F2F Poster 21st Lancefield International Symposium for Streptococci and Streptococcal Diseases 2022

Subcutaneous infusions of high-dose benzathine penicillin G (SCIP) is safe, tolerable and potentially suitable for less frequent dosing for rheumatic heart disease secondary prophylaxis (#150)

Joseph H Kado 1 2 , Sam Salman 1 2 3 , Thel Hla 1 2 , Stephanie Enkel 1 2 , Robert Henderson 4 , Robert Hand 2 5 , Adam Hort 6 , Julie Bennett 7 , Anneka Anderson 8 , Madhu Page-Sharp 9 , Kevin Batty 9 , Jonathan Carapetis 1 2 4 , Laurens Manning 1 2 10
  1. Medical School, University of Western Australia, Crawley, WA, Australia
  2. Telethon Kids Institute, Nedlands, WA, Australia
  3. Clinical Pharmacology and Toxicology Unit, PathWest, Perth, WA, Australia
  4. Perth Children's Hospital, Nedlands, WA, Australia
  5. Royal Perth Hospital, Perth, WA, Australia
  6. WA Country Health Service, Perth, WA, Australia
  7. University of Otago, Wellington, New Zealand
  8. University of Auckland, Auckland, New Zealand
  9. Curtin Medical School, Curtin University, Bentley, WA, Australia
  10. Fiona Stanley Hospital, Murdoch, WA, Australia

Introduction:   Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine benzylpenicillin G (BPG; 1.2 MIU [900 mg]) injections administered intramuscularly. Due to dosing frequency, pain and programmatic challenges, adherence remains suboptimal. Our team has previously demonstrated that BPG delivered subcutaneously at a standard dose is safe, tolerable and has favourable pharmacokinetics, setting the scene for improved regimens with less frequent administration.

Methods: The safety, tolerability and pharmacokinetics of subcutaneous infusions of high-dose BPG was assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2 or 10.8MIU (3, 6 and 9 times the standard dose, respectively) as a single subcutaneous infusion. Delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores and penicillin concentrations were measured for 16 weeks post dose.

Results: Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero- (44 days) and first-order (t½=12 days) absorption pharmacokinetic model. Higher BMI significantly impacted the model. In simulations, time above the conventionally accepted target concentration of 20ng/mL (0.02 µg/mL) was 57 days for 10.8MIU delivered by subcutaneous infusion every 13-weeks compared with 11 days for standard  1.2MIU intramuscular dose (i.e., 63% and 39% of the dosing interval, respectively).

Conclusion:     High dose SCIP (BPG)  is safe, has acceptable tolerability and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD.