Overdose : מינון יתר

12      OVERDOSAGE

Clinical Presentation
The manifestations of acute buprenorphine overdose include pinpoint pupils, sedation, hypotension, hypoglycemia, respiratory depression, and death.
Treatment of Overdose
In the event of overdose, the respiratory and cardiac status of the patient should be monitored carefully. When respiratory or cardiac functions are depressed, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluids, vasopressors, and other supportive measures should be considered as indicated. Naloxone may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary.
Clinicians should consider the potential role and contribution of buprenorphine, other opioids, and other CNS depressant drugs in a patient’s clinical presentation. Clinical data are limited with regards to the possible surgical removal of the depot. Two cases of surgical removal were reported in premarketing clinical studies.
13      DESCRIPTION

SUBLOCADE (buprenorphine extended-release) injection is a clear, viscous, colorless to amber, sterile solution for subcutaneous injection only. It is designed to deliver buprenorphine at a controlled rate over a one month period.
The active ingredient in SUBLOCADE is buprenorphine free base, a mu-opioid receptor partial agonist and a kappa-opioid receptor antagonist.
Buprenorphine is dissolved in the ATRIGEL® delivery system at 18% by weight.
The ATRIGEL® delivery system is a biodegradable 50:50 poly(DL-lactide-co-glycolide) polymer and a biocompatible solvent, N-methyl-2-pyrrolidone (NMP).
SUBLOCADE is provided in dosage strengths of 100 mg and 300 mg. Table 5 presents the delivered amounts of the raw materials and the approximate delivered volume for the two dosage strengths.
Table 5. Amounts of Raw Materials and Delivered Volume for the Dosage Strengths Raw Materials in SUBLOCADE                   100 mg Dosage               300 mg Dosage Buprenorphine                                          100 mg                      300 mg Poly(DL-lactide-co-glycolide)                          178 mg                       533 mg N-methyl-2-pyrrolidone                                 278 mg                       833 mg Nominal delivered mass                                 556 mg                      1667 mg Approximate Delivered Volume                            0.5 mL                      1.5 mL The molecular weight of buprenorphine free base is 467.6, and its molecular formula is C29H41NO4.
Chemically, buprenorphine is (2S)-2-[17-(Cyclopropylmethyl)-4,5α-epoxy-3-hydroxy-6-methoxy-6α,14- ethano-14α-morphinan-7α-yl]-3,3-dimethylbutan-2-ol. The structural formula is: 
HO


O
N

CH3O
CH3
HO
C(CH3) 3