Approval Date: November 9, 1987
Freedom of Information Summary
NADA 138-902
I. GENERAL INFORMATION:
NADA 138-902 Sponsor: Schering Animal Health
1011 Morris Ave.
Union, N.J. 07083Generic Name: tioxidazole Trade Name: Tiox Paste Marketing Status: Over the Counter (OTC) II. INDICATIONS FOR USE
Tiox (tioxidazole) Paste is indicated for removal of mature large strongyles (Strongylus edentatus, S.equinus , and S.vulgaris ), mature ascarids (Parascaris equorum and immature (4th larval stage) pinworms (Oxyuris equi ), and mature small strongyles (Triodontophorus spp ).
III. DOSAGE FORM(S), ROUTE OF ADMINISTRATION AND RECOMMENDED DOSAGE
IV. EFFECTIVENESS
The recommended dosage of tioxidazole is 5 mg per pound of body weight for one time treatment. The Tiox Paste syringe, calibrated in 250 pound weight increments, delivers 1.25 g of tioxidazole for each 250 pounds (see dosage table). One syringe will treat a 1250 pound horse one time at the recommended dose.
(Eds. note: The following table consists of 4 columns.)
Dosage Table Tiox Paste Syringe Horse Tiox paste oz g Tioxidazole Mark* Weight (lbs) Delivered Delivered 0 - - - 250 250 0.22 (6.25g) 1.25 500 500 0.44 (12/50g) 2.50 750 750 0.66 (18.75g) 3.75 1000 1000 0.88 (25.00g) 5.00 1250 1250 1.10 (31.25g) 6.25 * Use dial edge nearest syringe barrel to mark dose.Make sure the horse's mouth contains no feed. The paste is orally administered to horses by inserting the nozzle of the syringe through the interdental space (space between front and back teeth), and by depositing the required amount of paste on the base of the tongue by depressing the plunger. Immediately raise the horse's head for a few seconds after dosing.
A series of critical efficacy studies were carried out at the Schering Animal Health Research Center and at various other locations to demonstrate the efficacy of tioxidazole in horses.
Pivotal Studies
a. Trial: A-20182
Investigator:
Kwok L. Shun, Ph.D.
Kenneth Guito, B.S.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Therapeutic Equivalence
Design
Twelve naturally infected horses were divided into two groups of six animals each and were treated on day 0 with either Tiox Paste or Tiox Granules. Each product was given as a single oral dose of 11 mg/kg via stomach tube. The critical study method was used so that each animal served as its own control. Horses were purchased from local suppliers. Each animal was housed in an individual stall and acclimatized for a week before treatment.
On day -1, all animals were weighed. Parasite egg counts were performed on Day -1 and Day 0 using sugar flotation technique. Animals were divided into two treatment groups based on worm egg burden.
On Day 0, each animal received a calculated amount of Tiox granules paste. The animals were observed for one hour after treatment for spillage of drugs or any side effects due to the drug. Fecal material was collected daily from day -1 to day +7. All fecal samples were hand-picked under a microscope for small parasites. All parasites were fixed in 10% formalin and identified.
Animals were euthanized and necropsied 7 days after treatment, and fecal samples and residue worm burdens were examined. The details of necropsy worm recovery procedures and identification followed the description in "Guidelines for the Efficacy Evaluation of Equine Anthelmintics." Efficacy was determined using the critical test described in the guideline.
Results
The paste and granule forms of Tiox showed activity against the common adult and fourth stage equine parasites (Parascaris equorum, Strongylus vulgaris, S. edentatus, S. equinus, Oxyuris equi ) of 97.5%-100%. Activity against the mixed mature and immature small strongyles was 83.7% for the granules and 76-5% for the paste. Tiox was not active in either paste or granule form against Gastrophilus spp .
This study demonstrated the therapeutic equivalence of the paste and granule formulations. Accordingly, studies performed to demonstrate the efficacy of the NADA approved granules product (NADA 134-645, 12/26/85) may be referenced. These studies are discussed below.
This study was a laboratory study and was conducted in accordance with FDA's GLP regulations.
b. Trial: A-18345
Investigator: S. Kruckenberg, D.V.M., Ph.D.
