Xylazine Hydrochloride: what the FDA reviewed for dog products

Anased® NADA 139-236, Supplemental approval, April 24, 1990; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs; foi_id 452; FDA PDF

Indication

Sedation with a shorter period of analgesia in dogs (diagnostic, orthopedic, dental and minor surgical procedures, restraint of fractious animals, preanesthetic and with local anesthetics).

Dose regimen

Intravenous 0.5 mg/lb (1.1 mg/kg); intramuscular or subcutaneous 1.0 mg/lb (2.2 mg/kg), Intravenous, intramuscular or subcutaneous, Single dose, 20 mg/mL solution; in large dogs (over 50 lb) 0.5 mg/lb IM may provide sufficient sedation and/or analgesia (summary text reads '0.5 mg/kg (1.1 mg/kg)')

Intravenous 0.5 mg/20 lb body weight (0.5 mg/lb, or 1.1 mg/kg) intramuscular or subcutaneous 1.0 mg/20 lb body weight (1.0 mg/lb, or 2.2 mg/kg).

Target-animal safety

dose multiples 0x (placebo), 1x (0.50 mg/lb), 2x (1.00 mg/lb), 4x (2.00 mg/lb); duration Single intravenous dose; each dog observed for at least 4 weeks; serum biochemistry and hematology at -(3 to 7), 0, +2 and +7 days; necropsy/histopathology on 8 dogs; animals 12 female and 12 male healthy adult mixed breed dogs (four groups).

a. Purpose of the study: The study was designed to test the safety of AnaSed(TM), Xylazine Injection, 20 mg/ml in dogs treated at 0 (control), 1x, 2x and 4x the normal dose. b. Test animals: 12 female and 12 male healthy adult mixed breed dogs, which were randomly assigned to four test groups.

Effectiveness

Controlled clinical field trial at three sites (Urbana IL, Nashville TN, Houston TX): double-blind comparison of AnaSed(TM) with Rompun® (active control) given IV, IM or SC; sedation measured as recumbency, arousal and walk times and analgesia as needle-prick response (baseline-corrected). Supported by a laboratory dose-titration study in 30 dogs (0.25-2.0 mg/lb IV).; n = 182; primary endpoint: Sedation times (recumbency, arousal, walk) and analgesia (needle prick response) compared with Rompun®; result: No significant differences between AnaSed and Rompun for either analgesia or sedation measures; responses to AnaSed were satisfactory. Laboratory titration: minimum reliable dose 0.50 mg/lb IV giving about 30 minutes of sedation and analgesia for 5 to 35 minutes.

Rompun® and AnaSed(TM) were tested in a double blind study in 182 dogs of both sexes. Sedation was tested by observing recumbency time, arousal time, and walk time as in the laboratory study. Analgesia was tested by observing response to a needle prick. The xylazine products were administered by IV, IM or SC injection.

Extraction notes: Supplement adding dogs as a species to NADA 139-236 (1990); contains original laboratory and field studies. No adverse-reaction table for the field trial; laboratory safety findings are recorded under target_animal_safety. The dose-titration laboratory study used 30 dogs in 5 groups of 6 (0x, 0.5x, 1.0x, 2.0x, 4.0x IV); the toxicology study used groups 1, 3, 4 and 5 (24 dogs). The dosage regimen text says '0.5 mg/20 lb' and '1.0 mg/20 lb' (apparently mL) and '0.5 mg/kg (1.1 mg/kg)' for large dogs; quoted verbatim. Ten literature abstracts are summarized as corroborative effectiveness and five as corroborative safety.

Anased® NADA 139-236, Supplemental approval, February 10, 2003; sponsor Cronus Pharma Specialities India Private Ltd.; species: Fallow Deer, Mule Deer, Sika Deer, White-tailed Deer, and Elk/Cervidae; foi_id 455; FDA PDF

Indication

Sedation accompanied by a shorter period of analgesia in Cervidae (fallow, mule, sika and white-tailed deer and elk): to calm and facilitate handling of fractious animals, diagnostic procedures, minor surgical procedures, therapeutic sedation and pain relief after injury or surgery, and as a preanesthetic to local anesthetic

