Milbemycin Oxime: what the FDA reviewed for dog products
7 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Milbemycin Oxime, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Cats; Dogs; Dogs and cats.
Products
- Interceptor™ (NADA/ANADA NADA 140-915)
- Interceptor™ (NADA/ANADA NADA 140-915 (supplement))
- MilbeGuard™ (NADA/ANADA 200-629)
Interceptor™ NADA NADA 140-915 (supplement), Supplemental approval, August 16, 1995; sponsor Elanco US Inc.; species: Dogs; foi_id 529; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis), control of adult Ancylostoma caninum (hookworm), and removal and control of adult Toxocara canis (roundworm) and Trichuris vulpis (whipworm) infections in dogs and in puppies four weeks of age or greater and two pounds of body weight or greater.
Dose regimen
0.5 mg/kg (0.23 mg/lb) minimum, Oral (tablet, swallow or chew), Monthly, Tablets sized by body weight (2.3 mg up to 10 lbs; 5.75 mg 11-25 lbs; 11.5 mg 26-50 lbs; 23.0 mg 51-100 lbs); supplement extends use to puppies four weeks of age or greater and two pounds or greater
The tablets supply the recommended minimum dose level of 0.5 mg milbemycin oxime per kilogram (0.23 mg/lb.) of body weight.
Target-animal safety
dose multiples 1X, 3X, 5X; duration Six weeks; one dose at 2, 4, 6 and 8 weeks of age (pivotal rising-dose study in beagle puppies beginning at 2 weeks of age); animals 12 per treated group (three groups) plus 12 placebo controls.
A six week safety study in beagle puppies beginning at 2 weeks of age, given oral doses of milbemycin oxime (as tablets) at dosage levels ranging from 5X to >30X the recommended minimum dose rate (0.5 mg/kg). Study Site: Liberty Research Post Office Box 107 Route 17C Waverly, NY 14892-0107 Study Director: Martin R. Gilman, Ph.D. Animals: Pure bred Beagle puppies. Three groups of 12 puppies each, 6 males + 6 females beginning at 2 weeks of age. Control - 1 group of 12 puppies received placebo tablets.
| Finding | Quote |
|---|---|
| Transient neurological signs at elevated doses: 10% of puppies reacted at 5-9 mg/kg, up to 83% at >15 mg/kg; all normal within 48 hours | Transient neurological signs were observed at elevated milbemycin oxime doses, in 10% of puppies that reacted at 5-9 mg/kg and up to 83% that reacted at doses greater than 15 mg/kg. |
| Reversible macrolide-induced syndrome at elevated doses, dose-dependent, not age or sex dependent | A typical, reversible macrolide-induced syndrome was observed at elevated doses of milbemycin oxime. |
| Diarrhea in two puppies each in the 1X and 3X groups | Two puppies in the 1X group and two in the 3X group exhibited diarrhea. |
| Neurological signs (trembling, vocalization, ataxia) in 13 puppies: placebo 1, 3X 4, 5X 8 | Thirteen puppies in the placebo (1), 3X (4) and 5X (8) groups exhibited neurological signs consisting of trembling, vocalization, and/or ataxia. |
| GGT slightly increased in 3X and 5X groups, not 1X | GGT (gamma glutamyl transferase) was slightly increased in the 3X and 5X groups but not the 1X group. |
| No adverse clinical signs or abnormal chemistry in 1X group; 3X signs only at 2 weeks of age; puppies four weeks and older had only minor neurological signs in 5X group | There were no animals in the 1X group observed with adverse clinical signs and abnormal clinical chemistry profiles. Animals (2 weeks of age) were observed in the 3X and 5X groups with adverse clinical signs. No clinical signs were seen in the 3X group at 4, 6 or 8 weeks. Puppies four weeks and older had only minor neurological signs in the 5X group. |
| Corroborative 2-week study (3 puppies/group, no control): unsteady gait, decreased activity and tremors in group 3 (11.5 mg) after second and third dosing; normal 24 hours post dosing | Unsteady gait and decreased activity in all animals in group 3 (11.5 mg) following the second and third dosing. |
Effectiveness
Corroborative analysis of puppies eight weeks of age or less extracted from the 1987-88 (heartworm/hookworm, 10 months) and 1989-90 (roundworm/whipworm, 60 days) well-controlled clinical field trials; monthly INTERCEPTOR at the recommended label dose (minimum 0.5 mg/kg).; n = 19 puppies (7 females and 12 males) in the roundworm/whipworm trial; twelve puppies in the earlier heartworm/hookworm trial; primary endpoint: Puppies cleared of nematode fecal egg shedding after a single treatment; heartworm-free at study end; result: Combined totals: heartworm prevention 7/7 (100%), hookworm removal 20/21 (95.2%), roundworm removal 18/19 (94.7%); control by study end: hookworm 17/18 (94.4%), roundworm 18/18 (100%).