Location: Manhattan, Kansas
Type of Study: Dose Confirmation
Design:
In this study Tiox (tioxidazole) Paste was administered as a single 11 mg/kg (5.0 mg/lb) oral dose to seven naturally parasitized adult horses. The drug was evaluated for drug side effects. Efficacy was determined against various species of worms. The critical study method was used to determine efficacy as described in (a) Trial A-20182.
Results:
Tiox (tioxidazole) Paste was 100% effective in reducing Parascaris equorum, Oxyuris equi (adult and immature), Strongylus vulgaris, Strongylus edentatus , and small strongyles in these horses. No effect was seen against Gastrophilus intestinalis or Gastrophilus hemorrhoidalis . No adverse drug reactions occurred.
The following studies were submitted in the Tiox Granules NADA 134-645.
c. Trial A-11200
Investigator: Eric Panitz, Ph.D.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Dose Titration
Design:
Twenty-one horses were treated with tioxidazole granules at 25 (n=l), 10 (8), 5 (8), or 2.5 (4) mg per kg body weight. The drug was administered as a top dressing on the grain. Total fecal materials were examined for parasites for 7-8 days after treatment. The animals were killed 7-8 days after treatment and the intestinal contents were examined for remaining parasites. Efficacy was determined using the critical study method as in (a) Trial A-20182.
Results:
Treating animals with 2.5 mg tioxidazole per kg was not effective against certain parasites, especially immature ascarids (0%) and large strongyles (range 20-68%). Animals treated with 5 mg per kg were cleared of nearly all parasites (94.6%) except for immature ascarids (50%). Treatment at 10 mg/kg was highly effective (96.6%) against the major classes of equine parasites (ascarids, large stongyles) found in the infected animals. The one animal treated with 25 mg per kg was cleared of all parasites studied.
d. Trial: A-I1201
Investigator: Eric Panitz, Ph.D.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Dose Titration
Design:
Five young horses and four ponies were given tioxidazole at 10 (n=5) or 22 (n=4) mg per kg body weight. These animals had been artificially infected with P. equorum ova recovered from feces from a naturally infected horse. The ova were embryonated in 0.05% formalin at room temperature for approximately 30 days. Embryonated eggs in a 0.1 ml volume were counted and used to estimate the volume required to yield 3000 embryonated ova. The animals were infected 43 (n=4) or 43 and 60 (n=l) days before treatment. Efficacy was determined using the critical study method described in (a) Trial A-20182.
Results:
Efficacy against ascarids in animals treated with 22 mg per kg was 100%. Efficacy in animals without evidence of prior ascarid infection treated at 10 mg per kg was 84.6%. Efficacy in animals with prior infections (natural or artificial) was 0% for 4th stage worms and 43.5% for immature worms.
Corroborative Studies
e. Trial: H-4-78
Investigator: Samuel M. Kruckenberg, D.V.M., Ph.D.
Location: Manhattan, Kansas
Type of Study: Dose Confirmation
Design:
In this study, tioxidazole was given on the feed to six horses at 11 mg/kg body weight (5 mg per pound). Efficacy was calculated using the critical study method as described in (a) Trial A-20182.
Results:
Ascarids and pinworms were removed 100% by treatment. Large strongyles were also eliminated by treated (S. vulgaris , 98.0%, S. equinus , 93.9%; S. edentatus , 95.9%).
f. Trial: 80-4-14
Investigators:
J. Drudge, D.V.M., Sc.D
E. Lyons, Ph.D.
and S. Tolliver, B.S.
Location: Lexington, Kentucky
Type of Study: Dose Confirmation
Design:
A series of 10 critical studies were conducted in naturally parasitized young (1-2 years) horses. Five horses were given tioxidazole at 11 mg/kg (5mg/pound) via stomach tube, while the remaining five were treated at the same level by mixing the drug in two liters of whole oats. Efficacy was calculated using the critical study method described in (a) Trial A-20182.
Results:
Efficacious removals (>90%) were recorded for large strongyles, ascarids, and both mature and immature pinworms. Feed administration tended to be more effective than tubing for S. edentatus (range 94-100% vs 71-99%). The reverse was true for S. vulgaris (range 42-100% for feeding vs 100% for tubing).
g. Trial: 80-4-203
Investigators:
E. Lyons, Ph.D.
J. Drudge, D.V.M., Sc.D.
and S. Tolllver, B.S.
