Remodulin. Advantages and Challenges

Transcription

1 Remodulin Advantages and Challenges 1

2 Remodulin Background Continuous SC* infusion Continuous SC or IV infusion Transition from Flolan (epoprostenol sodium) Based on: Phase III trials; Simonneau et al, Based on: Bioequivalence study; Laliberte et al, Based on: Phase IV transition study; Data on file 3 *SC, subcutaneous. IV, intravenous. Flolan is a registered trademark of GlaxoSmithKline. 1. Simonneau G, et al. Am J Respir Crit Care Med. 2002;165: Laliberte K, et al. J Cardiovasc 2 Pharmacol. 2004;44: Data on File, United Therapeutics Corporation.

3 Indications REMODULIN is indicated as a continuous SC or IV infusion (for those not able to tolerate a SC infusion) for the treatment of pulmonary arterial hypertension in patients with NYHA Class II IV symptoms to diminish symptoms associated with exercise. And REMODULIN is indicated to diminish the rate of clinical deterioration in patients requiring transition from Flolan; the risks and benefits of each drug should be carefully considered prior to transition. REMODULIN [package insert]. United Therapeutics Corporation;

4 IV/SC Bioequivalence Study: Log-Linear Plot of Mean Plasma Concentration 10 0 IV SC Treprostinil Concentration (ng/ml) Steady-State Hour Safety results: No significant changes in vital signs, laboratory parameters, or physical examination findings. SC adverse events were infusion-site related, headache, jaw pain, and nausea. IV adverse events were infusion-site related, headache, jaw pain, and nausea. Laliberte K, et al. J Cardiovasc Pharmacol. 2004;44:

5 Side Effect Profile Site Pain (SQ only) Extremity Pain Headache Nausea Vomiting Diarrhea Jaw Pain Rash Vasodilation 5

6 Advantages SQ No central line: less infections and less invasive Small pump Change infusions q hours IV 4 hour half-life No ice needed stable at room temp Smaller pump options Change infusions q 48 hours 6

7 Challenges SQ Site Pain Dosing IV Increased rate of central line infections More concentrated drug with smaller pumps Dosing Transitions from Flolan 7

8 Managing SQ Remodulin 8

9 Dosing SQ Remodulin Steady Titration up 2ng/kg/min/week Doses range 30-60ng/kg/min Try to keep pump rates < or =.030 Less volume, less pain 9

10 SQ Infusion Site Pain and Reaction Infusion site pain and reaction (redness and swelling) occurred in the majority of patients. Symptoms are often severe and could lead to treatment with narcotics and discontinuation of REMODULIN Infusion site pain is not related to dose Site pain varies by patient as well as by infusion site There are sometimes simply good sites and bad sites Site pain is often the worst 2 to 5 days into a new injection site 10

11 Choosing the Best SC Administration Sites Initiate therapy on abdomen, as it is easy for patients to selfadminister medication, monitor the site, and apply topical remedies Relocation sites (for increased patient comfort) include: Upper buttocks Lower flanks Back of upper arms Thighs Avoid stretch marks, scar tissue, edema, old nodular sites, bruises, and waistbands of clothes 11

12 Site Pain Care: Nonpharmacologic Approaches Encourage patients to change a bad site right away Allow patients to maintain a good site for several days Try alternative sites such as upper buttocks or back of upper arms Remove any medication droplets on the end of the needle after priming For frequent topical medication application, thin duoderm prior to catheter insertion Try dry catheter preplacement method before initiating medication Change to a more concentrated solution to allow for less volume infusion per hour 12

13 Site Pain Care: Local and Topical Approaches Ice/heat Warm bath with Epsom salt PLO gel compounds Lidoderm 5% patches (use on current or old site daytime or nighttime use) Diphenhydramine HCl, topical Aloe vera gel Triamcinolone acetonide Fluticasone proprionate nasal spray Lidocaine/prilocaine cream Hydrocortisone cream Hemorrhoid ointment 13

14 Site Pain Care: Systemic Options Ibuprofen Gabapentin Pregabalin Loratadine Hydroxyzine pamoate for severe itching Amitriptyline and other antidepressants Tramadol HCl Fexofenadine HCl or cetirizine HCl Ranitidine HCl or femotidine Pimecrolimus cream 1% or dobetasol propionate Fentanyl or other narcotics for severe pain 14

15 Important Considerations Combining multiple approaches to managing injection site pain may be helpful Dose increases should generally not be limited because of site pain Managing patients expectations up front is important in addressing site pain 15

16 Sales Tool: Pain Management Flash Card Being Finalized this week Final Layout and Printing in October Distribution to UT and Lung Rx field in October 16

17 Managing IV Remodulin Infusions 17

18 Dosing IV Remodulin Steady titration up 1-2ng/kg/min 1 2X s per week Dose ranges 30-60ng/kg/min in denovo patients transition patients seem to need higher doses Once patients get to stable dose, consider smaller pump options 18

19 Infections Aseptic Technique Absolutely no disconnects except when changing infusions Meticulous site care Prophylactic Antibiotics??? Infusion changes back to q 24 hours 19

20 Transitions Titrate Remodulin up / Titrate Flolan down Many different ways usually increments of 10% Rapid Switch Change dwell volume with Remodulin concentration Change out cassette with Remodulin Start dose is = or > than Flolan dose 20

21 Transitions -Patient Reactions What to expect? SOB Desaturations Hypotension Others? 21

22 Questions? 22