ANIMALGESICS FOR MICE- buprenorphine hydrochloride injection, suspension, extended release

Animalgesics for Mice by

Drug Labeling and Warnings

Animalgesics for Mice by is a Animal medication manufactured, distributed, or labeled by ANIMALGESIC LABORATORIES, INC., Noramco, Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

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CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

NOT APPROVED BY FDA – Legally Marketed as an FDA Indexed Product under MIF 900-014.
Extra-label Use is Prohibited.

Note – In order to be legally marketed, an animal drug product intended for a minor species must be Approved, Conditionally Approved, or Indexed by the FDA. THIS PRODUCT IS INDEXED.

For subcutaneous use in mice only.

This product is not to be used in animals intended for use as food for humans or food-producing animals.

ABUSE

WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE

Abuse Potential

Animalgesics for Mice contains buprenorphine, a high concentration (1.3 mg/mL) opioid agonist and Schedule III controlled substance with an abuse potential similar to other Schedule III opioids. The high concentration of Animalgesics for Mice may be a particular target for human abuse. Buprenorphine has opioid properties that in humans may lead to dependence of the morphine type. Abuse of buprenorphine may lead to low or moderate physical dependence or high psychological dependence. The risk of abuse by humans should be considered when storing, administering, and disposing of Animalgesics for Mice. Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (suicidal depression).

Because of human safety risks, this drug should be used only with veterinary supervision. Do not dispense Animalgesics for Mice.

Life-Threatening Respiratory Depression
The concentration of buprenorphine in Animalgesics for Mice is 1.3 mg/mL. Respiratory depression, including fatal cases, may occur with abuse of Animalgesics for Mice.

Animalgesics for Mice has additive CNS depressant effects when used with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Because of the potential for adverse reactions associated with accidental injection, Animalgesics for Mice should only be administered by a veterinarian or laboratory staff trained in the handling of potent opioids.

DESCRIPTION

Animalgesics for Mice is an injectable suspensionof extended-release buprenorphine. Buprenorphine hydrochloride, an opioid analgesic, is the active ingredient in Animalgesics for Mice. Lipid-bound buprenorphine hydrochloride is suspended in medium chain fatty acid triglyceride (MCT) oil. Lipids encapsulate the buprenorphine limiting diffusion which provides for larger doses and prolonged action.1,2Animalgesics for Mice has a slightly yellow to white opaque appearance. Each mL contains approximately 1.3 mg buprenorphine hydrochloride.The sterile product contains cholesterol, glycerol tristearate, and buprenorphine hydrochloride suspended in MCT oil.

Buprenorphine 

Formula C29H41NO4

INDICATIONS

Animalgesics for Mice is indicated for the control of post-procedural pain in mice.

DOSAGE AND ADMINISTRATION

The dosage of Animalgesics for Mice is a single subcutaneous injection of 0.05 mL per 20 gram mouse (3.25 mg/kg body weight). Therapeutic drug concentrations are maintained for 72 hours after the initial dose. If needed, a single repeat dose may be administered 72 hours after the initial dose.

1. Shake the vial briefly before each use to ensure uniform suspension.
2. Use aseptic techniques to withdraw the dose into a disposable 0.5 or 1.0 mL syringe. A 20 or 21 gauge needle should be used for injections due to the viscosity of the drug suspension.
3. Secure the mouse in a scruff-of-the-neck hold. Insert the needle into the dorsal subcutaneous space created by the scruff hold. Inject the entire dose into the dorsal subcutaneous space. An oily sheen may be observed in the dorsal fur of the mouse after injection due to leakage of the oil-based drug suspension from the injection site. The oily sheen may last for 4 to 5 days post-injection. Leakage from the injection site can be minimized by slowly injecting Animalgesics for Mice in to the subcutaneous space. The mouse can be returned to its cage immediately after receiving Animalgesics for Mice.
4. Do not return any unused drug suspension from the syringe back into the vial.
5. Once the vial is broached, Animalgesics for Mice can be stored at 15° to 25° C (59° – 77° F) for 28 days

CONTRAINDICATIONS

Only administer Animalgesics for Mice by subcutaneous injection. Animalgesics for Mice is not intended for intravenous, intra-arterial, intrathecal, intramuscular, or intra-peritoneal injection.

HUMAN SAFETY WARNINGS

Not for use in humans. Keep out of the reach of children.

Adult Human User Safety while handling Animalgesics for Mice in the laboratory:

Two trained staff for administration:Animalgesics for Mice should only be handled and administered to mice by laboratory staff trained in the handling of potent opioids. To prevent human adverse reactions or abuse, at least 2 trained administrators should be present during injection of Animalgesics for Mice.

Protective covering:To prevent direct contact of Animalgesics for Mice with human skin or mucousmembranes when handling the suspension, protective clothing is recommended.

Mucous membrane or eye contact during administration:Direct contact of Animalgesics for Mice with the eyes, oral or other mucous membranes of humans could result in absorption of buprenorphine and the potential for adverse reactions. If accidental eye, oral or other mucous membrane contact is made during administration, flush the area with water and contact a physician.

Skin contact during administration:If human skin is accidentally exposed to Animalgesics for Mice, wash the exposed area with soap and water and contact a physician. Accidental exposure could result in absorption of buprenorphine and the potential for adverse reactions.

