January 12, 1989
The Food and Drug Administration has notified us of a reported human exposure and adverse drug reaction at Parke Davis, Morris Plains, New Jersey to Vetalor (ketamine hydrochloride) (see attachments). Approximately, 75mg of Vetalor was accidentally squirted in the eye of veterinary assistant and within a few minutes the individual became unconscious which lasted about 10 minutes. She was treated and fully recovered after two and one-half hours but was still lethargic. No warnings or precautions were on the label to address accidental human exposure.
Compliance Officers should be aware of the hazards and related worker exposure from accidents with drugs on workers in research laboratories and related operations.
|Dept of Health and Human Services
Public Health Service
Food and Drug Admin.(HFV-210)
5600 Fisher Lane
|ADVERSE DRUG REACTION,
LACK OF EFFECTIVENESS,
PRODUCT DEFECT REPORT
(Forward to address at left)
Attach all correspondence that to this reaction.
use of this form is prohibited after April 30,1988
|Note: This report is required by law (21 CFR 510.3001). Failure to report can result in withdrawal of approval of the application.|
|1. REPORT SOURCE AND ADDRESS (mfr.distr.)
San Francisco Poison Control Center San Francisco, CA (US)
|2. DATE SENT TO FDA (Month, day, year)
|3. TYPE OF REPORT
X INITIAL follow up to report of (give date)
|4. NAME, ADDRESS AND PHONE # OF ATTENDING VETERINARIAN (In confidence)
Gary Rich, MD
Mills Hospital 100 S., San Mateo Drive
San Mateo, CA 94401
|5. NAME OR CASE IDENTIFICATION OF OWNER (In confidence)
SECTION I- DRUG DATA
|6. TRADE, NAME AND GENERIC NAME(S) OF ACTIVE INGREDIENT(S) (Include dosage form and strength. Ex. tab. 500 mg.)
Vetalar (ketamine hydrochloride injection)
|7 a. Name of Manufacturer
Parke Davis Co.
|b. NADA NO.
|8. LOT NUMBER
||9. DOSAGE REGIMEN AND ROUTE EX. 250 mg. q 12 h.p.o.)
||10. DATE(S) OF ADMINISTRATION
|11. ILLNESS/ REASON FOR USE OF THIS DRUG||12. DRUG WAS ADMINISTERED BY X VETERINARIAN, STAFF, OWNER, OTHER|
SECTION II- ANIMAL DATA
|13. NUMBER OF ANIMALS IN THIS INCIDENT||14. REACTING ANIMAL(S)|
|a. TREATED WITH DRUG||b. REACTED||c. DIED||a. SPECIES||b. BREED|
|15. CONCOMITANT MEDICAL PROBLEMS||c. AGE||d. WEIGHT||e. SEX|
|16. OVERALL STATE OF HEALTH AT TIME OF REACTION
__GOOD __ FAIR __ POOR X CRITICAL
|17. DID ANY NEW ILLNESS DEVELOP OR DID INITIAL DIAGNOSIS CHANGE AFTER SUSPECT DRUG STARTED?
X NO __ YES (explain)
|18. CONCOMITANT DRUGS ADMINISTERED|
|NAME OF DRUG||ROUTE||DOSAGE REGIMEN||DATE(S) OF ADMINISTRATION|
|FOR FDA USE ONLY|
|1._____ __D __ NAI
2._____ __PR __ AI
3._____ __PO __ AP
4._____ __R __ AL
__ I.L. __ CL __ CONT
G- HUMAN EXPOSURE, EYE(S) -9 0 SE
N- UNCONSCIOUS -9 10 Mr
G- DEPRESSION/LETHARGY -9 2 HR
*VET ASSISTANT ACCIDENTALLY SQUIRTED IN EYE
*PERSON TAKEN TO EMERGENCY ROOM
|FORM FDA 1932 (3/81)|
SECTION III- REACTION DATA
|19. DESCRIBE SUSPECTED ADVERSE REACTION: INCLUDE ALL SIGNS, RESULTS OF PERTINENT LAB TESTS, NECROPSY RESULTS. POSSIBLE CONTRIBUTING FACTORS, ETC. ALSO, INCLUDE IN THIS SECTION PRODUCT INEFFECTIVE AND PRODUCT DEFECTS SUCH AS CRACKED TABLETS, CLOUDY SOLUTION, ETC.
