Metronidazole: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Metronidazole, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- AYRADIA™ (NADA/ANADA NADA 141-572)
AYRADIA™ NADA NADA 141-572, Original approval, October 11, 2023; sponsor Virbac AH, Inc.; species: Dogs; foi_id 14645; FDA PDF
Indication
Treatment of Giardia duodenalis infection in dogs.
Dose regimen
25 mg/kg (11.3 mg/lb), Oral (using the supplied syringe), Twice daily, Five consecutive days
25 mg/kg (11.3 mg/lb) of body weight, using the supplied syringe, twice daily for five consecutive days
Target-animal safety
dose multiples 0X, 1X, 2X, 3X, 5X; duration 15 consecutive days at 0X/1X/2X/3X (three times the intended duration); 5 consecutive days at 5X (intended duration), dosed every 12 hours; animals 40 (20 males and 20 females).
The objective of this study was to evaluate the safety of AYRADIA™ when administered orally to beagle puppies at one (1X), two (2X), or three (3X) times the intended dose for 15 consecutive days (three times the intended duration of treatment); or five (5X) times the intended dose for 5 consecutive days (the intended duration of treatment). Study Animals: The study enrolled 40 healthy beagle dogs (20 males and 20 females) approximately 12 weeks of age at the start of treatment and weighing between 3 to 4.7 kg.
| Finding | Quote |
|---|---|
| Increased number of dogs with, and observations of, ear erythema and diarrhea in the 5X group (Group 5) vs control and lower dose groups | There was an increased number of dogs with ear erythema and diarrhea, and an increased number of observations of ear erythema and diarrhea, in the highest dose group (Group 5) compared to the control and lower dose groups |
| Effects self-limiting; no veterinary intervention required | These effects were self-limiting and did not require veterinary intervention. |
| Table III.2 (number of dogs, Groups 1-5, n=8 each): well-defined ear erythema 0/0/1/1/2 dogs | Skin (ear) erythema, well- defined 0 0 1 1 2 |
| Table III.2 (number of dogs, Groups 1-5, n=8 each): moderate or marked soft or liquid stools 4/2/2/3/7 dogs | Soft or liquid stools, moderate or marked 4 2 2 3 7 |
| Study conclusion: supports 25 mg/kg twice daily for 5 days; 5X dosage associated with self-limiting diarrhea and ear erythema | Treatment with AYRADIA™ at five times the intended dosage was associated with self-limiting episodes of diarrhea and of erythema of the ears. |
| No inferential statistics because animals were not randomly assigned to groups | Because the animals were not randomly assigned to the treatment groups, inferential statistical analyses were not performed. |
| Tolerance study (investigational 160 mg/mL formulation): 10X daily dose (500 mg/kg/day) for 7 days caused severe neurologic signs by Days 7-8 | The 2 dogs that received the metronidazole oral suspension at 500 mg/kg/day exhibited severe neurologic signs by Days 7 and 8. Ataxia and lack of ocular reflexes were observed in both dogs. |
| Tolerance study: 5X daily dose (250 mg/kg/day) of an investigational suspension for 7 days; one of 2 dogs vomited bile on Day 4, no other adverse effects | One of the 2 dogs vomited bile the morning of Day 4. The dogs exhibited no other adverse clinical effects. |
Effectiveness
Randomized, masked, vehicle-controlled multi-site field study (10 sites in Germany, Portugal and Hungary; privately owned and shelter dogs) with 2:1 AYRADIA:vehicle allocation, 25 mg/kg orally twice daily for 5 consecutive days (Study No. U-409.010000-60006). Also a laboratory dose confirmation study (13 beagles, 7 treated / 6 control) with 99.7% trophozoite reduction.; n = 121 AYRADIA / 61 vehicle control; primary endpoint: Post-treatment Giardia cyst counts (IFA, Days 5-7): (1) LSMean of AYRADIA group significantly lower than vehicle control; (2) >= 90% reduction in post-treatment vs baseline cyst counts; result: Both primary endpoints met: post-treatment cyst count significantly less than vehicle control (p < 0.001; log difference -4.87); 99.91% reduction in cyst counts in the AYRADIA group (Table II.6).
AYRADIA™ 25 mg/kg BW (0.2 mL/kg BW), using the supplied syringe, twice daily for a period of five consecutive days (Day 0 to Day 4) 121 Vehicle control 0.2 mL/kg BW, using the supplied syringe, twice daily for a period of five consecutive days (Day 0 to Day 4) 61
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Diarrhea (vehicle-controlled field study) | 8 dogs (6.7%) | 3 dogs (5%) | The most common drug-related adverse reactions reported during the study were diarrhea (8 dogs [6.7%] in the AYRADIA™ group, 3 dogs [5%] in the control group) and vomiting (5 dogs [4.2%] in the AYRADIA™ group, 2 dogs [3.3%] in the control group). |
| Vomiting (vehicle-controlled field study) | 5 dogs (4.2%) | 2 dogs (3.3%) | The most common drug-related adverse reactions reported during the study were diarrhea (8 dogs [6.7%] in the AYRADIA™ group, 3 dogs [5%] in the control group) and vomiting (5 dogs [4.2%] in the AYRADIA™ group, 2 dogs [3.3%] in the control group). |
| Hyperactivity (vehicle-controlled field study) | one dog | Hyperactivity was reported in one dog in the AYRADIA™ group. | |
| Vomiting (active-controlled field safety study) | 13/91 (14.3%) | Of the 91 dogs treated with AYRADIA™, 13 (14.3%) exhibited vomiting, and 3 (3.3%) exhibited diarrhea. | |
| Diarrhea (active-controlled field safety study) | 3/91 (3.3%) | Of the 91 dogs treated with AYRADIA™, 13 (14.3%) exhibited vomiting, and 3 (3.3%) exhibited diarrhea. | |
| Adverse neurologic signs (active-controlled field safety study) | No adverse neurologic signs were reported during this study. |
Extraction notes: No pharmacokinetic data in the summary. Effectiveness quote is the Table II.5 group/regimen listing (grounds n per group); the result sentences read verbatim: 'For the first analysis, the post-treatment cyst count in the AYRADIA™ group was significantly less than in the vehicle control group (p < 0.001). The log difference between the groups was -4.87. For the second analysis, the percent reduction in cyst counts for the AYRADIA™ group was 99.9% (see Table II.6).' Table III.2 quotes reflect PDF extraction ('well- defined'). Active-controlled field safety study: 89 dogs received an active control veterinary product; control-group rates were not reported. Tolerance studies used a non-final 160 mg/mL formulation.
Reproduce: foi_structured_search(query="Metronidazole") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).