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Click below to see more information about NOCITA® (bupivacaine liposome injectable suspension) pharmacokinetic values and efficacy studies.

NOCITA PHARMACOKINETIC VALUES

Pharmacokinetic Values of Liposomal Bupivacaine in Relation to Levels Causing Seizure Onset in Dogs

The pharmacokinetic values for bupivacaine after a single subcutaneous administration of NOCITA or bupivacaine HCl solution relative to the bupivacaine levels that have been associated with seizure onset in dogs are shown in Figure 6.21, 30

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Pharmacokinetic Values of Liposomal Bupivacaine in Relation to Levels Causing Seizure Onset in Cats

The pharmacokinetic values for bupivacaine after a single subcutaneous administration of NOCITA or bupivacaine HCl solution relative to the bupivacaine levels that have been associated with seizure onset in cats are shown in Figure 7.21, 31

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21. NOCITA® [package insert]. Leawood, KS: Aratana Therapeutics, Inc.; 2018.

30. Feldman HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg. 1989;69(6):794-801.

31. de Jong RH, Ronfeld RA, DeRosa RA. Cardiovascular effects of convulsant and supraconvulsant doses of amide local anesthetics. Anesth Analg. 1982;61(1):3-9.

NOCITA EFFICACY STUDIES

NOCITA Efficacy Study

Canine Pivotal Field Study32

The effectiveness of NOCITA in providing prolonged postsurgical analgesia was evaluated in a multicenter, placebo-controlled, randomized, masked field study in client-owned dogs undergoing CCL stabilization surgery.

Study Design

In this study, 182 dogs were enrolled and randomized to treatment with NOCITA (n = 123) or saline (placebo, n = 59). The per-protocol population included 112 dogs treated with NOCITA and 52 dogs that received saline.

Dogs received an opioid analgesic just prior to general anesthesia and surgery. Surgical technique was at the discretion of the surgeon, and included extracapsular repair, tibial plateau–leveling osteotomy (TPLO), or tibial tuberosity advancement (TTA). Table 8 shows the number and percentage of surgical procedures by treatment group.

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Using a moving-needle injection technique, a single dose of NOCITA or saline was infiltrated into the tissue layers during surgical closure. NOCITA or saline was administered either as is or with the addition of an equal volume of sterile saline or Lactated Ringer’s solution. Pain was assessed by trained observers using the short form composite measure pain score (CMPS-SF) for up to 72 hours following surgical closure. Pain assessments were conducted prior to surgery and at 0.5, 1, 2, 4, 8, 12, 24, 30, 36, 48, 56, and 72 hours after surgery. Dogs with a CMPS-SF score ≥ 6 or that were determined to be in pain by the investigator received rescue analgesic medication and were classified as treatment failures. No further CMPS-SF pain assessments were recorded for dogs that received rescue analgesia medication. The primary variable for effectiveness was evaluated over the first 24-hour time interval.

Results

The percentage of treatment success for NOCITA was statistically significantly greater than that with saline at the first 24-hour time interval (P = 0.0322). The 24-to-48-hour and 48-to-72-hour time intervals were evaluated as secondary variables and support effective use of NOCITA for up to 72 hours of analgesia (Table 9).

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Conclusions

The results of this study demonstrated that NOCITA administered at a dose of up to 5.3 mg/kg provided effective post-operative analgesia for up to 72 hours following CCL surgery in dogs.

Feline Pivotal Field Study29

The effectiveness of NOCITA in providing prolonged postsurgical analgesia was evaluated in a multicenter, placebo-controlled, randomized, masked field study in client-owned cats undergoing bilateral forelimb onychectomy.

Study Design

In this study, 241 cats were enrolled and randomized to treatment with NOCITA (n = 120) or saline (placebo, n = 121). Cats received an opioid analgesic just prior to general anesthesia and surgery. The nerve block injection sites were shaved and a standard surgical preparation with chlorhexidine or povidone iodine was used. Prior to onychectomy, NOCITA or saline was administered as a 4-point nerve block (Figure 3B).

Pain was assessed by trained observers using a modified version of the UNESP-Botucatu Multidimensional Composite Pain Scale for up to 72 hours following extubation. Pain assessments were conducted prior to surgery, and at 0.5, 1, 2, 4, 8, 12, 24, 30, 36, 48, 56, and 72 hours post-surgery. Cats with a composite pain score ≥ 6 or that were determined by the assessor to be in pain received rescue analgesic medication and were classified as treatment failures. After receiving rescue analgesia, cats did not have further pain assessments performed. The primary variable for effectiveness was evaluated over the first 24-hour time interval.

Results

The percentage of treatment success with NOCITA was statistically significantly greater than that with saline for the first 24-hour time interval (P = 0.0252). The 0- to 48-hour and 0- to 72-hour time intervals were evaluated as secondary variables and support effective use of NOCITA for up to 72 hours of analgesia (Table 10).

Please note charts are best viewed on a larger screen or desktop.

The per-protocol populations for effectiveness varied for each pain assessment time interval because of protocol deviations affecting only 1 of the 3 time intervals for some cats.

Conclusions

The results of this study confirm that NOCITA at a dose of 5.3 mg/kg/forelimb (10.6 mg/kg/cat) administered as a peripheral nerve block provides safe and effective postoperative analgesia for up to 72 hours following onychectomy in cats.

29. NOCITA Freedom on Information Summary, Supplemental NADA 141-461, 03 AUG 2018.
32. NOCITA Freedom of Information Summary, NADA 141-461, 12 AUG 2016.

The aforementioned studies were all performed in healthy dogs and cats. Patient factors, such as cardiac, renal, or hepatic disease, may increase the incidence of adverse events. No known long-term safety issues  associated with liposome bupivacaine have been identified to date.