Carprofen: what the FDA reviewed for dog products

Rimadyl® Sterile Injectable Solution NADA 141-199, Supplemental approval, April 02, 2003; sponsor Zoetis Inc.; species: dog; foi_id 712; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis, and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs (supplement adds the postoperative pain claim).

Dose regimen

2 mg/lb (4.4 mg/kg) daily, as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, subcutaneous injection, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure

The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control o f postoperative pain, administer approximately 2 hours before the procedure.

Effectiveness

Three U.S. multicenter, placebo (0.9% saline)-controlled field studies of 2 mg/lb SC given ~2 h pre-surgery then once daily as needed: ovariohysterectomy (113 dogs, 13 sites; pivotal record here), cruciate repair (98 dogs, 10 sites) and aural surgery (120 dogs, 11 sites).; n = 113; primary endpoint: Veterinarian Visual Analog Scale (VAS) pain score, a priori contrasts of least squares means vs placebo at each time point; withdrawals for lack of effectiveness; result: Ovariohysterectomy study: Rimadyl-treated dogs significantly less painful at 4, 8 and 12 h post-surgery and on the first two Day 1 assessments (P<=0.05); 2 placebo and 0 Rimadyl dogs withdrawn for lack of effectiveness. Similar significant reductions in the cruciate (through Day 4) and aural (through first Day 1 assessment) studies.

One hundred and eleven of the 113 dogs enrolled in the study were included in the complete effectiveness analysis. Two dogs were excluded from part of the analysis (1 placebo-treated and one Rimadyl®-treated animal) because the Test Article was administered prior to the Day 0 baseline assessment. Duration of treatment is summarized in Table 1. Rimadyl ®-treated dogs required fewer additional treatments compared to dogs administered the placebo. Rimadyl®-treated dogs were significantly less painful 4, 8, and 12 hours post- surgery and on the first and second assessment on the first day after surgery (P £ 0.05).

Adverse reactions

Extraction notes: Supplemental NADA for the postoperative pain claim; no new target animal safety data ('No new animal safety data were required for approval of this supplement'). Effectiveness record uses the ovariohysterectomy field study (Study 1963C-60-99-360; 59 Rimadyl, 54 placebo); the cruciate study (48 Rimadyl/50 placebo) and aural study (61 Rimadyl/59 placebo) are summarised in design/result only. Adverse-reaction rows come from Table 3 (ovariohysterectomy study, n=113; columns Rimadyl % of dogs, Placebo % of dogs); Tables 6 and 9 (cruciate: e.g. Diarrhea 4.2 vs 2.0, Vomiting 4.2 vs 0; aural: Vomiting 1.6 vs 0, Inappetence 0 vs 1.7) not captured. Clinical-pathology observations (ALP, AST, WBC increases in a few dogs in both groups) described in text without incidence tables. Effectiveness quote preserves extraction artefacts ('post- surgery', 'P £ 0.05' for P<=0.05); dose quote preserves 'o f'.

Carprofen NADA 200-777, Original approval, April 10, 2024; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 15304; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily, Subcutaneous injection, once daily, or divided twice daily (1 mg/lb), for control of postoperative pain administer approximately 2 hours before procedure

The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily.

Extraction notes: Generic (ANADA) injectable solution (Felix Pharmaceuticals) approved on a biowaiver only: 'Based on the formulation characteristics of the generic product, Felix Pharmaceuticals Pvt. Ltd., was granted a biowaiver for the generic product Carprofen injectable solution.' RLNAD is RIMADYL injectable (NADA 141-199). The summary contains no PK, target animal safety, effectiveness or adverse reaction data (validator warning expected). The dosage quote is truncated at the first sentence because a page header interrupts the paragraph in the extracted text.

Carprofen Injection NADA 200-593, Original approval, April 19, 2017; sponsor Accord Healthcare, Inc.; species: Dogs; foi_id 222; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) once daily or 1 mg/lb (2.2 mg/kg) twice daily, subcutaneous injection, once daily or twice daily

2 mg/lb. (4.4 mg/kg) body weight once daily or 1 mg/lb. (2.2 mg/kg) body weight twice daily

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; bioequivalence waived on formulation characteristics (injectable solution with the same active ingredient, concentration and dosage form as RLNAD RIMADYL injection, NADA 141-199); 'CVM did not require effectiveness studies', 'CVM did not require target animal safety studies' and 'CVM did not require user safety studies'. No PK, safety, effectiveness or adverse-reaction data in the summary. Proprietary name given as 'Not Applicable'; established name Carprofen Injection.

