Sevoflurane: what the FDA reviewed for dog products
4 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Sevoflurane, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Petrem® (NADA/ANADA 200-438)
- SevoFlo® (NADA/ANADA 141-103)
- Sevoflurane (NADA/ANADA 200-830)
- Sevospire™ (NADA/ANADA 200-467)
Petrem® NADA 200-438, Original approval, April 03, 2008; sponsor Piramal Pharma Ltd.; species: Dogs; foi_id 1164; FDA PDF
Indication
Induction and maintenance of general anesthesia in dogs.
Dose regimen
3.7-4.0% inhaled (no premedication) or 3.3-3.6% (with premedication) for maintenance, inhalation, continuous during anesthesia, Mask induction with up to 7% sevoflurane in oxygen in the healthy dog
Maintenance: Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7-4.0% sevoflurane in oxygen in the absence of premedication and 3.3-3.6% in the presence of premedication.
Effectiveness
Bioequivalence (ANADA): waiver from in vivo bioequivalence study granted on formulation characteristics; no new safety or effectiveness data; result: Biowaiver; inhalant with the same active ingredient, concentration and dosage form as pioneer SEVOFLO (NADA 141-103, Abbott Laboratories, approved November 17, 1999)
Based on the formulation characteristics of the generic product, Minrad, Inc. was granted a waiver from the requirement of an in vivo bioequivalence study for the generic product PETREM (sevoflurane).
Extraction notes: Generic ANADA (sponsor in the summary: Minrad, Inc.; catalogue sponsor Piramal Pharma Ltd.), approved April 3, 2008, by biowaiver. No PK, target animal safety, effectiveness or adverse reaction content.
Sevoflurane NADA 200-830, Original approval, January 30, 2026; sponsor Parnell Technologies Pty. Ltd.; species: Dogs; foi_id 17972; FDA PDF
Indication
Induction and maintenance of general anesthesia in dogs.
Dose regimen
3.7 - 4.0% inhaled (no premedication) or 3.3 - 3.6% (with premedication) for maintenance, inhalation, continuous during anesthesia, Mask induction with up to 7% sevoflurane in oxygen, producing surgical anesthesia in 3 to 14 minutes
Maintenance: Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7 - 4.0% sevoflurane in oxygen in the absence of premedication and 3.3 - 3.6% in the presence of premedication.
Effectiveness
Bioequivalence (ANADA): biowaiver granted on formulation characteristics; no in vivo bioequivalence, effectiveness or target animal safety study; result: Biowaiver; liquid with the same active ingredient, concentration and dosage form as RLNAD SevoFlo (NADA 141-103, Zoetis)
Based on the formulation characteristics of the generic product, Parnell Technologies Pty. Ltd. was granted a biowaiver for the generic product Sevoflurane inhalation anesthetic.
Extraction notes: Generic ANADA (Parnell Technologies Pty. Ltd.) approved January 30, 2026 by biowaiver. The batch plan's single 'PK sentence' is the biowaiver statement about bioavailability; no PK values, target animal safety, effectiveness or adverse reaction content.
SevoFlo® NADA 141-103, Original approval, November 17, 1999; sponsor Zoetis Inc.; species: Dogs; foi_id 635; FDA PDF
Indication
Induction and maintenance of general anesthesia in dogs.
