Breaking drug tablets in half is a common practice. Since our last article on this subject, some new data have become available.

The injectable direct thrombin inhibitor desirudin (Iprivask – Canyon), a recombinant analog of hirudin, the leech anticoagulant protein, was approved by the FDA in 2003 for prevention of venous thromboembolism (VTE) after elective hip arthroplasty, but was only marketed recently in the US. It has been available in Europe as Revasc for about 10 years. Two other hirudin analogs are available in the US: lepirudin (Refludan) for treatment of heparin-induced thrombocytopenia (HIT) and bivalirudin (Angiomax) for use in percutaneous coronary intervention (PCI).

View the Comparison Table: Some Parenteral Anticoagulants for VTE

The FDA has approved mipomersen (Kynamro – Genzyme) and lomitapide (Juxtapid – Aegerion), each in addition to a low-fat diet and other lipid-lowering medications, to reduce cholesterol levels in patients with homozygous familial hypercholesterolemia (HoFH).

Clopidogrel bisulfate (Plavix - Bristol-Myers Squibb/Sanofi), a new thienopyridine antiplatelet agent similar to ticlopidine (Ticlid - Medical Letter, 34:65, 1992), has been approved by the US Food and Drug Administration (FDA) for secondary prevention of myocardial infarction, stroke and other vascular events.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Tinzaparin sodium, a low molecular weight heparin, has been approved by the FDA for treatment of acute deep vein thrombosis.

Selective COX-2 Inhibitors and Bleeding Risk: An Additional Note - The Medical Letter article on Drugs for Pain (August 21, 2000) stated that the selective COX-2 inhibitors celecoxib (Celebrex) and rofecoxib (Vioxx) do not inhibit platelet aggregation or bleeding time. Perhaps we should have added, as we did in discussing use of these drugs in rheumatoid arthritis (July 10, 2000), that both celecoxib and rofecoxib, if given with warfarin (Coumadin, and others), increase INR and prothrombin time values and may increase the risk of bleeding.

Ardeparin sodium (Normiflo - Wyeth-Ayerst), a low-molecular-weight heparin, and danaparoid sodium (Orgaran - Organon), a heparinoid, have been approved by the FDA for prevention of deep vein thrombosis. Without anticoagulation, deep vein thrombosis occurs in up to 30% of patients after abdominal surgery, and in 40% to 70% of patients after major orthopedic operations on the lower limbs. Danaparoid sodium is approved in the USA only for use in hip replacement. Ardeparin is approved here only for use in knee replacement.

Coenzyme Q10, a fat-soluble antioxidant also known as ubidecarenone, ubiquinone and CoQ10, is marketed as a dietary supplement in the US, both as a single ingredient and in various combination products.