Location: Lexington, Kentucky
Type of Study: Dose Confirmation
Design:
This experiment involved six horses (3 on feed, 3 with tube) given a newer formulation containing micronized tioxidazole granules at 11 mg/kg body weight (5 mg/pound). The other aspects of the experimental design were consistent with study (f) Trial 80-4-14.
Results:
Activity for S. vulgaris (100%), S. edentatus (91 to 100%), and immature O. equi (100%) was found. Complete removal of P. equorum was recorded for all horses infected except for one animal (93% removal).
h. Trial: V-77-001
Investigator: Marvin L. Sharp, D.V.M.
Location: Vernon, Texas
Type of Study: Dose Confirmation
Design:
Ten horses were treated by stomach tube with tioxidazole granules at 11 mg/kg body weight (5 mg per pound). Efficacy was determined using the critical study method as described in (a) Trial A-20182.
Results:
Efficacy was 95.2% against ascarids and 100% against pinworms. Large strongyles were treated effectively with tioxidazole (S. edentatus , 99.6%; S. vulgaris , 97.0%; no S. equinus were present).
i. Trial: H-10-77
Investigator: Samuel M. Kruckenberg, D.V.M., Ph.D.
Location: Manhattan, Kansas
Type of Study: Dose Confirmation
Design:
Ten horses were treated by stomach tube with tioxidazole granules at 11 mg/kg body weight (5 mg/pound). Efficacy was calculated using the critical study method as described in (a) Trial A-20182.
Results:
Efficacy was 97.8% vs S. edentatus and 100% against ascarids, pinworms, S. vulgaris, S. equinus , and small strongyles (Triodontophorus spp. )
j. Trial: H-3-78
Investigator: Samuel M. Kruckenberg, D.V.M., Ph.D.
Location: Manhattan, Kansas
Type of Study: Dose Confirmation
Design:
A total of six naturally parasitized horses were used in the study. They were given 11 mg tioxidazole per kg body weight (5 mg/ pound) via stomach tube. Efficacy was determined using the critical study method as described in (a) Trial A-20182.
Results:
No ascarids were present in these animals. Efficacy was 96.6% against S. edentatus and 100% against S. vulgaris, S. equinus , and O. equi (pinworms).
k. Trial: A-12466
Investigators: E. Panitz, Ph.D. and K. Shum, Ph.D.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Compatibility
Design:
Twenty horses were allotted to five groups of four animals each. Group A animals received no treatment. All animals in Groups B-E received tioxidazole at 11 mg/kg body weight (5 mg/pound) by stomach tube. Animals in groups B-E were also given a boticide, either carbon disulfide (CS2; 28 ml per horse), piperazine carbodithoic acid (Parvex, 88 mg/kg), trichlorfon (Combot, 40 mg/kg), or dichlorvus (Equigel,10 mg/kg), respectively. Fecal egg counts were taken at treatment and seven days after treatment. The animals were necropsied seven days after treatment and examined for residual worm burdens. Efficacy was evaluated by comparing aggregate residual instars and worm burdens of treated groups to controls for percent reduction. Egg count data were also evaluated for reductions of ascarid ova per gram and strongyle ova per gram.
Results:
Tioxidazole efficacy was greater than 99.9% when horses were also treated with carbon disulfide, piperazine carbodithoic acid, trichlorfon, or dichlorvos (critical study method). Ascarid egg counts were reduced 100%, and strongyle egg counts were reduced 97.6% or more.
The efficacy of tioxidazole has been demonstrated in previous work (a-j). This efficacy was not increased, decreased or adversely affected when tioxidazole was given in combination with each of the four boticides.
Carbon disulfide (89%), trichlorfon (93%), and dichlorvos (90% except 47% vs 3rd instar G. intestinalis ) were not adversely affected by tioxidazole in treatment of bots. Piperazine carbodithoic acid efficacy against G. intestinalis was lower (2nd stage 51.2%; 3rd stage 27.3%) than has been reported by other investigators.
