Atipamezole Hydrochloride: what the FDA reviewed for dog products
6 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Atipamezole Hydrochloride, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Canine; Dogs.
Products
- Antisedan® (NADA/ANADA 141-033)
- Atipamezole Hydrochloride Injection (NADA/ANADA 200-838)
- CONTRASED™ (NADA/ANADA 200-772)
- Cropamezole™ (NADA/ANADA 200-753)
- REVERTIDINE™ (NADA/ANADA 200-624)
Antisedan® NADA 141-033, Original approval, August 06, 1996; sponsor Orion Corp.; species: Dogs; foi_id 562; FDA PDF
Indication
Reversal of the clinical effects of the sedative and analgesic agent medetomidine hydrochloride (Domitor) in dogs
Dose regimen
5.0 mg per square meter body surface area after 1.0 mg per square meter IM medetomidine (5 times the medetomidine dose; same injection volume mL for mL), Intramuscular injection, single dose, at any time following Domitor administration, administered IM regardless of the route used for Domitor; concentration 5.0 mg/mL vs Domitor 1.0 mg/mL
Antisedan® is administered intramuscularly regardless of the route used for Domitor®. The concentration of Antisedan® has been formulated such that the volume of injection is the same (mL for mL) as the recommended dose volume of Domitor®, and may be given at any time following Domitor® administration. Although injection volumes are the same, the concentration of Antisedan® (5.0 mg/mL) is 5 times that of Domitor® (1.0 mg/mL).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| tmax | 0.17 hr | single 500 mcg/kg IM, radiolabeled atipamezole, 6 laboratory beagles (Study Atip 4/41) | Results and Conclusions: Atipamezole was absorbed rapidly with Tmax calculated to be 0.17 hr. |
| other | apparent distribution volume 2.5 L/kg | single 500 mcg/kg IM, 6 laboratory beagles | The apparent distribution volume was 2.5 L/kg. |
| half-life | 2.6 hr | elimination half-life, single 500 mcg/kg IM, 6 laboratory beagles | Elimination half-life was 2.6 hr. |
Target-animal safety
dose multiples 0X, 1X, 3X, 5X, 10X, medetomidine 1X + atipamezole 3X; duration 3 daily IM doses (1X, 3X, 5X, medetomidine+3X); single dose at 10X; animals Thirty-six.
Purpose: The purpose of this study was to assess the target animal safety and acute toxicity of atipamezole when administered intramuscularly to dogs. ii. Test Animals: Thirty-six male and female laboratory beagles, approximately 5 months old at study initiation, weighing from 5.3 to 7.8 kg.
| Finding | Quote |
|---|---|
| All 10X dogs showed stimulant-type signs (hyperactivity, panting, tremors, salivation, soft/liquid feces, injected sclera) | All male and female dogs in the 10X group showed one or more effects (hyperactivity, panting, tremors, salivation, soft or liquid feces, injected sclera, etc.) of stimulation. |
| Increased creatine kinase and AST at 10X | Mean creatine kinase and aspartate aminotransferase values were increased in dogs administered the 10X dose of atipamezole. |
| No effects on body weight, food consumption, hydration, physical exam or ECG | There were no atipamezole-related effects on body weight, food consumption, hydration, physical examination results, or electrocardiographic data. |
| Localized skeletal muscle degeneration/necrosis at IM injection sites in all treated dogs (considered mild, clinically insignificant) | At intramuscular injection sites, localized skeletal muscle degeneration and necrosis occurred in all dogs given atipamezole. |