Rimadyl® Caplets NADA 141-053, Supplemental approval, April 25, 2002; sponsor Zoetis Inc.; species: Dogs; foi_id 586; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis, and control of postoperative pain associated with soft tissue and orthopedic surgery in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, Oral (25, 75 and 100 mg scored caplets), once daily, or divided twice daily, For postoperative pain, administer approximately 2 hours before the procedure

The recommended dos age for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Effectiveness

Soft tissue surgery field studies 1963C-60-99-305 and -306: multicenter (15 sites), placebo-controlled field studies in client-owned dogs undergoing ovariohysterectomy or aural surgery; Rimadyl 2 mg/lb (4.4 mg/kg) orally approximately 2 hours before surgery then once daily as needed for 2 days (110 Rimadyl, 111 placebo); pain scored by veterinarians on a Visual Analog Scale (VAS) through Day 3; a priori contrasts among least squares means (repeated measures model).; n = 221 enrolled (two hundred and four in the complete effectiveness analysis); primary endpoint: Veterinarian VAS pain scores at each post-surgical time point (placebo vs Rimadyl least squares means); withdrawals for lack of effectiveness; result: Rimadyl-treated dogs were significantly less painful at 4, 8, 12, 24, 30 and 54 hours post-surgery (P<0.05); e.g. first postoperative VAS LSM 17.27 vs 21.34 mm (P=0.0098). One placebo and one Rimadyl dog withdrawn for lack of effectiveness. Conclusion: 2 mg/lb before surgery then once daily as needed for 2 days is safe and effective for postoperative pain from soft tissue surgery.

Results: Two hundred and four of the 221 dogs enrolled in the study were included in the complete effectiveness analysis. Seventeen dogs were excluded from part (n = 11) or the entire (n = 6) effectiveness analysis due to protocol deviations or failure to meet the enrollment criteria. Duration of treatment is summarized in Table 4. Dogs treated with Rimadyl® were significantly less painful 4, 8, 12, 24, 30, and 54 hours post-surgery (P < 0.05).

Adverse reactions

Extraction notes: Supplemental NADA adding the postoperative pain claim; no new target animal safety data required (safety referenced to the original FOI summary of October 25, 1996); no PK. Summary has no Species field; 'Dogs' taken from the indication. Dose quote reproduces the PDF artifact 'dos age' verbatim. Effectiveness and adverse reactions are from the larger soft tissue surgery studies; adverse reaction rows are Table 6 (abnormal health observations, number of dogs = 221) flattened by PDF extraction, column order Rimadyl % of dogs, placebo % of dogs. A separate cruciate repair study (1963C-60-99-304; 76 dogs, 38 Rimadyl / 38 placebo, 63 analyzed; 2 mg/lb before surgery then once daily as needed for 3 days) showed Rimadyl dogs significantly less painful at 4, 12, 24, ~28 hours and on Days 3-4 (P<=0.05), with 5 placebo vs 1 Rimadyl dog withdrawn for lack of effectiveness; its Table 3 lists diarrhea/soft stool 5.3% Rimadyl vs 0.0% placebo and vomiting 2.6% vs 0.0%.

Carprofen Caplets Novox® Caplets NADA 200-366, Original approval, April 27, 2005; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 1119; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), Caplets scored; dose in half-caplet increments

The total daily dose may be administered as 2 mg/lb (4.4 mg/kg) of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) of body weight twice daily.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such, not a clinical effectiveness study): randomized two-way crossover, single 25 mg oral dose, generic vs RIMADYL caplets, 36 fasted healthy beagles, 7-day washout.; n = 36; primary endpoint: Cmax and AUC0-LOQ 90% confidence interval within -20.00% to +25.00% of reference; result: Cmax and AUC0-LOQ within bioequivalence bounds; bioequivalence of generic and pioneer caplets achieved. In vitro dissolution supported a biowaiver for 75 mg and 100 mg caplets.

Protocol Title: A Randomized, Two-Way Crossover, Single-Dose, Open-Label Study to Evaluate the Relative Bioavailability of a Test Tablet Formulation of Carprofen (25 mg) Compared to an Equivalent Dose of a Commercially Available Reference Drug (RIMADYL Caplets, 25 mg, Pfizer, Inc.) in 36 Fasted, Healthy Dogs

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; effectiveness field holds the blood-level bioequivalence study. PK units taken from the text definitions (Cmax ng/mL, AUC0-LOQ ng-hr/mL, Tmax hr); the table itself prints no units. No adverse-event information given. Summary names the product 'Carprofen Caplets' (later NOVOX).

Carprieve® Chewable Tablets NADA 200-595, Original approval, April 28, 2017; sponsor Norbrook Laboratories, Ltd.; species: Dogs; foi_id 223; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure; scored tablets, half-tablet increments

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of bodyweight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such): randomized two-period, two-treatment crossover, 75 mg generic vs RIMADYL chewable tablet, 24 healthy intact male and female beagles, 33-day washout.; n = 24; primary endpoint: AUC and CMAX 90% confidence bounds within 0.80-1.25; result: Bioequivalence criterion met for AUC and CMAX; biowaiver granted for 25 mg and 100 mg tablets on dissolution (f2 76 and 62).

A randomized, two period, two treatment crossover study to evaluate the relative bioavailability of a generic 75 mg chewable tablet formulation of Carprieve® (carprofen) compared to an equivalent dose of the RLNAD RIMADYL® (carprofen) Chewable Tablets (Zoetis Inc., NADA 141-111) in 24 healthy male and female intact beagle dogs.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; 'CVM did not require effectiveness studies' and 'CVM did not require target animal safety studies'. Effectiveness field holds the bioequivalence study, which used the 75 mg strength. PK units quoted as printed (ppm).

