Ethiqa XR: Product Information (Page 2 of 2)

PRECAUTIONS

Mice

The safety of Ethiqa XR has not been evaluated in pregnant, lactating, neonatal, or immune-compromised mice. As with other opioids, buprenorphine may cause sedation,decreased blood pressure, decreased heart rate, decreased gastrointestinal mobility, and respiratory depression. Use caution with concomitant administration of Ethiqa XR with drugs that cause respiratory depression. The use of paper or soft bedding for up to 3 days following administration of Ethiqa XR should be considered.

Normal mice may exhibit an obtunded response to stimuli up to 4 hours after receiving Ethiqa XR.

Buprenorphine is excreted in the feces (see Clinical Pharmacology section below). Coprophagy may lead to ingestion of buprenorphine or its metabolites by mice treated with Ethiqa XR and untreated cage mates.

Rats

The safety of Ethiqa XR has not been evaluated in pregnant, lactating, neonatal, or immune-compromised rats. As with other opioids, buprenorphine may cause sedation, decreased blood pressure, decreased heart rate, decreased gastrointestinal mobility, and respiratory depression. Use caution with concomitant administration of Ethiqa XR with drugs that cause respiratory depression.

Rats may exhibit signs of nausea including pica up to 3 days post-treatment. Rats should be maintained on paper or soft bedding to avoid ingestion of wood chip-type bedding after administration of Ethiqa XR. Pica involving wood chip-type bedding can be lethal in rats.

Buprenorphine is excreted in the feces (see Clinical Pharmacology section below). Coprophagy may lead to ingestion of buprenorphine or its metabolites by rats treated with Ethiqa XR and untreated cage mates.

ADVERSE REACTIONS

Mice

No adverse reactions were observed in 20 to 25 gram young adult male and female mice after a single subcutaneous injection of Ethiqa XR at a dose 5 times the indicated dose. Laboratory parameters evaluated in the study included hematology and clinical chemistry; histopathology was also performed. In a second study, adult male and female mice received Ethiqa XR subcutaneously at 5 times the indicated dose for three doses at four day intervals. A surgical procedure was performed on the study mice prior to receiving each of the three doses of Ethiqa XR.

Mortality was seen in two male mice after the third surgical procedure and dose of Ethiqa XR (total dose of 49 mg buprenorphine/kg body weight in 8 days).

Weight loss has been observed in mice treated post-procedurally with Ethiqa XR.

Rats

Adverse reactions were evaluated in 180 to 200 gram young adult male and female rats after a single injection of Ethiqa XR. A surgical procedure was performed on the rats prior to administration of a single dose at the intended dose of 0.65 mg/kg or a single dose of 2, 6 or 10-fold excess dose. Adverse reactions also were evaluated in male and female rats administered 2, 6 and 10 times the intended dose for three doses at four day intervals.

A surgical procedure was performed on the rats prior to administration of the first of three doses. Laboratory parameters evaluated in the study included hematology, clinical chemistry, urinalysis, histopathology, and bodyweight.

Signs of nausea were observed at all dose levels within 24 hours of the dose. Signs included self-licking, self-gnawing and efforts to eat wood-chip bedding.

Mortality was seen in 1 of 36 rats exposed to wood chip bedding. Necropsy revealed the stomach and esophagus were compacted with bedding, the bladder was abnormally distended and the urine contained blood.

Mortality was seen in 3 of 222 rats treated with Ethiqa XR due to technical complications with serial bleeding of the jugular vein.

For technical assistance, or to report an adverse drug reaction, please call Fidelis Pharmaceuticals LLC at 1-833-384-4729.

For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/AnimalVeterinary/SafetyHealth.

CLINICAL PHARMACOLOGY3

Buprenorphine can act as an agonist and antagonist at different classes of opioid receptors. Agonism at the mu opioid receptor and, in some cases, antagonism at the kappa or delta opioid receptors are possible underlying mechanisms for the ceiling effect and bell-shaped dose-response curve of buprenorphine. Studies with knockout mice have shown that the antinociceptive effect of buprenorphine, which is mediated primarily by the mu opioid receptor, is attenuated by the ability of the drug to activate the opioid receptor like (ORL-1) receptor. The drug can be described as a ‘full’ and a ‘partial’ agonist at the same receptor depending on the specific assay. There appears to be no ceiling effect for analgesia, but there is a ceiling effect for respiratory depression.

Pharmacokinetic studies with bolus injections of buprenorphine in mice and rats provide similar models. After bolus intravenous administration, plasma levels decline tri-exponentially. The drug is n-deakylated in the liver to norbuprenorphine (NBN), an active metabolite. Studies have shown that glucuronide metabolites of buprenorphine and NBN are also metabolically active, and can approximate or exceed the concentration of the parent drug. Un-metabolized drug excreted in the urine and feces one week after injection was 1.9 and 22.4% of the dose, respectively, and 92% of the dose was accounted for in one week.3

Mice

Pharmacokinetic parameters of Ethiqa XR were studied in 6-8 week old male and female Balb/c mice following a single subcutaneous injection of 3.25 mg/kg bodyweight. Clinically significant blood levels were observed up to 72 hours after subcutaneous injection.

Rats

Pharmacokinetic parameters of Ethiqa XR were studied in 8 week old male and female Fischer rats following a single subcutaneous injection of 0.65 mg/kg bodyweight. Clinically significant blood levels were observed up to 72 hours after subcutaneous injection.

HOW SUPPLIED

Ethiqa XRis supplied in a multi-use glass vial containing 3.0 mL of injectable drug suspension.

Ethiqa XR 3 mL vial NDC 86084-100-30

U.S. Patent No. 8,461,173

STORAGE INFORMATION


Store between 15° and 25°C (59° – 77°F) or refrigerated. DO NOT FREEZE. If stored refrigerated, bring to room temperature before use. Once broached, the multi-dose vial should be discarded after 28 days.

REFERENCES


1. Mishra et al., Drug Delivery and Transl. Res, 2:238-253; 2012.
2. Bethune et al., The role of drug-lipid interactions on the disposition of liposome-formulated opioid analgesics in vitro and in vivo. Anesth Analg. 93(4):928-33; 2001.
3. Guarnieri et al., Lab Animal, 41(11): 337-343; 2012.

Manufactured for:
Fidelis Pharmaceuticals LLC
675 US Highway One,
Suite B113,
North Brunswick, NJ 08902

833-384-4729

www.EthiqaXR.com

Fidelis Pharmaceuticals® and EthiqaXR® are registered trademarks of FidelisPharmaceuticals LLC, a Delaware Corporation.

Packaging

Label
(click image for full-size original)

ETHIQA XR buprenorphine hydrochloride injection, suspension, extended release
Product Information
Product Type PRESCRIPTION ANIMAL DRUG Item Code (Source) NDC:86084-100
Route of Administration SUBCUTANEOUS DEA Schedule CIII
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BUPRENORPHINE HYDROCHLORIDE (BUPRENORPHINE) BUPRENORPHINE 1.3 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
CHOLESTEROL
BENZYL ALCOHOL
GLYCERYL TRISTEARATE
MEDIUM-CHAIN TRIGLYCERIDES
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:86084-100-30 1 VIAL, MULTI-DOSE in 1 CARTON contains a VIAL, MULTI-DOSE
1 3 mL in 1 VIAL, MULTI-DOSE This package is contained within the CARTON (86084-100-30)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
legally marketed unapproved new animal drugs for minor species MIF900014 01/01/2020
Labeler — Fidelis Pharmaceuticals Llc (080839562)

Revised: 07/2020 Fidelis Pharmaceuticals Llc

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