In addition to the ten critical studies listed above, two non-critical efficacy studies were conducted, and the results are shown below:
l. Trial: A-13127
Investigators: E. Panitz, Ph.D. and K. Shum, Ph.D.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Dose Titration
Design:
Fourteen foals age 1-2 months were infected with approximately 5,000 embryonated ova of P. equorum . The animals were allotted to one of five groups: Group A was untreated control; Group B, 11 mg tioxidazole per kg 43 days after infection (A.I.); Group C, 22 mg per kg 43 days A.I.; Group D, 111 mg/kg 58 days A.I.; Group E, 22 mg/kg 58 days A.I. There were three animals in Groups A and C-D and two animals in Group B. Two to four weeks later, the animals were all treated with trichlorfon (Combot, 40 mg/kg) and thiabendazole (Thibenzole, 40 mg/kg). Total fecal materials were examined for worms for seven days following dual treatment (trichlorfon and thiabendazole). Geometric mean ascarid worm compared between each tioxidazole treatment group and the control group.
Results:
Worms recovered from each group were as follows: A, 143.0; B, 118.2; C, 244.9; D, 4.4; E, 18.6. Percent reduction was then 17.0%, 0%, 97.0%, and 86.9% for groups B-E, respectively.
m. Trial: V-80-003
Investigator: Doyne Hamm, D.V.M.
Location: Fayetteville, Arkansas
Type of Study: Treatment Interval
Design:
Sixty mares were divided into four groups of 15 and treated at the following times: 1) one month intervals for six months with tioxidazole; 2) two month intervals for six months with tioxidazole; 3) an initial three week interval then three month intervals for six months with tioxidazole; and 4) two month intervals for six months with mebendazole (Telmin) the positive control drug. Tioxidazole treatment was 11 mg/kg body weight (5 mg/pound). Mebendazole treatment was approximately 10 mg/pound body weight. Fecal samples were obtained prior to the first deworming, two weeks after the first deworming, and immediately prior to each subsequent deworming. Egg counts were conducted according to McMasters technique by Dr. Thomas Yazwinski, University of Arkansas.
Results:
Strongyle egg counts prior to treatment were above 2200 in all groups (total eggs per 15 grams - 1 gram per horse) with all horses showing some eggs. Ascarid egg counts varied widely (0-15 per horse). Following the first tioxidazole treatment, strongyle egg counts ranged from 7 (Group 1) to 61 (Group 3) for tioxidazole and were 218 for mebendazole, the positive control drug. Subsequent egg counts for group 1 ranged from 5 to 116; for group 2 from 423 to 986; for group 3 from 2701 to 2724, and for group 4 from 1376 to 1470.
n. Trial: A-18344
Investigator:
E. Lyons, Ph.D.
J. Drudge, D.V.M., Sc. D.,
and S. Tolliver, B.S.,
Mary Kay Schuette
Location: Lexington, Kentucky
Type of Study: Controlled study versus benzimidazole-resistant strongyles
Design:
Thirty mares were used in a non-critical field test to determine the equivalence of strongyle activity of granule and paste formulations of tioxidazole at 11 mg/kg. The mares were separated into 3 groups of 10 each. Group I received the paste formulation orally, Group II was fed the granule formulation on the grain ration, and Group III was non-treated.
Results:
The paste treated group had reductions of 87% for a strongyle eggs and 86% for small strongyle larvae. Large strongyle larvae were not present in cultures before or after treatment. The group treated with granules had 61% reduction in strongyle eggs. Small strongyle larvae were reduced 16% while large strongyle larvae were reduced 90-100%. In this study, the performance of the paste formulation of tioxidazole exceeded that of the granules.
The studies previously described, both critical and non-critical were laboratory studies. Controlled clinical studies were also conducted with tioxidazole. Summaries of these studies are presented below:
Clinical Trials
o. Trial: V82-001-07
Investigator: William J. Lee Jr., V.M.D.P.A.
Location: Pompano Beach, Florida
Type of Study: Clinical Field Trial
Number of Animals: 59
p. Trial: V82-001-02
Investigator: Dr. James H. Bailey
Location: Great Falls, Montana
Type of Study: Clinical Field Trial
Number of Animals: 59
q. Trial: V82-001-04
Investigator: DeWitt Owen Jr., D.V.M.
Location: Franklin, Tennessee
Number of Animals: 62
Design:
Trials o through q were all conducted using the same protocol. A total of 163 horses with pretreatment fecal egg counts, representative of common breeds, well distributed as to sex and age and managed in accordance with methods common to the United States, were used in these trials. Pretreatment and post-treatment fecal egg counts were evaluated as a measure of efficacy of Tiox Paste. Clinical observations were made to assess acceptability and safety of the drug under clinical use conditions.