Carprofen Tablets NADA 200-681, Original approval, August 04, 2020; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 9568; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure; scored tablets, half-tablet increments

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such; Study No. 017-01604): randomized, masked, two-period, two-sequence, single-dose crossover, 25 mg generic flavored tablet vs Rimadyl caplet, 24 fasted intact female beagles, 14-day washout.; n = 24; primary endpoint: CMAX and AUC 90% confidence interval of geometric mean ratios within 0.80-1.25 (mixed-effect model); result: Bioequivalence established for CMAX and AUC; biowaiver granted for 75 mg and 100 mg tablets because all strengths dissolved >85% in 15 minutes.

The in vivo blood-level study was conducted in 24 healthy, fasted beagle dogs.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; the FD&C Act 'doesn't require the sponsor to submit new effectiveness or target animal safety data'. Effectiveness field holds the bioequivalence study.

Rimadyl® Chewable Tablets NADA 141-111, Supplemental approval, August 21, 2002; sponsor Zoetis Inc.; species: Dogs/Canine; foi_id 642; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgery in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, Oral (25, 75 and 100 mg scored chewable tablets), once daily, or divided twice daily, For postoperative pain, administer approximately 2 hours before the procedure

The recommended dosag e for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Effectiveness

No new study. Postoperative pain claim bridged from the Rimadyl Caplets supplement (NADA 141-053, July 8, 2002) on the basis of comparable caplet/chewable bioavailability (NADA 141-111 FOI summary, May 14, 1999).; result: No new substantial evidence was required; chewable tablets at 2 mg/lb (4.4 mg/kg) once daily considered safe and effective for control of postoperative pain.

Based on the comparable bioavailability between caplet and chewable tablet (see NADA 141-111 FOI Summary, dated May 14, 1999), Rimadyl® Chewable Tablets administered at a dosage of 2 mg/lb (4.4 mg/kg) body weight once daily are safe and effective for the control of pain associated with soft tissue and orthopedic surgery in dogs.

Extraction notes: Supplemental NADA adding the postoperative pain claim to the chewable tablets; no new effectiveness, PK or target animal safety data (safety referenced to the original FOI summary of October 25, 1996). Effectiveness field records the bridging rationale only. Dose quote reproduces the PDF artifact 'dosag e' verbatim. Did not qualify for marketing exclusivity.

Carprofen Chewable Tablets NADA 200-575, Original approval, December 17, 2014; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 1251; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure; scored tablets, half-tablet increments

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such): randomized two-period, two-treatment crossover, 25 mg generic vs RIMADYL chewable tablet, 36 intact non-pregnant female beagles in two sets of 18, 7-day washout.; n = 36; primary endpoint: AUC and CMAX 90% confidence bounds within 80.00%-125.00%; result: Bioequivalence criterion met for AUC and CMAX; biowaiver granted for 75 mg and 100 mg tablets on dissolution (f2 73 and 62).

A randomized, two period, two treatment crossover study to evaluate the relative bioavailability of a test tablet formulation of carprofen (25 mg) compared to an equivalent dose of a commercially available reference drug product, RIMADYL (carprofen) Chewable Tablets (25 mg), sponsored by Zoetis Inc. under NADA 141-111, in 36 healthy, female, non-pregnant beagle dogs.

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; 'CVM did not require effectiveness studies' and 'CVM did not require target animal safety studies'. Effectiveness field holds the bioequivalence study. Approval date is garbled in the extracted text. No adverse-event information given.

Carofenvet™ NADA 200-762, Original approval, December 22, 2023; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs; foi_id 14867; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily; or 1 mg/lb (2.2 mg/kg) twice daily, Subcutaneous injection, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as either 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For control of postoperative pain, administer approximately 2 hours before the procedure.

Extraction notes: Generic (ANADA) injectable solution approved on a biowaiver only: 'Based on the formulation characteristics of the generic product, Cronus Pharma Specialities India Private Ltd., was granted a biowaiver for the generic product Carofenvet (carprofen) injectable solution.' RLNAD is RIMADYL injectable (NADA 141-199). The summary contains no PK, target animal safety, effectiveness or adverse reaction data (validator warning expected).

Carprofen NADA 200-739, Original approval, February 02, 2023; sponsor ZyVet Animal Health, Inc.; species: Dogs; foi_id 13434; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb daily; or 1 mg/lb twice daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover (OECD GLP) of generic vs RLNAD RIMADYL 25 mg chewable tablets in fasted male beagles, 7-day washout; n = 34; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

Study Animals: 34 intact male beagle dogs, between 8 months and 3 years of age and weighing between 6.81 and 12.00 kg.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). Product is a chewable tablet (25, 75, 100 mg). Biowaiver granted for 75 and 100 mg on dissolution similarity (f2 = 71.6 for 25 vs 75 mg; 78.9 for 25 vs 100 mg).

Carprofen Tablets NADA 200-732, Original approval, January 05, 2023; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 13317; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily; or 1 mg/lb (2.2 mg/kg) twice daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover (GLP) of generic vs RLNAD RIMADYL 25 mg caplets in fasted male beagles; n = 24; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

The laboratory study was conducted as a randomized, masked, two-period, two sequence, two-treatment, single-dose crossover design using 24 dogs with a 7-day washout between periods.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). Biowaiver granted for 75 and 100 mg tablets; all strengths dissolved >85% in 15 minutes so an f2 comparison was deemed unnecessary.

