Tricumed‘s LENUS Pro pump, an implantable device approved in Europe for the long-term intravenous administration of Remodulin (treprostinil) to treat pulmonary arterial hypertension (PAH), does not maintain a steady flow rate over time, a study of refill data reports.
The analysis found flow rates lower than those specified by its manufacturer in the first three months after it is implanted, and higher than expected flow rates after three years.
This variation from the established flow rate may lead to side effects requiring hospital admission or pump exchange, suggesting that routine monitoring of flow rate and appropriate dose adjustments of Remodulin should be considered in people carrying this implantable pump.
The study, “Flow rate variance of a fully implantable pump for the delivery of intravenous treprostinil in pulmonary arterial hypertension,” was published in the journal Pulmonary Circulation.
Remodulin, developed by United Therapeutics to treat PAH, is a man-made version of the hormone prostacyclin, a natural compound that helps blood vessels relax and widen, and that prevents platelets from clumping and blocking arteries, improving blood flow.
Remodulin can be administered as an injection under the skin (subcutaneously) or into a vein (intravenously). But due to its long-term stability, it can also be given via continuous infusion using a small pump. In these cases, the medicine is injected into a reservoir within the pump, which then delivers it to the patient in a steady flow.
LENUS Pro is among the pumps approved in Europe to continuously deliver Remodulin. The device is usually implanted below the ribs, and connected to a catheter near the clavicle, through which the device is refilled every two to four weeks, depending on the pump’s size.
While LENUS Pro is expected to deliver Remodulin in a steady flow rate, the actual rate through which it delivers the medicine has not been examined in the long-term.
To assess it, researchers examined retrospective data from 315 LENUS Pro pumps implanted and refilled in Germany between September 2010 and September 2018. By measuring the amount of residual drug volume at each refill, and the intervals between refills, they were able to calculate the actual rate at which Remodulin was being delivered to each patient.
During this period, 126 pumps were refilled 2,853 times by specialized healthcare services with supervision from pulmonary hypertension expert centers. Of them, 21 pumps had capacity for 20 milliliters (mL), and 69 were 40 mL pumps. The size of the remaining 36 was unknown.
The median fixed flow rate established by the pumps’ distributor, OMT GmbH, was 1.3 mL per day. But the team found that in the first three months after implantation, the pump’s actual flow rate was, on average, 6.5% lower than the pre-established rate.
This rate steadily increased over time, being 1.2% lower than the established dose in the 12 to 15 month interval after implantation, and then 8.7% higher in the interval from 24 and 27 months, and 16.1% higher between 36 and 39 months.
While the number of patients observed after 39 months was low, results suggested that this rate continued to increase after that time, reaching a up to 42.6% difference from the established fixed dose.
Nonetheless, about 94.5% of refills were within a 10% margin of the established flow rate, and they only raised above the 7.5% margin set by the distributor after three years of implantation.
The pattern of flow rate increase was similar regardless of the pump size, the initial dose of Remodulin, and the established fixed dose of the device, researchers found.
“In conclusion, during long-term application of intravenous treprostinil via the fully implantable LENUS Pro pump, the actual flow rate differs from the distributor-specified fixed flow rate, starting below the expected rate in early months and increasing slowly but steadily above the expected rate with longer term use,” they wrote.
The team believes that differences in flow rate over time are likely a consequence of Remodulin-induced alterations in a glass capillary that regulates the constant flow. The longer the chemical substances in Remodulin are in contact with this glass capillary, the greater the alterations, and the higher the flow rate.
“Frequent assessment of the flow rate and compensatory adjustments of the treprostinil dose are therefore considered mandatory and should be performed in expert centers,” the team concluded.
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