| Conclusion: no life-threatening toxicity at 10X single dose or 1X/3X/5X for three days | Based on this study, the administration of atipamezole was not associated with any life threatening toxicity when given in a single dose at 10X the anticipated use rate or when given daily for three consecutive days at 1X, 3X or 5X the anticipated use rate, both without prior administration of medetomidine, and at 3X the anticipated dose rate following the administration of medetomidine. |
Effectiveness
Multicentered, randomized, blinded, placebo-controlled clinical field study (CD-0112-91; 8 investigators); atipamezole IM at five times the preceding medetomidine dose (3.75 mg/m2 after 0.75 mg/m2 IV; 5.0 mg/m2 after 1.0 mg/m2 IM); n = 233 (115 atipamezole, 118 placebo); primary endpoint: Sedation score, walking ability and heart rate at 15-minute intervals for 1 hour after reversal; clinical success = excellent/good overall reversal assessment without relapse; result: All atipamezole cases but one were clinical successes (99.1% per Table 2) vs 7 of 118 (5.9%) placebo; rates of normal sedation/walking significantly higher (p<0.001) from 15 minutes onward
Of the 233 cases which could be used to evaluate atipamezole, 115 were treated with atipamezole while 118 were treated with placebo.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Brief excitement or apprehensiveness upon reversal (rare) | Side Effects: Atipamezole side effects were infrequent and mild. Rarely, dogs exhibited brief excitement or apprehensiveness upon reversal. |
Extraction notes: Effectiveness result figures (99.1% vs 5.9%, p<0.001) come from Table 2 and the statistical analysis text of study CD-0112-91; the effectiveness quote grounds the case counts only. Dose determination (16 dogs, crossover, 0/1/5/10 mg/m2) and dose confirmation (16 dogs, 3.75 mg/m2 after IV medetomidine) studies not captured. A second TAS study (12 dogs, 3X medetomidine followed by three 1X atipamezole doses) found the regimen well tolerated. No incidence table of adverse reactions in the field study.
Antisedan® NADA 141-033, Supplemental approval, December 01, 2006; sponsor Orion Corp.; species: Canine; foi_id 563; FDA PDF
Indication
Reversal of the sedative and analgesic effects of dexmedetomidine (DEXDOMITOR) and medetomidine (DOMITOR) in dogs; supplement adds the DEXDOMITOR indication
Dose regimen
3750 mcg/m2 (after intravenous agonist) or 5000 mcg/m2 (after intramuscular agonist), Intramuscular, once (reversal), administered IM regardless of the route used for DEXDOMITOR or DOMITOR; same injection volume as the agonist dose; dosed by body surface area
The atipamezole dose for the reversal of intravenous DEXDOMITOR or DOMITOR is 3750 mcg/m2. The atipamezole dose for the reversal of intramuscular DEXDOMITOR or DOMITOR is 5000 mcg/m2.
Target-animal safety
dose multiples 3X dexmedetomidine followed by three 1X atipamezole doses; duration single 3X dexmedetomidine dose (IV or IM) then 3 sequential 1X atipamezole IM doses at 30-minute intervals; animals 3 beagle dogs/sex/group, two groups (IV and IM dexmedetomidine).
Two groups of 3 beagle dogs/sex/group were given a 3X dose of dexmedetomidine either IV or IM followed by 3 sequential 1X doses of atipamezole (ANTISEDAN), administered every 30 minutes after dexmedetomidine administration.