Carprofen Tablets NADA 200-767, Original approval, January 12, 2024; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 14968; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily; or 1 mg/lb (2.2 mg/kg) twice daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover (GLP) of generic 25 mg flavored tablet vs RLNAD RIMADYL 25 mg caplet in fasted male beagles, 7-day washout; n = 26; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

Study Animals: 26 purpose-bred, intact male, beagle dogs, ages 11 months to 3 years and weighing 9.8 kg to 12.1 kg.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). PDF extraction displaced the Table II.1 data rows to after the 'B. Bioequivalence Waiver' heading; the rows were quoted as extracted. Biowaiver granted for 75 and 100 mg tablets; all strengths dissolved > 85% in 15 minutes so an f2 comparison was deemed unnecessary.

Carprofen Tablets NADA 200-703, Original approval, July 07, 2021; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 11043; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily; or 1 mg/lb (2.2 mg/kg) twice daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover of the sponsor's flavored generic 25 mg tablet (ANADA 200-681) vs RLNAD Rimadyl 25 mg caplet in fasted female beagles; n = 24; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

The laboratory study was conducted as a randomized, masked, two-period, two-sequence, two-treatment, single-dose crossover design using 24 dogs with a 14-day washout between periods.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). This ANADA covers UNFLAVORED generic tablets; the in vivo study used the sponsor's approved flavored tablet (ANADA 200-681) and a biowaiver was granted for unflavored 25, 75 and 100 mg tablets because all dissolved >= 85% in less than 15 minutes (f2 test unnecessary).

Carprieve® Injection NADA 200-520, Original approval, July 12, 2014; sponsor Norbrook Laboratories, Ltd.; species: Dogs; foi_id 1213; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, subcutaneous injection, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure

The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as either 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For control of postoperative pain, administer approximately 2 hours before the procedure.

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; bioequivalence waived on formulation characteristics (same active ingredient, concentration and dosage form as RLNAD RIMADYL injectable, NADA 141-199); 'CVM did not require effectiveness studies' and 'CVM did not require target animal safety studies'. No PK, safety, effectiveness or adverse-reaction data in the summary.

Carprofen Caplets Novox® Caplets NADA 200-366, Supplemental approval, July 27, 2006; sponsor Dechra Veterinary Products LLC; species: Canine; foi_id 1120; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs (supplement adds the postoperative pain claim).

Dose regimen

2 mg/lb (4.4 mg/kg) once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, may be administered 2 hours prior to the procedure

For the relief of pain and inflammation associated with osteoarthritis, the total daily dose may be administered as 2 mg/lb (4.4 mg/kg) of body weight once daily or divided and administered as a 1 mg/lb (2.2 mg/kg) of body weight twice daily. For the control of postoperative pain, carprofen may be administered 2 hours prior to the procedure.

Effectiveness

No new study; supplement relies on the 25 mg blood-level bioequivalence study reported in the original ANADA FOI summary (April 27, 2005).; result: Postoperative pain claim added after pioneer exclusivity expired; safety and efficacy supported by prior bioequivalence.

The sponsor demonstrated in vivo bioequivalence via a blood-level bioequivalence study of the 25 m g generic and pioneer carprofen caplets to support the safety and efficacy of the generic product.

Extraction notes: Supplemental ANADA adding the postoperative pain claim; contains no new studies, PK, safety or adverse-reaction data. Species/Class recorded exactly as stated ('Canine'). Effectiveness quote preserves the extraction artefact '25 m g'.

Carprofen Chewable Tablets NADA 200-687, Original approval, July 29, 2020; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs; foi_id 9508; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily; or 1 mg/lb (2.2 mg/kg) twice daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover of generic vs RLNAD (Rimadyl) 25 mg chewable tablets in fasted male beagles; n = 36; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

The laboratory study was conducted as a randomized, masked two-period, two-sequence, two-treatment, single-dose crossover design using 36 male beagle dogs with a seven-day washout between periods.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). Suitability petition allowed added 37.5 mg and 50 mg strengths (37.5 mg unscored). Biowaiver granted for 37.5, 50, 75 and 100 mg strengths on dissolution similarity (f2 = 96.87, 96.87, 72.15, 78.36 vs generic 25 mg).

quellin® NADA 200-555, Original approval, June 13, 2013; sponsor Elanco US Inc.; species: Dogs; foi_id 1237; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb once daily or 1 mg/lb twice daily, oral, once daily or twice daily, For postoperative pain, administer approximately 2 hours before procedure

2 mg per pound (lb) of body weight once daily or 1 mg/lb twice daily for the control of postoperative pain; administer approximately 2 hours before procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such): randomized two-period, two-treatment crossover, 25 mg generic soft chewable tablet vs RIMADYL 25 mg tablet, 24 healthy non-pregnant female beagles, 14-day washout.; n = 24; primary endpoint: AUC and CMAX 90% confidence bounds within 0.80-1.25 (80.00%-125.00%); result: Bioequivalence criterion met for AUC and CMAX; biowaiver granted for 75 mg and 100 mg tablets on dissolution (f2 54-57).

A randomized, two period, two treatment crossover study to evaluate the relative bioavailability of a test tablet formulation of carprofen (25 mg) compared to an equivalent dose of a commercially available RLNAD RIMADYL (carprofen) tablets (25 mg) in 24 healthy female, non-pregnant beagle dogs.

