Posts Tagged obesity

Dalteparin Dosing in Obesity- Ceiling dose?

June 24, 2010 at 9:00 pm · Filed under Articles and Clinical Tools ·Tagged , ,

Although a relationship had been shown between peak anti-Xa activity and TBW in healthy individuals, the large trials conducted to demonstrate the effectiveness of LMWHs (fixed-dose trials and trials for treatment) did not measure anti-Xa activity. Smaller trials measuring anti-Xa activity have shown a correlation between weight and anti-Xa activity in fixed-dose regimens, but only one trial demonstrated a relationship between weight and clinical outcomes.

No trials of therapeutic dosing evaluated the relationship between weight and anti-Xa levels.

The large prospective trials included relatively few obese patients, with the reported mean total body weight ranging from 66 to 80.7 kg among the various trials.[2] The highest reported body weight at baseline was 159 kg, but the actual number of patients with baseline weight above 150 kg included in these trials was not reported. The maximum dosage of dalteparin in ACS trials was 10,000 units every 12 hours, and the maximum dosage in DVT and PE trials was 18,000 units per day.[2]

Because of the results of these trials as well as subgroup analysis finding no benefit for ACS patients treated with more than 18,000 units per day, the manufacturer of dalteparin recommends a dosage not to exceed 18,000 units per day for ACS treatment.

A prospective, open-label trial was conducted evaluating two tinzaparin doses (75 and 175 units/kg) given subcutaneously as a single dose to healthy, obese volunteers (100-160 kg); the anti-Xa activity curve was compared with that in a historical control group of nonobese patients.[7] The ranges of area under the activity-time curve and maximum anti-Xa activity were compared between the groups and were found to overlap. The authors suggested that dosing based on body weight alone, independent of the presence of obesity, was appropriate and the dose should not be capped because of body weight.

Another prospective, open-label study investigated whether or not there were significant differences in V and CL of dalteparin in obese versus normal weight patients.[12] Patients with thrombotic conditions requiring therapeutic doses of dalteparin were given a dose of 200 units/kg/day for venous thromboembolic disorders or 120 units/kg twice a day for unstable angina. Prescribers could choose to base the dose on lean body weight (LBW), adjusted body weight (AdjBW), or TBW. Two anti-Xa activity levels were drawn after the second or subsequent dose to determine V and CL in the 10 obese patients and 10 nonobese patients. The results showed that TBW and AdjBW (AdjBW = LBW + 0.4 [actual body weight – LBW]) correlated better with anti-Xa activity than did LBW, suggesting that either actual body weight, or some function of it, would be the most appropriate weight on which to base the dalteparin dosage.

Conclusion

The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients
E. Al-Yaseen, P. S. Wells*, J. Anderson*, J. Martin and M. J. Kovacs
Summary. We report a retrospective chart review of 193 obese patients who weighed more than 90 kg and who received dalteparin at or near to 200 IU kg−1 actual body weight for 5–7 days for acute venous thromboembolism with 90 day follow-up information. Of the patients, 77% had idiopathic venous thromboembolism, 16% had an underlying malignancy, and 7% had a transient risk factor. Warfarin was initiated within 2 days with a target International Normalized Ratio range of 2.0–3.0. All patients were followed for 12 weeks post diagnosis. Only two patients had a major hemorrhage, 4 and 8 weeks from diagnosis. This study supports the safety of dosing dalteparin based on actual body weight in obese patients

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