Results:
Horses treated with Tiox Paste had either no fecal eggs observed or reduced fecal egg counts as compared to pretreatment values. There were no reports of advese effects, difficulty in administration or acceptability of the drug.
V. ANIMAL SAFETY
A series of studies were conducted to demonstrate the safety of treatment of horses with tioxidazole. Two studies were conducted to examine drug tolerance (Section III; studies s and v) and three were conducted for toxicity (Section IV; studies r, t, and u).
The two drug tolerance studies were conducted using multiples of the recommended dose, based upon the actual body weights of the test animals. In each of these two studies, horses received up to 40X (study s) or 25X (study v) the recommended dose without drug-related adverse effects.
The marketed product will be packaged to treat up to 1250 pounds (568 kg) of body weight in 250 pound increments, and under field conditions expected that the acutal dose given will correspond to the higher of the two possible doses where the body weight falls between any two of the 250 pound increments. Thus an 800 pound (364 kg) animal will be dosed as if it weighed 1000 pounds (454 kg) rather than 750 pounds (341 kg). For that reason, the three toxicity studies were conducted using a value of 1000 pounds (454 kg) for calculating doses to be administered.
In two of the toxicity studies, repeated (3 days) administration of 3X (study t) or 5X (Study u) the recommended dose produced no treatment-related changes in any of the parameters investigated. The third toxicity study using a single 5X (study r) dose also produced no treatment-related changes in any of the parameters measured.
All animals in study t weighed between 500 pound (227 kg) and 1100 pounds (500 kg), while all animals in study u weighed 726-968 pounds (330-440 kg). Most animals thus received somewhat more tioxidazole than if the doses had been calculated based upon actual body weight. The studies were therefore more rigid tests of the toxicity of tioxidazole than is evident from the summary of results.
All five studies were laboratory studies. Studies r, s, u, and v were conducted according the FDA's GLP regulations. Study t was conducted prior to the june 20, 1979, effective date for the GLP regulations. Although study t accordingly could not have been conducted in compliance with those regulations, study t was conducted in a scientifically sound appropriate manner.
r. Trial: A-15991
Investigator: Ruta M. Slepetys, B.S.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Oral Safety
Design:
Four adult horses (two mares and two geldings) were administered 5X the recommended dose of tioxidazole (12.5 g tioxidazole per 500 pounds body weight) as the paste formulation. Four control horses (two mares and two geldings) received an equivalent amount of vehicle alone. All treatments were administered once orally, directly into the mouth. A BSP liver function test was performed and blood, urine, and fecal samples were collected on days -1, 0 (immediately prior to treatment), +1, and +7. No animals died or displayed symptoms of overt toxicology during the study. Thus no gross necropsies or histopathological evaluations were performed.
Results:
There were no treatment-related effects seen on any of the parameters investigated. The margin of safety in this study is thus at least five times the recommended dose.
s. Trial: A-14864
Investigator: Ruta M. Slepetys, B.S.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Acute Toxicity
Design:
One mare and one gelding were given tioxidazole by stomach tube each day for three days. On day 1 the animals received 110 mg per kg body weight (10X recommended level), on day 2 each were given 220 mg/kg (20X), and on day 3 each received 440 mg/kg (40X). Animals were individually weighed prior to the start of the study, with doses calculated based upon that weight. Horses were observed each day following the three treatments and for two weeks after the last treatment for signs of clinical toxicity. Horses were then euthanized for gross necropsy and histopathology.
Results:
There were no changes in clinical parameters in either animal. Gross necropsy results and histopathological findings revealed no treatment-related effects. The margin of safety in this study is thus at least 40 times the recommended dose.
t. Trial: A-13485
Investigator: Ruta M. Slepetys, B.S. and Donald G. Campbell, Ph.D.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Oral Toxicity
Design:
Fourteen mares were allocated to four treatment groups. Animals were "taped" using a standard horse tape to confirm that they weighed between 500 and 1100 pounds (227-500 kg). Doses were calculated based upon a standard body weight of 1000 pounds (454 kg). Treatments were given mixed in the grain ration.