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; 'CVM did not require effectiveness studies' and 'CVM did not require target animal safety studies'. Effectiveness field holds the bioequivalence study. Summary names the product 'LIBREVIA' (catalogue name quellin®). PK units are quoted exactly as printed ((μg/mL)*hour and μg/mL) although the magnitudes suggest ng-based units. No adverse-event information given.

CARPROFEN Chewable Tablets NADA 200-706, Original approval, June 28, 2021; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 11003; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb (4.4 mg/kg) daily; or 1 mg/lb (2.2 mg/kg) twice daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover (GLP) of generic vs RLNAD RIMADYL 25 mg chewable tablets in fasted dogs, 7-day washout; n = 28; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

Study Animals: 28 intact male dogs, aged 17 months to 31 months and weighing between 10 – 13 kg.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). Biowaiver granted for 75 and 100 mg chewable tablets on dissolution similarity (f2 = 58.7 for 25 vs 75 mg; 52.6 for 25 vs 100 mg).

Rimadyl® Sterile Injectable Solution NADA 141-199, Original approval, March 03, 2003; sponsor Zoetis Inc.; species: dog; foi_id 710; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs.

Dose regimen

1 mg/lb (2.2 mg/kg), subcutaneous injection, twice daily

The recommended dosage for subcutaneous administration to dogs is 1 mg/lb (2.2 mg/kg) of body weight twice daily.

Pharmacokinetics

Target-animal safety

dose multiples 1X (2 mg/lb = total daily dose), 2X (4 mg/lb); duration 3 days (single dorsoscapular SC injection; observations to 72 hours); animals 24.

The objective of the study was to evaluate injection sites in dogs after dorsoscapular subcutaneous administration of 2 mg/lb (4.4 mg/kg; total daily dose) and 4 mg/lb (8.8 mg/kg; 2x total daily dose) of Rimadyl® Injectable. (b) Test Animals: 24 purpose-bred Class A Beagle dogs

Effectiveness

No new clinical effectiveness study; effectiveness bridged from Rimadyl oral caplets (NADA 141-053) via two laboratory relative-bioavailability crossover PK studies (18 and 9 male Beagles, 25 mg dose).; primary endpoint: Total drug exposure (AUC) of SC injectable vs oral caplet after single dose and at steady state; result: Equivalent total drug exposure after first dose and at steady state; lower peak concentrations after SC; no additional clinical effectiveness studies required.

Based on the similar bioavailability of carprofen, when administered at the recommended dosage to dogs as either Rimadyl® oral caplets or Rimadyl® Injectable solution, no additional clinical effectiveness studies were required for approval of this NADA.

Adverse reactions

Extraction notes: Original NADA for the injectable; effectiveness rests on PK bridging to the oral caplet, not a field study. PK tables were flattened by PDF extraction: Table 1 rows list AUCss, Cmaxss, Cmaxss/Cmin, Cmaxss-Cmin, AUC0-12, Cmax (AUC in µg*hr/mL, Cmax in µg/mL); Table 2 AUC0-LOQ values (oral 102, IV 112, SC 105 µg*hr/mL; oral/IV 0.91, SC/IV 0.94) were not captured as separate entries. Target animal safety limited to injection-site toleration (saline control, T01-T04 groups); systemic safety referenced to NADA 141-053. Effectiveness n_dogs left null because the summary spells out 'Eighteen' and 'Nine' dogs.

Rimadyl® Sterile Injectable Solution NADA 141-199, Supplemental approval, March 25, 2003; sponsor Zoetis Inc.; species: dog; foi_id 711; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs (supplement adds a once-daily 2 mg/lb SC regimen).

Dose regimen

2 mg/lb (4.4 mg/kg) daily, as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, subcutaneous injection, once daily or twice daily (divided)

The recommended dose for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily.

Pharmacokinetics

Effectiveness

Laboratory two-period, two-sequence crossover PK study in 18 healthy male Beagles: 2 mg/lb carprofen SC at one site vs 1 mg/lb at two separate sites (Study 1560N-60-99-369); no clinical field study.; primary endpoint: Rate and extent of carprofen absorption (AUC, Cmax) one site vs two sites; bioequivalence limits; result: Results within bioequivalence limits; absorption rate and extent equivalent whether given once daily or twice daily.

Therefore, based upon the blood level comparison between one site and two site subcutaneous administrations, it is concluded that the rate constant (expressed as min-1) and extent (F) of carprofen absorption following subcutaneous injection will be equivalent whether carprofen is administered as a once daily or twice daily dose.

Adverse reactions

Extraction notes: Supplemental NADA adding the once-daily 2 mg/lb SC regimen. No new target animal safety data ('No new animal safety data were required for approval of this supplement'). Table 1 gives no units for AUC, Cmax, Tmax or half-life; values are quoted as printed with %CV. n_dogs left null because the summary spells out 'Eighteen'. Adverse-reaction quote preserves the extraction typo 'Ri madyl'.