A total of 19 puppies (7 females and 12 males) from four veterinary hospitals, three to eight weeks of age and enrolled in this field trial, received INTERCEPTOR (milbemycin oxime) at the recommended label dose.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Adverse reactions (1989-90 field trial puppies) | none noted | There were no adverse reactions noted during the study. | |
| Investigator-documented adverse reactions (1987-88 field trial puppies) | none | There were no investigator documented adverse reported reactions. Comments were received from owners, most concerning vomiting, diarrhea, and weight loss. However, these responses were not treatment related as determined by the investigator. |
Extraction notes: Supplemental approval (puppies four weeks of age or greater). Pivotal TAS study dose multiples are expressed as tablet counts (1X = one 2.3 mg tablet, 3X = three, 5X = five); by mg/kg the actual multiples ranged from about 6X (1X group at 2 weeks, 2.98 mg/kg) to about 29X (5X group at 2 weeks, 14.72 mg/kg), falling to 1.6X-9X at 8 weeks. Effectiveness n_dogs for the 1987-88 trial ('twelve puppies') is spelled out in the text; the two trials are not in one contiguous sentence. Combined efficacy totals are a flattened table ('Total = 7/7 = 20/21 = 18/19 X 100% = 100% = 95.2% = 94.7%').
MilbeGuard™ NADA 200-629, Original approval, December 19, 2018; sponsor Ceva Sante Animale; species: Dogs and cats; foi_id 6607; FDA PDF
Indication
Dogs: prevention of heartworm disease (D. immitis), control of adult hookworm (A. caninum), removal and control of adult roundworms (T. canis, T. leonina) and whipworm (T. vulpis) in dogs and puppies 4 weeks of age or greater and 2 lb or greater. (Cats: heartworm prevention and removal of adult A. tubaeforme and T. cati.)
Dose regimen
minimum 0.23 mg milbemycin oxime per pound (0.5 mg/kg) for dogs, oral, once a month, cats: minimum 0.9 mg/lb (2.0 mg/kg) once a month
Dogs: MilbeGuardTM Flavored Tablets are given orally, once a month, at the recommended minimum dosage rate of 0.23 mg milbemycin oxime per pound of body weight (0.5 mg/kg).