Unconsciousness in a veterinary assistant, due to inadvertent administration, in the eye of about 75 mg of Vetalar (ketamine). Within a few minutes of the accidental squirting, pt. remained unconscious for about 10 minutes when she was presented in ER, where, 2 1/2 hours later, had fully recovered but lethargic.
|20. ATTENDING VETERINARIAN'S LEVEL OF SUSPICION THAT DRUG CAUSED REACTION
X HIGH __MEDIUM __LOW __NO ATTENDING VET.
|21. LENGTH OF TIME BETWEEN LAST ADMINISTRATION OF SUSPECT DRUG AND ONSET OF REACTION
|22. DATE OF ONSET (mo., day. yr.)
|23. DURATION OF REACTION(Hrs.,days)
|24. WAS THE ADVERSE REACTION TREATED?
X NO __ YES(Describe treatment)
|25. OUTCOME OF REACTION DATE
__ DIED (Give date)___________
__ REMAINS UNDER TREATMENT
__ ALIVE WITH SEQUELAE
|26. WHEN REACTION APPEARED, TREATMENT SUSPECT DRUG:
X HAD ALREADY BEEN COMPLETED __CONTINUED
__DISCONTINUED DUE TO THE REACTION X STOPPED
__DISCONTINUED, REPLACED WITH ANOTHER DRUG
__DISCONTINUED, REINTRODUCED LATER
|31. NAME AND TITLE OF INDIVIDUAL RESPONSIBLE FOR ACCURACY OF REPORTED INFORMATION (Type or print)
Jan L. Worster, MD Associate Director
Worldwide Adverse Event Reporting
(Ketamine Hydrochloride Injection, USP)
Veterinary Injection For Intramuscular Use
DESCRIPTION Vetalar (ketamine hydrochloride) is a rapid-action, nonnarcotic, nonbarbiturate agent for anesthetic use in cats and for restraint in subhuman primates. It is chemically designated at 2-(o-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride and is supplied as a slightly acid (pH 35 to 55) solution for intramuscular injection in a concentration containing the equivalent of 100 mg ketamine base per milliliter and contains not more than 01 mg/ml Phemerol (benzethonium chloride) as a preservative.
ACTION Vetalar is a rapid-action agent whose pharmacological action is characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, mild cardiac stimulation and respiratory depression. Skeletal muscle tone is variable and may be normal, enhanced or diminished. The anesthetic state produced does not fit into the conventional classification of stages of anesthesia, but instead Vetalar produces a state of unconsciousness which has been termed "dissociative" anesthesia in that it appears to selectively interrupt association pathways to the brain before producing somesthetic sensory blockade. In contrast to other anesthetics, protective reflexes, such as coughing and swallowing are maintained under Vetalar anesthesia. The degree of muscle tone is dependent upon level of dose, therefore, variations in body temperature may occur. At low dosage levels there may be an increase in muscle tone and a concomitant slight increase in body temperature. However, at high dosage levels there is some diminution in muscle tone and a resultant decrease in body temperature, to the point where supplemental heat may be advisable. In cats, there is usually some transient cardiovascular stimulation, increased cardiac output with slight increase in mean systolic pressure with little or no change in total peripheral resistance. At higher doses respiratory rate is usually decreased. The assurance of a patent airway is greatly enhanced by virtue of maintained pharyngeal-laryngeal reflexes. Although some salivation is occasionally noted, the persistence of the swallowing reflex aids in minimizing the hazards associated with ptyalism. Salivation may be effectively controlled with atropine sulfate in dosages of 0.04 mg/kg (0.02 mg/lb) in cats and 0.01 to 0.05 mg/kg (0.005 to 0.025 mg/lb) in subhuman primates. Other reflexes, eg, corneal, pedal, etc., are maintained during Vetalar anesthesia, and should not be used as criteria for judging depth of anesthesia. The eyes normally remain open with the pupils dilated. It is suggested that a bland ophthalmic ointment be applied to the cornea if anesthesia is to be prolonged. Following administration of recommended doses, cats become ataxic in about 5 minutes with anesthesia usually lasting from 30 to 45 minutes at higher doses. At the lower doses, complete recovery usually occurs in 4 to 5 hours but with higher doses recovery time is more prolonged and may be as long as 24 hours. In studies involving 14 species of subhuman primates represented by a least 10 anesthesia episodes for each species, the median time to restraint ranged from 1.5 to 5.3 minutes [(Macaca nemestrina (pig-tailed macaque)] after injection. Recovery in generally smooth and uneventful. The duration is dose related. By single intramuscular injection. Vetalar usually has a wide margin of safety in cats and subhuman primates. In cats, cases of prolonged recovery and death have been reported.
INDICATIONS Vetalar may be used in cats for restraint or as the sole anesthetic agent for diagnostic or minor, brief, surgical procedures that do not require skeletal muscle relaxation. It may be used in subhuman primates for restraint.