Carprofen Flavored Tablets NADA 200-578, Original approval, March 25, 2015; sponsor Ajenat Pharmaceuticals LLC; species: Dogs; foi_id 1253; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure; scored tablets, half-tablet increments

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2. mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Effectiveness

No in vivo study; biowaiver (labelled as such) based on formulation (approved unflavored VETPROFEN caplets, ANADA 200-397, plus artificial beef flavor) and comparative in vitro dissolution of generic vs RLNAD 25, 75 and 100 mg tablets.; primary endpoint: In vitro dissolution profile comparison (USP apparatus II, pH 7.5 phosphate buffer, 50 rpm); result: All individual generic and RLNAD tablets >85% dissolved within 5 minutes at every strength; f2 comparison unnecessary; biowaiver granted for 25, 75 and 100 mg flavored tablets.

All the individual tablets for the generic drug product and RLNAD exhibited greater than 85% dissolution within 5 minutes for each of the tablet strengths. The profile comparison using a similarity factor is unnecessary under this circumstance.

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; bioequivalence waived on formulation characteristics plus in vitro dissolution; 'CVM did not require effectiveness studies' and 'CVM did not require target animal safety studies'. Effectiveness field records the dissolution biowaiver only. Dose quote preserves the printed '2.2. mg/kg'. No PK, safety or adverse-reaction data.

Rimadyl® Chewable Tablets NADA 141-111, Original approval, May 14, 1999; sponsor Zoetis Inc.; species: Dogs; foi_id 640; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs.

Dose regimen

1 mg/lb of body weight, Oral (25 mg, 75 mg and 100 mg scored chewable tablets; may be fed free choice or placed on food), twice daily, Dosage calculated in half-tablet increments

The recommended dosage for oral administration to dogs is 1 m g/lb of body weight twice daily.

Pharmacokinetics

Effectiveness

Bioequivalence (relative bioavailability) basis, not a clinical study: Study 2567A-60-97-106 (16 male Beagles; 25 mg strength crossover at 1.0 mg/lb and 75 mg strength parallel at 3.0 mg/lb) and follow-up Study 2567-60-98-090 (20 male Beagles; 75 mg strength two-period crossover at 3.0 mg/lb, 10-day washout), plasma carprofen by HPLC to 48 h; plus a 14-day palatability study (30 dogs) and in vitro dissolution supporting a waiver for the 100 mg tablet. Clinical effectiveness referenced to the original FOI summary for NADA 141-053.; n = 20; primary endpoint: 90% confidence intervals for AUC0-LOQ and Cmax of chewable tablet vs caplet within ±20% of the caplet mean; result: 25 mg strength: AUC and Cmax equivalent. 75 mg strength: not equivalent in the first study (Phase II) but equivalent in the follow-up crossover (AUC 381.2 vs 382.0; Cmax 44.5 vs 44.0; Tmax longer for chewable, 2.23 vs 1.48 h). 100 mg chewable tablet granted an in vivo bioequivalence waiver on dissolution similarity (f2 = 97). Palatability: 27 of 30 dogs consumed every tablet offered.

20 healthy male Beagle dogs approximately 8-9 m onths of age and ranging in weight from 20.8-31.1 lb were selected for the study.

Adverse reactions

Extraction notes: Original NADA for the chewable formulation; approval rests on bioequivalence to Rimadyl Caplets (NADA 141-053), so 'effectiveness' is labelled as the bioequivalence basis. No target animal safety studies were conducted with the chewable tablets (referenced to NADA 141-053). Summary has no Species field; 'Dogs' taken from the indication. Several quotes reproduce PDF extraction artifacts verbatim ('1 m g/lb', 'm onths'); the indication quote starts after the split word 'Rim adyl'. PK rows are table rows flattened by PDF extraction; see 'conditions' for column order. Adverse-reaction counts are spelled out in words in the source ('two', 'four'), so treated/control are left null; the vomitus quote reproduces the extraction break 'ma terial' verbatim. In the bioavailability studies, single episodes of vomiting and soft/loose stool were noted in two dogs per study and were self-limiting.

CARPRIEVE® NADA 200-498, Original approval, November 25, 2008; sponsor Norbrook Laboratories, Ltd.; species: Dogs; foi_id 1202; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure; scored caplets, half-caplet increments

2 mg/lb (4.4 mg/kg) of body weight. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such): single-dose, two-period, two-sequence crossover, 25 mg generic vs RIMADYL caplet, fourteen healthy adult dogs (7 males, 7 females), 35-day washout.; primary endpoint: AUC and CMAX 90% confidence interval within 80.00%-125.00%; result: AUC and CMAX within bounds; bioequivalence achieved; biowaiver granted for 75 mg and 100 mg caplets on dissolution (>90% dissolved by 15 min).

Fourteen dogs (7 males and 7 females) were blocked by weight without regard to sex and, within block, randomly assigned to either of two treatment sequences where the treatment sequences were reference followed by generic or vice versa. A 35-day washout interval separated the two periods.

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; effectiveness field holds the bioequivalence study; n_dogs left null because the summary spells out 'Fourteen'. Summary names the product 'NOROCARP Caplets' (catalogue name CARPRIEVE®). Page headers in the text read 'ANADA 200-489' (typo). No adverse-event information given.

Rimadyl® Chewable Tablets NADA 141-111, Supplemental approval, November 26, 2001; sponsor Zoetis Inc.; species: Dogs; foi_id 641; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs.

