Table 3.
Long-acting buprenorphine formulations
| Indication (s) | Adverse events occurring in >5% of patients | Excipients & toxicology | Delivery system | Storage and administration | |
|---|---|---|---|---|---|
| 6-month Buprenorphine Implant (Prohuphinc®) | Maintenance for patients who have achieved prolonged stability on ≤ 8mg TM buprenorphine | Headache, depression, constipation, nausea, vomiting, back pain, toothache, oropharyngeal pain and injection site reactions (pain, pruritus, & erythema) | N/A | Ethylene vinyl acetate (EVA) implants | Subdermal insertion of 4 flexible matchstick-sized rods in upper arm under local anesthetic by trained provider. |
| 11 FDA-approved productsa | |||||
| Monthly Buprenorphine Depot (Suhlocade®) | Maintenance treatment (to be used after initiation on TM buprenorphine) | Constipation, nausea, vomiting, fatigue, elevated liver enzymes, headache, and injection site reactions (pain, pruritus, & erythema) | NMP - At doses equivalent to those in the depot, reproductive harmsb were reported in animal studies. | ATIRGEL® (Tolmar Inc.) | Pre-filled syringe (refrigeration required). SC abdominal injection by trained provider. Injection volume of .5 and 1.5mL. |
| 7 FDA-approved productsc | |||||
| Weekly and Monthly Buprenorphine Depot (CAM 2038) | PROPOSED: Induction and maintenance treatment | Headache, nausea, urinary tract infection, constipation, nasopharyngitis, and injection site reactions (pain, swelling & erythema) | NMPb - dose used has a 3-fold safety margin for reproduction | FluidCyrstal® Technology (Camurus) | Pre-filled syringe (no refrigeration required) with injection volume of .16 to .64mL. SC injection into buttock by trained provider. |
| 1 FDA-approved productc | |||||
BUP— Buprenorphine, TM— Transmucosal, SC—Subcutaneous, NMP— N-methyl-2-pyrrolidase (a biocompatible solvent)
Examples of approved products with EVA: etonogestrel/ethinyl estradiol vaginal ring [NuvaRing®, Organon/Merck & Co, Kenilworth, NJ], birth control implants [Implanon®, Organon/Merck & Co. Kenilworth, NJ], and pilocarpine - ophthalmic ocular system [Ocusert® Alza Mountain View, CA]
Preimplantation losses, delayed ossification, reduced fetal weight, developmental delays and reduced cognitive function
Examples of approved products with Atrigel®: leuprolide acetate suspension for subcutaneous injection [Eligard®, Tolmar Inc. Fort Collins, CO] and doxycycline hyclate [Atridox®, Tolmar Inc. Fort Collins, CO] and doxycycline hyclate [Atridox®, Tolmar Inc. Fort Collins, CO]
NMP is present in the monthly formulation only
Oral spray for oral mucositis pain [Episil®, Camurus Lund, Sweden]