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 474.92 (μg/mL)*hour test vs 488.22 reference (geometric mean); ratio 0.97, bounds 92.85-101.91% | milbemycin oxime A3 analyte; dogs, single 5.75 mg tablet, two-period crossover, n=24; columns: test mean, reference mean, ratio, lower bound, upper bound | AUC (μg/mL)*hour 474.92† 488.22† 0.97 92.85 101.91 |
| cmax | 37.72 μg/mL test vs 38.45 reference (geometric mean); ratio 0.98, bounds 89.31-107.79% | milbemycin oxime A3 analyte; dogs, single 5.75 mg tablet, crossover, n=24 | CMAX (μg/mL) 37.72† 38.45† 0.98 89.31 107.79 |
| tmax | 1.43 hours test vs 1.46 reference (arithmetic mean) | milbemycin oxime A3 analyte; dogs, single 5.75 mg tablet, crossover, n=24 | TMAX (hours) 1.43‡ 1.46‡ NE NE NE |
| auc | 2632.33 (μg/mL)*hour test vs 2507.48 reference (geometric mean); ratio 1.05, bounds 100.10-110.10% | milbemycin oxime A4 analyte; dogs, single 5.75 mg tablet, crossover, n=24 | AUC (μg/mL)*hour 2632.33† 2507.48† 1.05 100.10 110.10 |
| cmax | 196.72 μg/mL test vs 187.33 reference (geometric mean); ratio 1.05, bounds 97.95-112.58% | milbemycin oxime A4 analyte; dogs, single 5.75 mg tablet, crossover, n=24 | CMAX (μg/mL) 196.72† 187.33† 1.05 97.95 112.58 |
| tmax | 1.61 hours test vs 1.58 reference (arithmetic mean) | milbemycin oxime A4 analyte; dogs, single 5.75 mg tablet, crossover, n=24 | TMAX (hours) 1.61‡ 1.58‡ NE NE NE |
Effectiveness
Bioequivalence study (not an effectiveness study): randomized two-period, two-treatment, single-dose crossover in dogs, 14-day washout, generic 5.75 mg MilbeGuard tablet vs RLNAD 5.75 mg Interceptor tablet; 90% CI of AUC and CMAX within 80-125%; n = 24; primary endpoint: AUC and CMAX of milbemycin oxime A3 and A4 analytes (bioequivalence limits 80-125%); result: Bioequivalence established between generic and RLNAD 5.75 mg tablets; no significant adverse reactions
Study Animals: 24 healthy beagle dogs, (13 female/11 male) weighing between 9.3-13.7 kg.
Extraction notes: Generic ANADA: 'CVM did not require effectiveness studies for this approval.' and 'CVM did not require target animal safety studies for this approval.' The effectiveness field holds the dog blood-level bioequivalence study (P12-022). PK values are from Tables II.1 and II.2 (dogs), columns: test mean, reference mean, ratio, lower bound %, upper bound %; AUC units are given as (μg/mL)*hour as extracted. A parallel cat bioequivalence study (26 cats, four-period double crossover; A3 AUC 378.12 vs 381.80 (ng/mL)*hour, CMAX 51.13 vs 50.86 ng/mL, TMAX 2 h) is not captured in the PK list. Biowaiver granted for 2.3, 11.5 and 23.0 mg strengths based on dissolution f2 = 63, 72, 72. Adverse reactions: 'No significant adverse reactions were reported in this study.'
Interceptor™ NADA NADA 140-915 (supplement), Supplemental approval, December 29, 1992; sponsor Elanco US Inc.; species: Dogs; foi_id 2007; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis), control of adult Ancylostoma caninum (hookworm), and removal and control of adult Toxocara canis (roundworm) and Trichuris vulpis (whipworm) infections in dogs over eight weeks of age. Supplement adds the roundworm and whipworm claims.
Dose regimen
0.5 mg/kg (0.23 mg/lb) minimum, Oral (tablet, swallow), Monthly, Tablets sized by body weight (2.3 mg up to 10 lbs; 5.75 mg 11-25 lbs; 11.5 mg 26-50 lbs; 23.0 mg 51-100 lbs); no change to formulation, dosage or regimen in this supplement
The tablets supply the recommended minimum dose level of 0.5 mg milbemycin oxime per kilogram (0.23 mg/lb.) of body weight.
