OSHA Hazard Information Bulletins
January 12, 1989
| MEMORANDUM FOR: |
REGIONAL ADMINISTRATORS |
| THROUGH: |
LEO CAREY
Director
Office of Field Programs |
| FROM: |
EDWARD BAIER
Director
Directorate of Technical Support |
| SUBJECT: |
Health Hazard Information Bulletin: Human Exposure and
Adverse Drugs Reaction from Vetalor (ketamine
hydrochloride) at Parke Davis of Morris Plains, New Jersey |
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.
Attachments
____________________________________________________________________________
Dept of Health and Human Services | ADVERSE DRUG REACTION, | Form
Public Health Service
| LACK OF EFFECTIVENESS,| approved
Food and Drug Admin.(HFV-210) | PRODUCT DEFECT REPORT | OMB
#0910-0012
5600 Fisher Lane
| (Forward to address at | use of this
| left)
| form is
| Attach all
| prohibited
| correspondence that | after April
| to this reaction.) | 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.)|2. DATE SENT TO FDA |3. TYPE OF
Olga Woo
| (Month, day, year) | REPORT
San Francisco Poison Control Center
| 6-10-88
| X INITIAL
San Francisco, CA (US)
|
|follow up
|
|to report
|
|of (give
|
| date)
_________________________________________|_____________________|____________
4. NAME, ADDRESS AND PHONE # OF ATTENDING
|5. NAME OR CASE
VETERINARIAN (In confidence)
| IDENTIFICATION OF
| OWNER (In confidence
Gary Rich, MD
|
Mills Hospital 100 S., San Mateo Drive
| 88-5584-001
San Mateo, CA 94401
|
(415) 696-4500
|
__________________________________________________|_________________________
SECTION I- DRUG DATA
TOPICAL
____________________________________________________________________________
6. TRADE, NAME AND GENERIC NAME(S) OF ACTIVE INGREDIENT(S)|7 a. Name of
(Include dosage form and strength. Ex. tab. 500 mg.)
| Manufacturer
Vetalar (ketamine hydrochloride injection)
| Parke Davis Co.
|_________________
|b. NADA NO.
| 045-290 (164)AP
__________________________________________________________|_________________
8. LOT NUMBER |9. DOSAGE REGIMEN AND ROUTE EX. 250 mg. |10. DATE(S) OF
| q 12 h.p.o.)
| ADMINISTRATION
|
| 02/03/88
_______________|__________________________________________|_________________
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
1 | 1 | C | human |
_____________________|_____________|________________|__________ |___________
15. CONCOMITANT MEDICAL PROBLEMS |c. AGE |d. WEIGHT
| |
____________________________________________________|___________|___________
|e. SEX
| __female __pregnant
| __male __neutered
____________________________________________________|_______________________
16. OVERALL STATE OF HEALTH AT TIME OF REACTION |17. DID ANY NEW ILLNESS
__GOOD __ FAIR __ POOR X CRITICAL | 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
_____________________|________|________________|____________________________
0 | | |
| | |
_____________________|________|________________|____________________________
FOR FDA USE ONLY
____________________________________________________________________________
1._____ __D __ NAI | COMMENT
2._____ __PR __ AI | G- HUMAN EXPOSURE, EYE(S) -9 0 SE
3._____ __PO __ AP | N- UNCONSCIOUS -9 10 Mr
4._____ __R __ AL | G- DEPRESSION/LETHARGY -9 2 HR
5._____ __NC |
6.____ | *VET ASSISTANT ACCIDENTALLY SQUIRTED IN EYE
T._____ | *PERSON TAKEN TO EMERGENCY ROOM
__ I.L. __ CL __ CONT |
____________________________|_______________________________________________
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 |22. DATE OF ONSET | 23. DURATION OF
ADMINISTRATION OF SUSPECT | (mo., day. yr.) | REACTION
DRUG AND ONSET OF REACTION | 02/03/88 | (Hrs.,days)
Few minutes | | 10 Minutes
__________________________________|___________________|_____________________
24. WAS THE ADVERSE REACTION |25. OUTCOME OF REACTION DATE
TREATED? | __ DIED (Give date)___________
| __ REMAINS UNDER TREATMENT
X NO __ YES(Describe | __ ALIVE WITH SEQUELAE
treatment | X RECOVERED
| __ UNKNOWN
__________________________________|_________________________________________
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
____________________________________________________________________________
Vetalar.
(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.
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