Dose regimen

Fallow deer 2.0 to 4.0 mg/lb (4.4 to 8.8 mg/kg); mule, sika and white-tailed deer 1.0 to 2.0 mg/lb (2.2 to 4.4 mg/kg); elk 0.25 to 0.5 mg/lb (0.55-1.1 mg/kg), Intramuscular, Not stated in summary, Injectable 300 mg/mL sterile solution; may be used in conjunction with local anesthetics such as procaine or lidocaine

Fallow Deer (Dama dama) - 0.67 to 1.33 mL/100 lbs body weight (2.0 to 4.0 mg/lb or 4.4 to 8.8 mg/kg); M ule (Odocoileus hemionus), Sika (Cervus nippon) & White-tailed (Odocoileus virginianus) Deer - 0.33 to 0.67 mL/100 lbs body weight (1.0 to 2.0 mg/lb or 2.2 to 4.4 mg/kg); Elk (Cervus canadensis) - 0.08 to 0.17 mL/100 lbs Bodyweight (0.25 to 0.5 mg/lb or 0.55-1.1 mg/kg)

Effectiveness

No new study. Supplemental approval (Category II change) adding a 300 mg/mL concentration; effectiveness rests on the formulation being identical to the approved AnaSed 100 mg/mL solution (same active and inactive ingredients, same pH); result: No additional effectiveness studies were required for approval of the 300 mg/mL product

Based on the formulation characteristics of the proposed xylazine product, no additional effectiveness studies were required for approval of the xylazine 300 mg/mL product.

Extraction notes: NOT a dog summary: species are fallow, mule, sika and white-tailed deer and elk (Cervidae). Supplemental NADA (Category II change) providing a 300 mg/mL xylazine concentration in addition to the approved 100 mg/mL; the summary is catalogued under Anased® but the document names the product Cervizine 300 Injectable (sponsor at approval: Lloyd, Inc.). No effectiveness, target animal safety, PK or adverse-reaction studies are reported; the summary states that no additional studies were required because the 300 mg/mL and 100 mg/mL solutions contain the same active and inactive ingredients buffered to the same pH. target_animal_safety left null for that reason. Dosing frequency is not stated. The dose quote preserves a PDF-extraction typo ('M ule').

Chanazine® NADA 200-184, Original approval, July 12, 1996; sponsor Chanelle Pharmaceuticals Manufacturing Ltd.; species: Dogs and cats; foi_id 1442; FDA PDF

Indication

Sedation accompanied by a shorter period of analgesia in dogs and cats: diagnostic procedures, orthopedic procedures, dental procedures, minor surgical procedures of short duration, restraint of fractious animals, therapeutic sedation and pain relief after injury or surgery, and major surgical procedures as a preanesthetic to general anesthesia or with local anesthetics

Dose regimen

0.5 mg/lb intravenously; 1 mg/lb intramuscularly or subcutaneously (0.5 mg/lb IM may suffice in dogs over 50 lbs), Intravenous, intramuscular, or subcutaneous, Not stated in summary, Sedation usually maintained for 1 to 2 hours; analgesia lasts 15 to 30 minutes

Intravenously-0.5 mL/20 lbs body weight (0.5 mg/lb) Intramuscularly or subcutaneously-1 mL/20 lbs body weight (1 mg/lb) In large dogs (over 50 lbs), a dosage of 0.5 mg/lb administered intramuscularly may provide sufficient sedation and/or analgesia for most procedures.

Effectiveness

Generic (ANADA) approval: no in vivo study. Safety and effectiveness established by chemical equivalence to the pioneer product Rompun® 20 mg/mL Injectable (NADA 047-955); waiver from in vivo bioequivalence testing granted under the Fifth GADPTRA Policy Letter; result: Waiver from an in vivo bioequivalence study was granted June 15, 1992 because the generic and pioneer products are solutions with the same active and inactive ingredients in the same concentrations and the same pH

Based on the formulation characteristics of the generic product, Chanelle Manufacturing Pharmaceutical, Ltd. was granted a waiver June 15, 1992 (photocopy attached) from conducting an in vivo bioequivalence study with Chanazine® 20 mg/mL Injectable.

