Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders.

Abstract

Nadroparin (nadroparin calcium) is a low molecular weight heparin with a mean molecular weight of 4.5 kD. Compared with unfractionated heparin (UFH), nadroparin has a greater ratio of anti-factor Xa to anti-factor Ha activity, greater bioavailability and a longer duration of action, allowing it to be administered by subcutaneous injection for prophylaxis or treatment of thromboembolic disorders. In clinical trials conducted in older patients (mean age usually > 60 years), nadroparin was at least as effective as UFH in preventing deep vein thrombosis (DVT) and pulmonary embolism after major general or orthopaedic surgery, and in bedridden medical patients. Nadroparin was also at least as effective as dalteparin or oral acenocoumarol in preventing thromboembolic events following general and orthopaedic surgery, respectively. When used for treatment of established DVT, nadroparin was at least as effective as intravenous UFH. Subcutaneous nadroparin, at dosages similar to those used for the treatment of DVT, produced promising results in older patients with pulmonary embolism, acute ischaemic stroke or unstable angina. In 1 study, 75% of nadroparin-treated patients were able to complete their treatment at home and 36% did not require admission to hospital; the potential pharmacoeconomic implications of these results deserve further evaluation. Overall treatment costs (drug acquisition and monitoring costs) were similar for nadroparin and UFH in a French study, but nadroparin was associated with significantly less nursing time spent on treatment delivery. Nadroparin is well tolerated by older patients. The most frequently reported adverse events in a large (n approximately 4500) placebo-controlled study in general surgical patients were wound and injection site haematoma (11.8 and 10.2%, respectively, vs approximately 6.5% for placebo). When used as prophylaxis, no significant differences in bleeding complications were noted between nadroparin and UFH or acenocoumarol recipients. Prophylactic nadroparin was associated with significantly fewer withdrawals because of adverse events than UFH in elderly bedridden medical patients. When used as treatment for DVT, nadroparin was generally associated with lower occurrences of major bleeding than intravenous UFH (0.5 to 2.3% vs 2 to 5%); however, trials were not large enough to demonstrate any significant differences between the 2 agents. Similarly, the incidence of thrombocytopenia was slightly, but generally not significantly, lower in nadroparin (< 1%) than in UFH (< or = 3.5%) recipients. Thus, nadroparin should be considered an effective and well tolerated alternative to UFH for prophylaxis and treatment of DVT in older patients, with the advantage of more convenient administration and decreased monitoring requirements.