Group A horses (n=5) received approximately 33 mg tioxidazole per kg body weight (3X recommended dose) for 3 consecutive days. Group B consisted of two animals sampled at the same time as Group A and serving as untreated controls. Group C (n=5) animals received approximately 11 mg/kg body weight in a single oral treatment. Group D consisted of two animals sampled at the same time as Group C and serving as untreated controls. Serum, plasma, urine, and fecal samples were collected for analysis, and a BSP liver function test was performed. Groups A & B were sampled on days -1, 0 (immediately prior to treatment), +1, +3, and +9. Groups C & D were sampled on days -1, 0, +1, and +7.
Results:
Neither dose level of tioxidazole produced any appreciable, consistent changes in the physiological parameters measured. The margin of safety in this study is thus at least three times the recommended dose, even when given every day for three consecutive days.
u. Trial: A-14565
Investigator: Ruta M. Slepetys, B.S.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Oral Toxicity
Design:
Six horses (3 mares, 3 geldings) were administered approximately 55 mg tioxidazole per kg body weight (5X recommended dose) via stomach tube once a day for three days. Animals were individually weighed prior to treatment (range 726-968 pounds or 330-440 kg). Doses were calculated based upon a standard body weight of 1000 pounds (454 kg). One mare and one gelding served as sham-treated controls. A BSP liver function test was performed and serum, plasma, urine, and fecal samples were collected on days -1, 0 (immediately prior to treatment), +1, +3, and +9. All horses were euthanized after the last sample for gross necropsy and histological evaluation.
Results:
There were no treatment-related effects seen on any of the parameters investigated. The margin of safety in this study is thus at least 5 times the recommended dose when given for 3 times the recommended treatment period.
v. Trial: A-18352
Investigator: Ruta M. Slepetys, B.S.
Location:
Schering Animal Health Research Center
Allentown, N.J.
Type of Study: Oral Toxicity
Design:
Six horses (3 mares, 3 geldings) were weighed and doses calculated based upon actual body weights. Animals were administered approximately 275 mg tioxidazole per kg body weight (25X recommended dose) once orally via mixing in the feed. All medicated feed was consumed as readily as unmedicated feed. Three mares and two geldings served as controls. A BSP liver function test was performed and serum, plasma, urine, and fatal samples were collected on days -1, 0 (immediately prior to treatment), +1, +2, +3, +7, +9, and +14. No animals died or displayed symptoms of overt toxicity. Thus, no gross necropsies or subsequent histopathological evaluations were performed.
Results:
Changes in the parameters investigated were limited to isolated occurrences in treated animals that were not readily attributable to treatment, i.e. weight loss in one animal and increased SGOT in another. Other changes, i.e. elevated band cell number, increased BSP clearance times and fecal occult blood occurred with equal frequency in controls and were also noted prior to treatment. There were no other biologically significant changes, but no necropsies or histopathology was done.
VI. HUMAN SAFETY:
Data on human safety pertaining to human consumption of drug residues in food were not required for approval of this NADA. The drug is approved for use only in horses that are not to be used for food and is to be labeled: NOT FOR USE IN HORSES INTENDED FOR FOOD. With respect to human safety relating to possession, handling, and administration, no special caution statement is needed.
VII. AGENCY CONCLUSIONS:
The data submitted in support of this NADA satisfy the requirements of Section 512 of the Act and Section 514.111 of the implementing regulations. Those data demonstrate that Tiox (tioxidazole) Paste, when used under its labeled conditions of use, is safe and effective.
Tiox (tioxidazole) Paste is approved for OTC use because the product has been shown to be effective against all important parasites detrimental to the health of the horse (Strongylus edentatus, S. equinus, S. vulgaris, Parascaris equorum, Oxyuris equi and Triodontophorus spp. ). Directions for oral administration of Tiox (tioxidazole) Paste can reasonably be followed by the laymen.
VIII. LABELING (Attached)
1. Tiox(TM) (tioxidazole) Paste product label
2. Tiox(TM) (tioxidazole) Paste shelf carton label
3. Tiox(TM) (tioxidazole) Paste package insert
Copies of these labels may be obtained by writing to the:
Food and Drug Administration
Freedom of Information Staff (HFI-35)
5600 Fishers Lane
Rockville, MD 20857
Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.