Effectiveness
Multi-location well-controlled clinical field trial (Study No. MT-147-00-89; six clinics in Alabama, California, Florida and Texas, 1989-90): dogs with roundworm/whipworm infections randomized to monthly milbemycin oxime tablets (three treatments at 30-day intervals) or daily Filaribits Plus; fecal egg flotation at 7-10 days, 30 and 60 days. Supported by pivotal dose confirmation studies (roundworm 99.5%, whipworm 97.1%).; n = 231 enrolled (115 milbemycin oxime, 116 Filaribits Plus); 220 completed; primary endpoint: Cure (no eggs on fecal flotation) of roundworm and whipworm infections at 7 days and by study completion (60 days); result: Milbemycin oxime: 84 roundworm cases 98.8% cured at 7 days, 100% by day 60; 85 whipworm cases 96.5% at 7 days, 100% by day 60. Filaribits Plus: roundworm 76.7% at 7 days, 95.6% at 60 days; whipworm 62.9% at 7 days, 82.9% at 60 days.
A total of 231 patients were enrolled in the field trial, 115 in treatment group A (milbemycin oxime) and 116 in treatment group X (Filaribits Plus, Norden Laboratories). Of the 231 patients initially enrolled, 220 (95.28%) successfully completed the study regime.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Adverse side effects attributed to milbemycin oxime (field trial) | none | No adverse side effects were attributed to milbemycin oxime during the well controlled clinical field trial. |
Extraction notes: Supplemental approval adding roundworm (T. canis) and whipworm (T. vulpis) claims; no new TAS or PK data (referenced to original NADA 140-915). Field trial result sentences read verbatim: 'Treatment group A (milbemycin oxime) results were as follows: 84 cases of roundworm successfully cured, 98.8%, 7 days after the initial treatment, 100% by study completion (60 days); 85 cases of whipworm successfully cured 96.5%, 7 days after the initial treatment, 100% by study completion (60 days).' Table 4 totals (flattened): 'Totals Milbemycin oxime 111 84/84 =100% 85/85= 100%'.
Interceptor™ NADA NADA 140-915 (supplement), Supplemental approval, June 04, 1998; sponsor Elanco US Inc.; species: Dogs; foi_id 1996; FDA PDF
Indication
Prevention of heartworm disease in dogs and puppies four weeks of age or greater and two pounds body weight or greater.
Dose regimen
0.1 mg/kg (0.05 mg/lb) minimum, Oral (direct oral dosing), Once a month, Tablets: 2.3 mg (2-50 lbs), 5.75 mg (50.1-125 lbs); supplement changes dose from minimum 0.5 mg/kg to minimum 0.1 mg/kg with indication restricted to heartworm prevention
SAFEHEARTTM Tablets are given orally, once a month, at the recommended minimum dosage of 0.1 mg milbemycin oxime per kg of body weight (0.05 mg/lb).
Effectiveness
Well-controlled clinical field trial in client-owned dogs at three sites (Study No. CAH-4303-95-0096): monthly Safeheart tablets (minimum 0.1 mg/kg) vs positive control Interceptor Flavor Tabs (minimum 0.5 mg/kg) for 12 months; D. immitis microfilaria and antigen tests at months 5 and 12.; n = 134 of 150 enrolled completed; 66 low dose, 68 positive control; primary endpoint: D. immitis microfilaria and adult antigen status at months 5 and 12; result: All dogs in both groups negative for D. immitis microfilaria and adult antigen at months 5 and 12; 0.1 mg/kg provides effective heartworm prevention.
One hundred thirty-four (134) of the 150 client-owned dogs enrolled completed the 12 month study. Sixty-six (66) of the dogs that completed the study were in the low dose treatment group and sixty-eight (68) were in the positive control group.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Anorexia/appetite | 4 | 0 | Anorexia/appetite 4 0 |
| Vomiting | 3 | 3 | Vomiting 3 3 |
| Diarrhea | 3 | 1 | Diarrhea 3 1 |
| Lethargy | 2 | 1 | Lethargy 2 1 |
Extraction notes: Supplemental approval (Category II dose change). Summary product name is Safeheart™ although the catalogue lists Interceptor™. Dose establishment and target animal safety are referenced to the original NADA 140-915 FOI summary; no new TAS or PK data. Adverse reaction rows quoted from the clinical observations table; column order is Safeheart (n = 75) then Interceptor (n = 75) enrolled dogs. Result sentence reads verbatim: 'All dogs from both treatment groups were negative for D. immitis microfilaria and adult antigen at months 5 and 12.'