Extraction notes: Generic (ANADA 200-184) approval; the summary contains no new safety, effectiveness, PK or adverse-reaction studies. The 'effectiveness' entry records only the bioequivalence waiver / chemical-equivalence basis for approval. Species/Class is 'Dogs and cats'. Dosing frequency is not stated; the dose quote is from General Information (dosage given as mL of the 20 mg/mL solution per 20 lbs body weight).

Anased® NADA 139-236, Supplemental approval, May 16, 1995; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs and cats; foi_id 453; FDA PDF

Indication

Sedation with a shorter period of analgesia in dogs and cats (this supplement adds cats to the labeling).

Dose regimen

Intravenous 0.5 mL/20 lb body weight (0.5 mg/lb or 1.1 mg/kg); intramuscular or subcutaneous 1.0 mL/20 lb body weight (1.0 mg/lb or 2.2 mg/kg), Intravenously, intramuscularly, or subcutaneously, Single dose, 20 mg/mL solution

Intravenous - 0.5 mL/20 lb. body weight (0.5 mg/lb. or 1.1 mg/kg); Intramuscular or Subcutaneous - 1.0 mL/20 lb. body weight (1.0 mg/lb., or 2.2 mg/kg)

Effectiveness

Bioequivalence waiver (generic-type supplement); safety and effectiveness for cats based on chemical equivalence to the pioneer Rompun® 20 mg/mL (NADA 47-955); result: Waiver from an in vivo bioequivalence study granted December 17, 1991; no additional safety, efficacy or bioequivalence studies required.

Based on the formulation characteristics of the generic product, Vet-A-Mix Animal Health was granted a waiver December 17, 1991, (photocopy attached) from conducting an in vivo bioequivalence study with AnaSed® 20 mg/mL for the additional indication for use in cats.

Extraction notes: Supplement extending AnaSed 20 mg/mL labeling to cats (1995). No studies; the effectiveness entry records the bioequivalence waiver only. The summary has no Species/Class field; species_class taken from the indication ('dogs and cats'). Sponsor in summary: Lloyd, Inc. (formerly Vet-A-Mix).

Anased® NADA 139-236, Supplemental approval, May 16, 1995; sponsor Cronus Pharma Specialities India Private Ltd.; species: Fallow Deer, Mule Deer, Sika Deer, White-tailed Deer and Elk; foi_id 454; FDA PDF

Indication

Sedation with a shorter period of analgesia in fallow, mule, sika and white-tailed deer and elk (handling of fractious animals, diagnostic and minor surgical procedures, post-injury/surgery sedation, preanesthetic to local anesthetics).

Dose regimen

Fallow deer 2.0 to 4.0 mL/100 lbs (2.0 to 4.0 mg/lb); mule, sika and white-tailed deer 1.0 to 2.0 mL/100 lbs (1.0 to 2.0 mg/lb); elk 0.25 to 0.5 mL/100 lbs (0.25 to 0.5 mg/lb), Intramuscular, Single dose, 100 mg/mL solution; may be used with local anesthetics such as procaine or lidocaine

Fallow Deer (Dama dama ): 2.0 to 4.0 mL/100 lbs. body weight (2.0 to 4.0 mg/lb) Mule (Odocolieus hemionus), Sika (Cervus nippon) & White-tailed (Odocoileus virginianus) Deer: 1.0 to 2.0 mL/100 lbs. body weight (1.0 to 2.0 mg/Ib) Elk: Elk (Cervus canadensis): 0.25 to 0.5 mL/100 lbs. body weight (0.25 to 0.5 mg/lb)

Effectiveness

Bioequivalence waiver (generic-type supplement); relies on the pioneer Rompun® 100 mg/mL (NADA 47-956) safety and effectiveness data for deer and elk; result: Waiver from an in vivo bioequivalence study granted December 11, 1991 on formulation characteristics; no additional safety, efficacy or bioequivalence studies required.

Based upon the formulation characteristics of the generic product, Vet-A-Mix, Inc. (now known as Lloyd, Inc.) was granted a waiver from conducting an in vivo bioequivalence study for xylazine hydrochloride solution.

Extraction notes: This summary under a dog-listed application concerns the 100 mg/mL AnaSed product in deer and elk, not dogs; species_class recorded as stated. No studies; the effectiveness entry records the bioequivalence waiver only. The extracted dosage text contains OCR typos ('mg/Ib', 'lntramuscularly') retained verbatim in the quote.