Dose regimen

2 mg/lb daily (as 2 mg/lb once daily or 1 mg/lb twice daily), oral (chewable tablet), once daily, or divided twice daily, supplement adds flexibility to give the total daily dose once daily

The recommended dosage for oral administration to dogs is 2 mg/lb daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb twice daily.

Extraction notes: Supplemental approval (Nov 26, 2001) allowing 2 mg/lb once daily instead of 1 mg/lb twice daily. No new studies: effectiveness relies on the original NADA 141-111 FOI (1 mg/lb BID) and the NADA 141-053 caplet supplement (2 mg/lb SID) plus the caplet/chewable comparable-bioavailability study; 'No additional clinical effectiveness data were required' and 'No new animal safety data were required'. No PK values are printed.

Carprofen NADA 200-490, Original approval, October 01, 2018; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 4860; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, oral, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure; scored tablets, half-tablet increments

The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of postoperative pain, administer approximately 2 hours before the procedure.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (labelled as such): randomized two-period, two-treatment, two-sequence crossover, 25 mg chewable tablet generic vs Rimadyl, 24 fasted female beagles, 14-day washout.; n = 24; primary endpoint: AUC and CMAX 90% confidence bounds within 0.80-1.25; result: Bioequivalence criterion met for AUC and CMAX; biowaiver granted for 75 mg and 100 mg tablets on dissolution (f2 54.5-70.4).

A randomized, two-period, two-treatment, two-sequence crossover study to evaluate the relative bioavailability of a generic 25 mg chewable tablet formulation of Carprofen compared to an equivalent dose of the RLNAD Rimadyl® (carprofen) chewable tablet (Zoetis Inc., NADA 141-111) in 24 healthy intact, non- pregnant, female beagle dogs.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; 'CVM did not require effectiveness studies' and 'CVM did not require target animal safety studies'. Effectiveness field holds the bioequivalence study. Table 1 lower bounds printed as '.94' and '.87'.

Carprofen Sterile Injectable Solution NADA 200-522, Original approval, October 15, 2014; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 1214; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs.

Dose regimen

2 mg/lb (4.4 mg/kg) daily, given as 2 mg/lb once daily or 1 mg/lb (2.2 mg/kg) twice daily, subcutaneous injection, once daily or twice daily (divided), For postoperative pain, administer approximately 2 hours before the procedure

The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered as either 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For control of postoperative pain, administer approximately 2 hours before the procedure.

Extraction notes: Generic (ANADA) approval: the summary states that new target animal safety and effectiveness data are not required; bioequivalence waived on formulation characteristics (injectable solution with the same active ingredient, concentration and dosage form as RLNAD RIMADYL injectable, NADA 141-199); no effectiveness or target animal safety studies required. No PK, safety, effectiveness or adverse-reaction data in the summary.

Rimadyl® Caplets NADA 141-053, Original approval, October 25, 1996; sponsor Zoetis Inc.; species: Dogs; foi_id 584; FDA PDF

Indication

Relief of pain and inflammation in dogs; clinically effective for relief of signs associated with osteoarthritis.

Dose regimen

1 mg/lb, oral, twice daily, Caplets are scored; dosage calculated in half-caplet increments. Field studies used 14-day courses.

The recommended dosage of Rimadylâ for oral administration in dogs is 1 mg/lb body weight twice daily. Caplets are scored and dosage should be calculated in half-caplet increments.

Target-animal safety

dose multiples 1X, 3X, 5X, 10X; duration Six weeks (42 days) for 1X, 3X, 5X; 10X group and second control treated for two weeks then sacrificed; animals 48 (4/sex/group in six groups).

48 male and female laboratory beagles, 8-13 months of age at study initiation, weighing from 7.1-11.9 kg. Dogs were randomly assigned to six treatment groups (4/sex/group).

Effectiveness

Multicentered (10 clinics), randomized, double-blind, placebo-controlled clinical field study (Report CR-G-5001-94); carprofen 1 mg/lb orally twice daily for 14 days vs placebo; evaluations Day 1, 4 and 15 with owner follow-up to Day 28.; n = 107 carprofen, 120 placebo; primary endpoint: Veterinary and owner assessment of overall positive response Day 1 to Day 15; graded lameness scores (lameness, weight bearing, joint mobility, willingness to raise contralateral limb, pain).; result: Positive improvement 81.3% carprofen vs 15.8% placebo by veterinarian and 81.3% vs 25.0% by owner (p < 0.001); mean cumulative lameness score improvement Day 1 minus Day 15 3.041 vs 0.137 (p = 0.0001).

Veterinary Evaluation Owner Evaluation Carprofen 81.3 (87/107) 81.3 (87/107) Placebo 15.8 (19/120) 25.0 (30/120) P-Value <0.001 <0. 001

Extraction notes: 1996 original NADA; the summary contains no pharmacokinetic section (only 'plasma concentrations of carprofen' listed as a measured parameter without values). No adverse-reaction table: the field studies state 'Adverse reactions to carprofen were not reported'; one carprofen dog had an ALT rise from 100 IU to 1166 IU and one dog given ibuprofen after carprofen had GI ulceration. The text renders the registered-trademark symbol as 'â' and the 'reflief' typo is in the source; quotes copy these verbatim. Target animal safety uses the pivotal six-week study (Study 05966); corroborative 13-week, 1-year and acute studies also present. A second (university, n=70) field study showed significant veterinary/owner improvement but non-significant lameness scores.