| Finding | Quote |
|---|---|
| Dogs stood within 4 to 18 minutes of the first atipamezole dose; sedation resolved over 90 minutes | Following the first dose of atipamezole, the animals were able to stand within 4 to 18 minutes, and sedated behaviors gradually resolved over the next 90 minutes of observation time. |
| Mild creatine kinase elevations from repeated IM injections | Mild elevations in creatine kinase were associated with repeated IM injections. |
| One dog vomited after 3X dexmedetomidine (not after atipamezole) | Adverse Reactions: One dog vomited after receiving 3X dexmedetomidine, with no reoccurrence during the 3 atipamezole injections. |
| No toxicological effects of three atipamezole reversal injections | There were no toxicological effects of administration of 3 atipamezole reversal injections. |
| Cardiorespiratory crossover study (5 beagles): sedation reversed within 5-10 minutes, no relapse | All clinical signs of sedation induced by dexmedetomidine (IV or IM) were successfully reversed within 5 to 10 minutes following atipamezole administration, and no observation of sedation relapse was observed in any dog (monitored for 3 hours). |
| No arrhythmias after dexmedetomidine plus atipamezole | No arrhythmias were observed in dogs treated with dexmedetomidine and atipamezole at any time point. |
Effectiveness
Masked, balanced, controlled, randomized, multicenter comparative field study (7 UK and 5 German clinics; Orion MPV9901); 8 parallel groups of dexmedetomidine or medetomidine IV/IM with or without atipamezole IM (3750 mcg/m2 after IV agonist, 5000 mcg/m2 after IM agonist); 213 dogs enrolled; n = 55 after DEXDOMITOR and 54 after DOMITOR (one hundred and nine evaluated with ANTISEDAN); primary endpoint: Duration and quality of reversal of sedation (posture, response to noise, jaw tone, ability to perform procedures) and analgesia (pedal reflex), plus heart rate, respiratory rate, temperature and mucous membranes, compared with non-reversed sedated dogs; result: At 15 minutes after atipamezole 95.5% (IV dexmedetomidine) and 92% (IV medetomidine), and 95.8% (IM dexmedetomidine) and 91.3% (IM medetomidine) of dogs were normal or slightly sedated and able to stand; concluded IM ANTISEDAN is effective and safe in reversing DEXDOMITOR- or DOMITOR-induced sedation and analgesia
One hundred and nine dogs were evaluated in the groups treated with ANTISEDAN (55 dogs received DEXDOMITOR, and 54 received DOMITOR). Atipamezole was administered at the completion of the procedure, within a range of 39-57 minutes after administration of either dexmedetomidine or medetomidine.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Sinus arrest (one dog, IM medetomidine group, 5 minutes after atipamezole; attributed most likely to the alpha2-agonist) | Adverse events in general were associated with the administration of alpha2-agonists, not the reversal agent. One dog treated with IM medetomidine showed 4 instances of sinus arrest at the 5 minute timepoint after atipamezole administration; all other timepoints after atipamezole reversal were negative for arrhythmias. |
Extraction notes: Supplemental approval adding the DEXDOMITOR indication; TAS data are two dexmedetomidine studies in which atipamezole was the reversal agent (WEL 00-008 with 12 dogs; CERB 20040011PCC crossover with 5 instrumented beagles). No new PK. Effectiveness result percentages are taken from the posture results text; the effectiveness quote grounds the evaluated-dog counts.
Atipamezole Hydrochloride Injection NADA 200-838, Original approval, February 06, 2026; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 18046; FDA PDF
Indication
Reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride and medetomidine hydrochloride in dogs
Dose regimen
3750 mcg/m2 (after intravenous agonist) or 5000 mcg/m2 (after intramuscular agonist), Intramuscular injection, single dose (reversal), administered IM regardless of the route used for dexmedetomidine or medetomidine; dosed by body surface area (weight-band tables)
The atipamezole dose for the reversal of intravenous (IV) dexmedetomidine hydrochloride or medetomidine hydrochloride is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine hydrochloride or medetomidine hydrochloride is 5000 mcg/m2.
Effectiveness
Generic (ANADA) approval; in vivo bioequivalence study waived based on formulation characteristics (same active ingredient, concentration and dosage form as the RLNAD ANTISEDAN, NADA 141-033); no effectiveness or target animal safety studies required; result: Biowaiver granted; product deemed safe and effective by reference to the RLNAD
was granted a biowaiver for the generic product Atipamezole Hydrochloride Injection (atipamezole hydrochloride).
Extraction notes: ANADA with bioequivalence waiver; no studies in this summary. 'effectiveness' records the biowaiver statement, not a study. RLNAD: ANTISEDAN (NADA 141-033).