CONTRAINDICATIONS Vetalar is contraindicated in cats and subhuman primates suffering from renal or hepatic insufficiency.
WARNINGS FOR USE IN CATS AND SUBHUMAN PRIMATES ONLY Vetalar is detoxified by the liver and excreted by the kidneys: therefore any pre-existent hepatic or renal pathology or impairment of function can be expected to result in prolonged anesthesia: related fatalities have been reported.
PRECAUTIONS In cats, doses in excess of 50 mg/kg during any single procedure should not be used. The maximum recommended dose in subhuman primates is 40 mg/kg. To reduce the incidence of emergence reactions, animals should not be stimulated by sound or handling during the recovery period. However, this does not preclude the monitoring of vital signs.
ADVERSE REACTIONS Respiratory depression may occur following administration of high doses of Vetalar. If at any time respiration becomes excessively depressed and the animal becomes cyanotic, resuscitative measures should be instituted promptly. Adequate pulmonary ventilation using either oxygen or room air is recommended as a resuscitative measure. Adverse reactions reported have included amazes, salivation, vocalization, erratic recovery and prolonged recovery, spastic jerking movements, convulsions can be controlled by ultrashort-acting barbiturates which should be given to effect. The barbiturates should be administered intravenously at a dose level of one sixth of one fourth the usual dose fro the product being used. Acepromazine may also be used. However, recent information indicates that some phenothiazine derivatives may potentiate the toxic effects of organic phosphate compounds such as found in flea collars and certain anthelmintics. A study has indicated that ketamine hydrochloride alone does not potentiate the toxic effects of organic phosphate compounds.
DOSAGE AND ADMINISTRATION Vetalar is well tolerated by cats and subhuman primates when administered by intramuscular injection. Fasting prior to induction of anesthesia or restraint with Vetalar is essential: however when preparing for elective surgery, it is advisable to withhold food for a least six hours prior to administration of Vetalar. Anesthesia may be of shorter duration in immature cats. Restraint in subhuman primates neonates (less that 24 hours of age) is difficult to achieve.
Vetalar (Ketamine Hydrochloride Injection, USP) As with other anesthetic agents, the individual response to Vetalar is somewhat varied depending upon the dose, general condition, and age of the subject so that dosage recommendations cannot e absolutely fixed.
Dosage -- Cats: a dose of 11 mg/kg (4 mg/lb) is recommended to produce restraint. Dosages form 22 to 33 mg/kg (10 to 15 mg/lb) produce anesthesia that is suitable for diagnostic or minor surgical procedures that do not require skeletal muscle relaxation. Subhuman primates: The recommended restraints dosages of Vetalar for the following species are. Cercocebus torquatus (white-collared mangabey). Papio cynocephalus (yellow Baboon). Pan Troglodytes versus (chimpanzee). Papio anubis (olive baboon). Pongo Pygmaeus (orangutan). Macaca nemestrina (pig-tailed macaque) 5 to 75 mg/kg: Presbytis entellus (entellus langur ) 3 to 5 mg/kg: Gorilla gorilla gorilla (gorilla) 7 to 10 mg/kg: Aotus trivirgatus (night monkey) 10 to 12 mg/kg: and Macaca tascicularis (crab-eating macaque). Macaca radiate (bonnet macaque). and Saimiri sciureus (squirrel monkey) 12 to 15 mg/kg. A single intramuscular injection produces restraint suitable for TB testing: radiography, physical examination, or blood collection.
HOW SUPPLIED Vetalar is supplied as the hydrochloride in concentrations equivalent to ketamine base.
N 0071-5584-10 Each 10 ml vial contains 100 mg/ml. Supplied in individual multi-dose vials (Steri Vials) and in cartons of 10.
CLINICAL STUDIES Vetalar has been clinically studied in subhuman primates in addition to those species listed under Dosage and Administration. Dosages for restraint in these additional species, based on limited clinical data, are Cercopithecus aethiops (grivet). Papio papio (guinea baboon) 10 to 12 mg/kg. Erythrocebus paths patas (patas monkey) 3 to 5 mg/kg: Hylobates lar (white-handed gibbon) 5 to 10 mg/kg: Lemur catta (ringtailed lemur) 7.5 to 10 mg/kg: Macaca fuscata (Japanese macaque) 5 mg/kg: Macaca speciosa (stumptailed macaque) and Miopithecus talapoin (mangrove monkey) 5 to 75 mg/kg: and Symphalangus syndactylus (siamangs) 5 to 7 mg/kg. ------------------ Taxonomy from "A Handbook of Living Primates" by Napier and Napier Academic Press. New York, NY.Back to Top
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