Interceptor™ NADA NADA 140-915, Original approval, June 14, 1990; sponsor Elanco US Inc.; species: Dogs; foi_id 528; FDA PDF
Indication
Prevention of heartworm disease caused by Dirofilaria immitis and control of adult hookworm infections caused by Ancylostoma caninum in dogs.
Dose regimen
0.5 mg/kg (0.23 mg/lb) minimum, Oral (tablet, swallow), Monthly, Tablets sized by body weight: 2.30 mg (up to 10 lbs), 5.75 mg (11-25 lbs), 11.50 mg (26-50 lbs), 23.0 mg (51-100 lbs)
The ingredients of INTERCEPTOR are formulated into various sized tablets to be administered orally (swallow) as appropriate for the weight of the dog (see below) at monthly dosing intervals. The tablets supply the recommended minimum dose level of 0.5 mg milbemycin oxime per kilogram (0.23 mg/lb.) of body weight.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| bioavailability | No significant difference (p>0.05) in bioavailability between the powder formulation and the commercial tablet | Bioequivalence corroborative study MB-147-0187; two-way crossover, eight dogs per group, 30-day washout; tablet of 5.68 mg providing a 0.5 mg/kg dose; serum milbemycin oxime by HPLC. No PK values reported. | Statistical analysis (ANOVA) of the pharmacokinetic parameters tested indicated no significant difference (p>0.05) in bioavailability between the two pharmaceutical dosage forms. |
| other | Milbemycin oxime in colostrum/milk 0.26 to 0.54 ppm | Milk samples from nursing bitches given exaggerated daily dosing (1.5 mg/kg/day, 3X monthly use rate) in the corroborative pregnant dog studies. | Analysis of milk samples from the nursing bitches described in the Pregnant Dog Studies determined the presence of milbemycin oxime at levels varying from 0.26 to 0.54 ppm. |
Target-animal safety
dose multiples 1X, 3X, 5X; duration Ten months; dosed daily for three consecutive days each month, starting in eight-week-old puppies (Study No. 382-122); animals 32 males and 32 females.
Animals were dosed monthly at 1X, 3X,and 5X the recommended use rate (0.5 mg/kg body weight). However, doses were given daily over three consecutive days each month for a total of ten months. animals: Purebred beagle dogs. Thirty-two males and 32 females. All animals were approximately eight weeks of age at initiation.