Drug Abuse, Addiction, and Diversion of Opioids:

Controlled Substance: Animalgesics for Mice contains buprenorphine, a mu opioid partial agonist and Schedule III controlled substance with an abuse potential similar to other Schedule III opioids. Animalgesics for Mice can be abused and is subject to misuse, abuse, addiction, and criminal diversion. Animalgesics for Mice should be handled appropriately to minimize the risk of diversion, including restriction of access, the use of accounting procedures, and proper disposal methods, as appropriate to the laboratory setting and as required by law.

Abuse: Abuse of Animalgesics for Mice poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol and other substances including other opioids and benzodiazepines. Buprenorphine has been diverted for non-medical use into illicit channels of distribution. All people handling opioids require careful monitoring for signs of abuse. Drug abuse is the intentional non-therapeutic use of a prescription drug for its rewarding psychological or physiological effects. Abuse of opioids can occur in the absence of true addiction.

Storage and Discard: Animalgesics for Mice is a Class III opioid. Store in a locked, substantially constructed cabinet according to DEA and local controlled substance guidelines. Discard broached vials after 28 days. Any unused or expired vials must be destroyed by a DEA registered reverse distributor; for further information, call 1-855-406-7660.

Physician information: Animalgesics for Mice injectable suspensionis a mu opioid partial agonist(1.3 mg buprenorphine/mL). In the case of an emergency, provide the physician with the package insert. Naloxone may not be effective in reversing respiratory depression produced by buprenorphine. The onset of naloxone effect may be delayed by 30 minutes or more. Doxapram hydrochloride has also been used as a respiratory stimulant.

PRECAUTIONS

The safety of Animalgesics for Mice 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 Animalgesics for Mice with drugs that cause respiratory depression or in mice with pre-existing respiratory deficiencies.

Normal mice may exhibit an obtunded response to stimuli up to 4 hours after receiving Animalgesics for Mice.

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 Animalgesics for Mice and untreated cage mates.

ADVERSE REACTIONS

No adverse reactions were observed in 20 to 25 gram young adult male and female mice after a single subcutaneous injection of Animalgesics for Mice 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 Animalgesics for Mice 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 Animalgesics for Mice. Mortality was seen in two male mice after the third surgical procedure and dose of Animalgesics for Mice (total dose of 49 mg buprenorphine/kg body weight in 8 days).

Weight loss has been observed in mice treated post-procedurally with Animalgesics for Mice.

For technical assistance, or to report an adverse drug reaction, please call AnimalgesicLaboratories at 1-855-406-7660.

Adverse drug reactions may also be reported to the FDA/CVM at 1-888-FDA-VETS or http://www.fda.gov/AnimalVeterinary/SafetyHealth.

CLINICAL PHARMACOLOGY

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

Pharmacokinetic parameters of Animalgesics for Mice 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.

STORAGE INFORMATION

Store between 15° and 25° C (59° – 77° F). 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. Bethuneet al., The role of drug-lipid interactions on the disposition of liposome-formulated opioid analgesics in vitro and in vivo.AnesthAnalg. 93(4):928-33; 2001.
3. Guarnieri et al, Lab Animal, 41(11): 337-343; 2012.

HOW SUPPLIED

Animalgesics for Mice is supplied in a multi-use glass vial containing 3.0 mL of injectable drug suspension. One vial is capable of administering fifty 0.05 mL doses for mice. A single 0.05 mL dose of the injectable suspension contains approximately 0.065 mg buprenorphine hydrochloride.

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

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Manufactured for:

Animalgesic Laboratories
1121 Benfield Road, Suite Q
Millersville MD 21108

1-855-406-7660
www.animalgesiclabs.com

Animalgesics® is a registered trademark of AnimalgesicLaboratories, a Maryland Corporation.
February 2014

Packaging

INGREDIENTS AND APPEARANCE

ANIMALGESICS FOR MICE 
buprenorphine hydrochloride injection, suspension, extended release

Product Information
Product Type	PRESCRIPTION ANIMAL DRUG	Item Code (Source)	NDC: 86004-100
Route of Administration	SUBCUTANEOUS	DEA Schedule	CIII

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
BUPRENORPHINE HYDROCHLORIDE (UNII: 56W8MW3EN1) (BUPRENORPHINE - UNII:40D3SCR4GZ)	BUPRENORPHINE	1 mg  in 1 mL

Inactive Ingredients
Ingredient Name	Strength
CHOLESTEROL (UNII: 97C5T2UQ7J)
TRISTEARIN (UNII: P6OCJ2551R)
BENZYL ALCOHOL (UNII: LKG8494WBH)
CAPRYLIC/CAPRIC/LAURIC TRIGLYCERIDE (UNII: FJ1H6M2JG9)

Product Characteristics
Color	white (white colored, oil-based suspension in 5.0 multi-dose vial)	Score
Shape		Size
Flavor		Imprint Code
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 86004-100-30	1 in 1 CARTON
1		3.0 mL in 1 VIAL, MULTI-DOSE

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	11/01/2013

Labeler - ANIMALGESIC LABORATORIES, INC. (788213093)

Establishment
Name	Address	ID/FEI	Business Operations
Noramco, Inc.		057234486	api manufacture