CARPROFEN Soft Chewable Tablets NADA 200-795, Original approval, September 05, 2024; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 15805; FDA PDF

Indication

relief of pain and inflammation associated with osteoarthritis and control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs

Dose regimen

2 mg/lb daily, Oral, once daily, or divided twice daily, for control of postoperative pain administer approximately 2 hours before the procedure

The recommended dosage for oral administration to dogs is 2 mg/lb of body weight daily.

Pharmacokinetics

Effectiveness

Blood-level bioequivalence study (not a clinical field study): randomized, masked, two-period, two-sequence, single-dose crossover (GLP) of generic 25 mg soft chewable tablet vs RLNAD RIMADYL 25 mg chewable tablet in fasted male beagles, 7-day washout; n = 28; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio generic:RLNAD within 0.80-1.25); TMAX summarized; result: Bioequivalence demonstrated; CMAX and AUC 90% CIs within acceptance limits

The in vivo blood-level study was conducted in 28 healthy, fasted beagle dogs.

Adverse reactions

Extraction notes: Generic (ANADA) approval: the summary states that effectiveness, target animal safety and human food safety data are not required. The effectiveness field holds the pivotal blood-level bioequivalence study (not a clinical field study); the PK rows are the Table II.1 bioequivalence parameters, whose columns are Generic mean, RLNAD mean, Ratio (generic:RLNAD), lower 90% CI, upper 90% CI (dagger = geometric mean, double dagger = arithmetic mean and SD). Suitability petition allowed a soft chewable dosage form (RLNAD is a compressed chewable). Dose quote truncated at first sentence because a page header interrupts the paragraph; the summary also allows 1 mg/lb twice daily and dosing about 2 hours before surgery. CMAX unit printed as ng/mL although values are in the same range as other summaries' μg/mL values; quoted as printed. Biowaiver for 75 and 100 mg granted on generic-vs-RLNAD dissolution similarity (f2 = 73.72, 70.45, 60.62 for 25, 75, 100 mg).

Rimadyl® Caplets NADA 141-053, Supplemental approval, September 27, 2001; sponsor Zoetis Inc.; species: Dogs; foi_id 585; FDA PDF

Indication

Relief of pain and inflammation associated with osteoarthritis in dogs.

Dose regimen

2 mg/lb daily (as 2 mg/lb once daily or 1 mg/lb twice daily), Oral (25, 75 and 100 mg scored caplets), once daily, or divided twice daily

The recommended dosage for oral administration to dogs is 2 mg/lb daily. The total daily dose may be administered as 2 mg/lb of body weight once daily or divided and administered as 1 mg/lb twice daily.

Effectiveness

Dose confirmation study 1960C-60-98-271: masked, placebo-controlled, multicenter (13 practices) clinical field study; carprofen 2 mg/lb orally once daily vs placebo caplet for 14 days in client-owned dogs with clinical and radiographic osteoarthritis (268 enrolled: 132 Rimadyl, 136 placebo; ages 8 months to 15 years); veterinarian and owner assessments (0-4 scale) on Day 0 and Day 13; 248 dogs suitable for the complete effectiveness analysis (24 excluded from part or all of the analysis).; n = 248 (complete effectiveness analysis); primary endpoint: Improvement of one grade or more (and two grades or more) in veterinarian composite and owner composite assessments of osteoarthritis severity, Day 0 to Day 13; result: Improvement >=1 grade: veterinarian composite 57.3% (71/124) carprofen vs 41.3% (52/126) placebo, P=0.008; owner composite 55.6% (69/124) vs 42.1% (53/126), P=0.029; lameness/weight-bearing 56.5% vs 37.3% (P=0.002); joint mobility 37.1% vs 15.9% (P<0.001); pain on palpation 59.7% vs 35.7% (P<0.001). Improvement >=2 grades: veterinarian composite 12.1% vs 4.0% (P=0.011); owner composite 15.4% vs 7.1% (P=0.041). Conclusion: 2 mg/lb once daily is safe and effective.

Dogs were randomly assigned to either carprofen or placebo treatment groups. The data from 248 animals were suitable for inclusion in the complete effectiveness analysis.

Adverse reactions

Extraction notes: Supplemental NADA adding the 2 mg/lb once-daily regimen; no new PK or target animal safety studies (safety referenced to the original FOI summary of October 25, 1996). Summary has no Species field; 'Dogs' taken from the indication. The extracted text carries a private-use glyph (U+F8E8, the registered-trademark symbol) immediately after 'Rimadyl' in several sentences, so quotes were anchored to avoid it (enrolment sentence '132 dogs were treated with Rimadyl and 136 dogs were treated with placebo' is therefore paraphrased in design rather than quoted). Adverse reaction rows are Table 3 as flattened by PDF extraction, column order: placebo number of dogs, placebo %, Rimadyl number of dogs, Rimadyl %; table header gives Placebo N=132 and Rimadyl N=129 (note this differs from the 132 Rimadyl / 136 placebo enrolled). Three carprofen dogs had >=3-fold ALT and/or AST increases (two >4-fold) without clinical signs. A European dosage characterization study (2167A-12-96-010, 43 dogs, 4 mg/kg once daily, 93% (40/43) improved after 5 days) is also described.