REVERTIDINE™ NADA 200-624, Original approval, July 02, 2018; sponsor Modern Veterinary Therapeutics, LLC; species: Dogs; foi_id 3881; FDA PDF
Indication
Reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride and medetomidine hydrochloride in dogs
Dose regimen
3750 mcg/m2 (after intravenous agonist) or 5000 mcg/m2 (after intramuscular agonist), Intramuscular injection, single dose (reversal), administered IM regardless of the route used for dexmedetomidine or medetomidine; dosed by body surface area (weight-band tables)
REVERTIDINE™ is administered intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for dexmedetomidine or medetomidine. The atipamezole dose for the reversal of IV dexmedetomidine or medetomidine is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine or medetomidine is 5000 mcg/m2.
Effectiveness
Generic (ANADA) approval; in vivo bioequivalence study waived based on formulation characteristics (same active ingredient, concentration and dosage form as the RLNAD ANTISEDAN, NADA 141-033); no effectiveness or target animal safety studies required; result: Biowaiver granted; product deemed safe and effective by reference to the RLNAD
Based on the formulation characteristics of the generic product, Modern Veterinary Therapeutics, LLC, was granted a waiver from the requirement to perform an in vivo bioequivalence study for the generic product REVERTIDINE™ (atipamezole hydrochloride) Sterile Injectable Solution.
Extraction notes: ANADA with bioequivalence waiver; no studies in this summary. 'effectiveness' records the biowaiver statement, not a study. RLNAD: ANTISEDAN (NADA 141-033).
Cropamezole™ NADA 200-753, Original approval, July 11, 2023; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs; foi_id 14244; FDA PDF
Indication
Reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride and medetomidine hydrochloride in dogs
Dose regimen
3750 mcg/m2 (after intravenous agonist) or 5000 mcg/m2 (after intramuscular agonist), Intramuscular injection, single dose (reversal), administered IM regardless of the route used for dexmedetomidine or medetomidine; dosed by body surface area (weight-band tables)
The atipamezole dose for the reversal of intravenous dexmedetomidine hydrochloride or medetomidine hydrochloride is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine hydrochloride or medetomidine hydrochloride is 5000 mcg/m2.
Effectiveness
Generic (ANADA) approval; in vivo bioequivalence study waived based on formulation characteristics (same active ingredient, concentration and dosage form as the RLNAD ANTISEDAN, NADA 141-033); no effectiveness or target animal safety studies required; result: Biowaiver granted; product deemed safe and effective by reference to the RLNAD
Based on the formulation characteristics of the generic product, Cronus Pharma Specialities India Private Ltd., was granted a biowaiver for the generic product Cropamezole™ (atipamezole hydrochloride) sterile injectable solution.
Extraction notes: ANADA with bioequivalence waiver; no studies in this summary. 'effectiveness' records the biowaiver statement, not a study. RLNAD: ANTISEDAN (NADA 141-033).
CONTRASED™ NADA 200-772, Original approval, March 01, 2024; sponsor Parnell Technologies Pty. Ltd.; species: Dogs; foi_id 15091; FDA PDF
Indication
Reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride and medetomidine hydrochloride in dogs
Dose regimen
3750 mcg/m2 (after intravenous agonist) or 5000 mcg/m2 (after intramuscular agonist), Intramuscular injection, single dose (reversal), administered IM regardless of the route used for dexmedetomidine or medetomidine; dosed by body surface area (weight-band tables)
The atipamezole dose for the reversal of intravenous dexmedetomidine hydrochloride or medetomidine hydrochloride is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine hydrochloride or medetomidine hydrochloride is 5000 mcg/m2.
Effectiveness
Generic (ANADA) approval; in vivo bioequivalence study waived based on formulation characteristics (same active ingredient, concentration and dosage form as the RLNAD ANTISEDAN, NADA 141-033); no effectiveness or target animal safety studies required; result: Biowaiver granted; product deemed safe and effective by reference to the RLNAD
was granted a biowaiver for the generic product CONTRASED™ (atipamezole hydrochloride) sterile injectable solution.
Extraction notes: ANADA with bioequivalence waiver; no studies in this summary. 'effectiveness' records the biowaiver statement, not a study. RLNAD: ANTISEDAN (NADA 141-033).
Reproduce: foi_structured_search(query="Atipamezole Hydrochloride") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).