombin III, causing neutralization of factor Xa.
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This inhibits thrombin formation and thrombus development.
Pharmacokinetics
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Following subcutaneous injection, the drug is rapidly absorbed.
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Peak steady state is achieved in about 3 hours.
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Most of the drug is excreted unchanged in the urine, with an elimination half‐life of 17—21 hours.
Warnings and Precautions
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Elimination is prolonged in patients with renal insufficiency.
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Total clearance is 25% reduced in patients with mild renal impairment, 40% reduced in patients with moderate renal impairment, and 55% reduced in patients with severe renal impairment.
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Patients who weigh less than 110 lb are more likely to develop bleeding.
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Patients over 75 years of age are more likely to develop bleeding complications.
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As with other antithrombotics, the risk of developing spinal/epidural hematomas is increased in patients undergoing epidural/spinal anesthesia.
Adverse Reactions and Side Effects
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The most common adverse reaction is bleeding (2.7%).
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Asymptomatic elevation in transaminases has been reported.
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Mild local irritation has been reported.
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Other adverse reactions were anemia (19.6%), fever (13.6%), and nausea (11.3%).
Dosage and Administration
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The drug is provided in single‐dose, prefilled syringes with an automatic needle protection system.
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The recommended dose is 2.5 mg subcutaneously once a day, with the initial dose given 6—8 hours after surgery.
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The duration of therapy is 5—9 days.
Summary
Arixtra (fondaparinux sodium) is a unique new antithrombotic agent approved for the prevention of deep venous thrombosis following surgery. It is safe and simple to administer, with once‐a‐day dosing. Care must be taken with patients who weigh less than 110 lb, elderly individuals, and patients with renal insufficiency.