Dose regimen
3.7-4.0% inhaled (no premedication) or 3.3-3.6% (with premedication) for maintenance, inhalation (precision vaporizer calibrated for sevoflurane, in oxygen), continuous during anesthesia, Mask induction with 5 to 7% sevoflurane in oxygen, producing surgical anesthesia in 3 to 14 minutes; premedication with opioid, alpha-2 agonist, benzodiazepine or phenothiazine lowers maintenance requirements
Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7-4.0% sevoflurane in oxygen in the absence of premedication and 3.3-3.6% in the presence of premedication.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | MAC 2.36 + 0.46% (mean + SD) | Minimum alveolar concentration in 18 mongrel dogs (Kazama & Ikeda 1988), controlled ventilation, tail-clamp stimulus | Sevoflurane’s MAC equivalent of 2.36 + 0.46% (mean + standard deviation (SD) was used as the basis for further evaluation. |
| other | washout time 48 + 11 minutes (mean + SD) | Rate-of-rise/washout study in 12 dogs; isoflurane 52 + 13 min, halothane 72 + 9 min | Washout times were as follows (mean + SD): sevoflurane 48 + 11 minutes |
| clearance | approximately 45% of absorbed dose eliminated through the lungs within two hours | Pulmonary desaturation data from one dog, fluoride toxicity/metabolism study (4 mongrel dogs, 3% and 4% sevoflurane x 3 h) | Pulmonary desaturation data from one dog indicated that approximately 45% of the absorbed sevoflurane dose was eliminated through the lungs within two hours after anesthesia, confirming that most of the anesthetic dose is rapidly cleared through the lungs. |
| other | elimination essentially complete within 24 hours | 4 mongrel dogs after 3 h anesthesia | Elimination of sevoflurane from all four dogs was essentially complete within 24 hours of anesthesia. |
| cmax | 20.0 + 4.8 mcmole/L serum inorganic fluoride at 3 hours | Metabolite (inorganic fluoride) during 4% sevoflurane x 3 h, 4 mongrel dogs; fell to 11.5 + 4.8 mcmole/L by 1.3 h post-anesthesia and normal by 24 h | During anesthesia with 4% sevoflurane, m ean inorganic fluoride concentration increased during the anesthetic period to a maximum of 20.0 + 4.8 mcmole/L at 3 hours. |
| other | 18.5 mcmole/L serum inorganic fluoride | After 3 hours of 3% sevoflurane, 4 mongrel dogs; not associated with renal toxicity | The serum inorganic fluoride concentration following 3 hours of exposure to 3% sevoflurane was 18.5 mcmole/L. |
| other | HFIP glucuronide in urine approximately 2.5% of total sevoflurane uptake | Urinary excretion after 4% sevoflurane x 3 h; metabolite elimination essentially complete by 48 h | Based on the urinary excretion data for HFIP glucuronide following exposure to 4% sevoflurane, this represents approximately 2.5% of the total sevoflurane uptake. |
Target-animal safety
dose multiples 5-8% mask induction then 4-5% maintenance (approx. 1.7-2.1 MAC), 3 h/day x 10 exposures; halothane positive control; duration 3 hours/day, 5 days/week for 2 weeks (30 hours total), with epinephrine arrhythmia challenge during the tenth anesthesia and necropsy; animals 2 groups of 8 dogs.
Dogs were assigned to 2 groups of 8 dogs (4 dogs/sex) and treated with either sevoflurane or halothane. Half of the dogs were mechanically ventilated; the other half breathed spontaneously. Dogs were exposed for 3 hours/day, 5 days/week for 2 weeks, for a total of 30 hours.
| Finding | Quote |
|---|---|
| Faster, smoother mask induction than halothane; no apnea | Induction was achieved in 5 - 15 minutes with sevoflurane and 15 - 30 minutes with halothane. |
| Greater respiratory depression than halothane | Respiration was depressed to a greater extent by sevoflurane (3 to 28 respirations/minute) than by halothane (4 to 54 respirations/minute). |
| Less cardiac sensitization to epinephrine than halothane (no ventricular fibrillation; PVC runs in 5/8) | None of the dogs receiving sevoflurane developed ventricular fibrillation; however, 5 of 8 dogs developed runs of premature ventricular contractions at epinephrine doses of 2 to 32 mcg/kg. |
| Transient ALP elevations and mild hepatocellular vacuolization in both anesthetic groups; no clinically significant clinical pathology changes | Transient elevations in ALP were noted in some dogs of both treatment groups and mild vacuolization of liver parenchymal cells were found during necropsy. |
| No renal toxicity under worst-case Compound A conditions after 30 h exposure | Under worst-case exposure conditions known to be associated with the production of Compound A (low flow rate, high moisture and temperature in the presence of soda lime), toxicity to the kidney was not observed after a total of 30 hours of sevoflurane exposure. |