| Finding | Quote |
|---|---|
| 1X rate: all criteria similar to controls | All criteria observed at the 1x rate were similar to the control animals. |
| 3X rate: a few dogs had slight to mild transient trembling and/or ataxia during first three days only | At the 3X rate (dosed daily for three consecutive days) a few dogs exhibited slight to mild transient trembling and/or ataxia during the first three days of the study; no signs were observed during the remainder of the study. |
| 5X rate: transient trembling and/or ataxia in most dogs during first three days only | At the 5X rate (dosed daily for three consecutive days), transient trembling and/or ataxia was observed in most of the dogs during the first three days of the study; no signs were observed during the remainder of the study. |
| Initial signs attributed to over-dosage of young puppies (dose calculated for 11-25 lb adults; puppies averaged 4 lbs, i.e. 2.5-5X above targeted multiples) | Therefore, these dogs received a 2.5-5X increase in dosage over the targeted doses of 1X, 3X and 5X the recommended use rate. Side-effects were not seen at any subsequent dosing period. |
| Three deaths (one control, one 5X female day 3, one 1X male day 38) considered unrelated to treatment | One control male and one female dosed at the 5X use rate died on day 3 and one male receiving the 1X use rate died on day 38. These deaths were considered unrelated to administration of the test article because of the absence of clinical findings or any dose-response relationship. |
| No treatment-related effects on hematology, clinical chemistry, body weight, organ weight or pathology | No treatment-related effects were observed in any of the parameters for hematology, clinical chemistry, body weight, organ weight or pathology. |
| Acute study in 8-, 10- and 12-week-old puppies at 1X/5X/15X/25X for three days: ataxia and trembling dose-related, greatest at 25X, very slight at 5X, none at 1X | The incidence, severity, and length of occurrence were greatest at 25X, less at 15X, and very slight at 5X. Six of 12 animals at 5X showed no trembling or ataxia. |
| Heartworm-infected dogs with high microfilaremia: mild transient shock-like reaction | A mild, transient shock-like reaction was observed when milbemycin oxime was administered to certain heartworm-infected dogs with high microfilaremic counts. |
Effectiveness
Multi-location well-controlled clinical field trial (24 veterinary hospitals/clinics in nine states, 1987-88); heartworm-negative dogs randomized to monthly milbemycin oxime tablets (minimum 0.5 mg/kg) or the reference drug Filaribits Plus (Norden) for 10 months.; n = 769 milbemycin and 743 Filaribits Plus enrolled; 675 and 658 evaluated at month 10; primary endpoint: Heartworm prevention (D. immitis antigen and circulating microfilariae at 10 months) and hookworm control (fecal flotation), plus safety and owner acceptability; result: Heartworm prevention 100% in milbemycin group (only one milbemycin dog positive, documented as an occult infection admitted inadvertently); 97.5% of milbemycin dogs diagnosed with hookworm were fecal-negative by end of study (Table 3: 98%, 156/160).
Seven hundred and sixty-nine (769) milbemycin treated dogs and 743 Filaribits Plus treated dogs were enrolled in the clinical field trial. At the completion of the trial (month 10), 675 milbemycin oxime treated dogs and 658 Filaribits Plus treated dogs were evaluated for efficacy and safety.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Investigator-documented adverse effects (field trial) | none reported | none reported | There were no investigator-documented adverse effects reported in either treatment group during the course of the study. |
| Owner-reported vomiting, diarrhea, weight loss (field trial; not attributed to treatment) | Several comments were received from owners, most concerning vomiting, diarrhea, and weight loss. However, upon examination by the investigator none of these responses could be definitely attributed to either the test drug or reference treatment, but rather to changes in diet, housing situations, or some underlying medical problem. |
Extraction notes: Original NADA. No PK parameter values are reported; the bioequivalence corroborative study (MB-147-0187) reports only that no significant difference in bioavailability was found. TAS entry uses the pivotal 10-month chronic study (Study 2, No. 382-122); the acute puppy study (Study 3, No. 382-124: 60 puppies, 1X/5X/15X/25X for three days) and the reproduction study (3X daily; no reproductive effects) and heartworm-infected dog studies (1X/3X and 1X/5X) are summarized in findings/notes. Field trial result sentence reads verbatim: 'By the end of the study period, 97.5% of these dogs were negative on fecal examination.' Field trial adverse-event counts are not tabulated.
Interceptor™ NADA NADA 140-915 (supplement), Supplemental approval, March 10, 1998; sponsor Elanco US Inc.; species: Cats; foi_id 530; FDA PDF
Indication
Prevention of heartworm disease caused by Dirofilaria immitis and removal of adult Toxocara cati (roundworm) and Ancylostoma tubaeforme (hookworm) infections in cats six weeks of age or greater and 1.5 pounds body weight or greater.
Dose regimen
2.0 mg/kg (0.91 mg/lb) minimum, Oral (tablet), Once a month, Tablets by cat weight: 5.75 mg (1.5 to 6 lbs), 11.5 mg (6.1 to 12 lbs), 23.0 mg (12.1 to 25 lbs)
Interceptor Flavor Tabs for Cats are given orally, once a month, at the recommended minimum dosage of 2.0 mg milbemycin oxime per kilogram (0.91 mg/lb.) of body weight.