| Acute toxicity study (1969, 23 mongrel dogs): 3 of 5 dogs died at 8% for 1 h; dogs survive 1-h exposure up to 6%; deaths due to respiratory depression/acidosis | Acute death during anesthesia is due to respiratory depression and acidosis. |
Effectiveness
Multi-site (3 university clinics) clinical trial in client-owned dogs (ASA I-III) undergoing elective or emergency surgical/non-surgical procedures, no separate control group (21 CFR 514.111); 6 treatment groups by premedication/induction regimen (thiopental, propofol or sevoflurane mask induction), all maintained on sevoflurane; adverse reactions systematically recorded in 128 dogs after a protocol amendment; n = 196; primary endpoint: Investigator-rated quality of induction, maintenance and recovery; induction and recovery times; physiological variables (BP, RR, pulse, temperature, SpO2, ETCO2); result: Mask induction required 4-7% (mean 4.88%) with mean time to intubation 7.3 min (5-7% preferable); mean maintenance vaporizer concentration 3.31-3.63% over the first 30 min; mean time to extubation 8.3 min; induction quality excellent/good in 183/196 and recovery excellent/good in 184/196; hypotension (<60 mm Hg) in over half of dogs was managed without morbidity; concluded safe and effective for induction and maintenance of anesthesia
Adverse reactions were consistently reported using an adverse event form in 128 of the total number of 196 dogs included in the study.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Hypotension | 72 dogs; 56.25% | hypotension 72 56.25% | |
| Tachypnea | 67 dogs; 52.34% | tachypnea 67 52.34% | |
| Muscle tenseness | 56 dogs; 43.75% | muscle tenseness 56 43.75% | |
| Excitation | 40 dogs; 31.25% | excitation 40 31.25% | |
| Apnea | 24 dogs; 18.75% | apnea 24 18.75% | |
| Emesis | 13 dogs; 10.16% | emesis 13 10.16% |
Extraction notes: 1999 original approval. Indication quote starts at 'is indicated' because the text has a private-use trademark glyph (U+F8EA) immediately after 'SevoFlo'. No formal PK study: PK entries are MAC/washout literature values and metabolite (inorganic fluoride, HFIP) data from a 4-dog metabolism study; 'm ean' in the fluoride quote is a PDF-extraction artefact copied verbatim. Adverse reaction percentages are from the uncontrolled clinical trial (denominator 128 dogs enrolled after the Nov 30, 1995 amendment; no control group). One serious adverse reaction (suspected severe hypotension) resolved with reduced concentration, controlled ventilation and IV fluids. TAS: four studies (30-hour toxicity study 1969, 16 Beagles; acute toxicity 1969, 23 + 4 mongrels with deaths at 8%; liver toxicity 1989, 12 Beagles at 1.8 MAC = 4.2% x 1 h, no changes unique to sevoflurane; fluoride toxicity 1978, 4 mongrels). Compatibility study (16 Beagles, 4x4 Latin squares) showed premedication reduced sevoflurane maintenance requirements by 18-31%; apnea was the most frequent adverse reaction. Sighthounds (n=10) showed no prolonged recovery.
Sevospire™ NADA 200-467, Original approval, November 27, 2009; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 1181; FDA PDF
Indication
Induction and maintenance of general anesthesia in dogs.
Dose regimen
3.7-4.0% inhaled (no premedication) or 3.3-3.6% (with premedication) for maintenance, inhalation, continuous during anesthesia, Mask induction with up to 7% sevoflurane in oxygen in the healthy dog
Maintenance: Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3.7-4.0% sevoflurane in oxygen in the absence of premedication and 3.3-3.6% in the presence of premedication.
Effectiveness
Bioequivalence (ANADA): waiver from in vivo bioequivalence study granted on formulation characteristics; no new safety or effectiveness data; result: Biowaiver; liquid with the same active ingredient, concentration and dosage form as pioneer SEVOFLO (NADA 141-103, Abbott Laboratories)
Based on the formulation characteristics of the generic product, Halocarbon Products Corp. was granted a waiver from the requirement for an in vivo bioequivalence study for the generic product Sevoflurane.
Extraction notes: Generic ANADA approved November 27, 2009 by biowaiver; the summary names the product simply 'Sevoflurane' (sponsor Halocarbon Products Corp.), while the catalogue lists it as Sevospire (Dechra). No PK, target animal safety, effectiveness or adverse reaction content.
Reproduce: foi_structured_search(query="Sevoflurane") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).