Target-animal safety
dose multiples 2.0 mg/kg, 6.0 mg/kg, 10.0 mg/kg; duration One treatment every 14 days for 90 days (90-day oral toxicity study in juvenile cats); animals 12 males, 12 females (four groups of 6).
Twenty-four Domestic Shorthair kittens (12 males, 12 females), two to three weeks of age and weighing between 147 and 273 grams at initiation, were divided into four groups of 6 cats each.
| Finding | Quote |
|---|---|
| All kittens survived; no clinical observations at one-hour post-dosing | All cats survived to termination. No clinical observations were seen at the one-hour post dosing observation period in either male or female animals. |
| No drug-related oculopathies; no body weight or food consumption differences vs controls | There were no drug- related oculopathies seen at either of the eye examinations. No significant differences in body weight or body weight gains occurred for any of the study animals when compared to controls. |
| No clinical pathology differences vs controls | No significant differences were observed in clinical pathology (hematology, clinical chemistry and urinalysis) values when groups receiving test article were compared to controls. |
| No treatment-related necropsy, organ weight or histopathologic findings | At necropsy, no observations were made which were considered to be related to the administration of the test article. There were no treatment-related changes in absolute organ weight data for either males or females when compared to controls. No identifiable histopathologic effects were observed. |
| Label restricted to kittens six weeks of age or greater and 1.5 pounds or greater based on weights/ages and doses administered | Based on the weights and ages of the kittens and the doses administered, it was determined that the label should restrict use to kittens six weeks of age or greater and 1.5 pounds body weight or greater. |
| Tolerability study, 8-week-old kittens at 20 mg/kg (10X): one test female died on day 12, relationship to treatment undetermined | One test group female died on study day twelve. On study day nine, this animal appeared to be losing weight, however, no overt signs of toxicity were noted. |
| Tolerability studies conclusion: safe at up to 10X the minimum recommended dose in 8-week-old kittens and young adults | Milbemycin oxime proved safe for eight week old kittens at dose levels up to 10X the minimum recommended dose. |
Effectiveness
Well-controlled multi-site clinical field trial in pet cats with natural Toxocara cati infections; single oral dose (minimum 1.0 mg/kg) vs placebo; fecal examination 7-10 days later. (Separate hookworm field trial: 65 milbemycin vs 32 placebo, 98.3% efficacy at minimum 2.0 mg/kg.); n = 76 cats milbemycin oxime, 38 cats placebo; primary endpoint: Negative fecal examination for roundworms 7-10 days post-treatment; result: 74/76 treated cats negative (97.1% efficacy) vs 4/38 placebo cats negative.
Of the 76 cats treated with milbemycin oxime, 74 were negative for roundworms at the 7-10 day evaluation for an efficacy of 97.1%. Of the 38 cases enrolled in the placebo group, 4 were negative for roundworms at the 7-10 day evaluation.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Death (roundworm field trial; cat under treatment for leg wounds; relationship undetermined) | one cat | One cat who was being treated for leg wounds died 1 day post treatment with milbemycin oxime. No necropsy was conducted. The relationship between the death and treatment with milbemycin oxime could not be determined. | |
| Adverse reactions (hookworm field trial) | none reported | Conclusions: Milbemycin oxime is safe and effective for use in cats at a minimum dose of 2.0 mg/kg for the removal of hookworms (Ancylostoma tubaeforme). Adverse Reactions: None reported |
Extraction notes: This NADA 140-915 supplement adds cats; all data are feline (species recorded as Cats; 'n_dogs' holds cat counts; 114 cats completed the roundworm field trial). No PK data. The death quote contains a soft hyphen (U+00AD) plus space in 'post-treatment' as rendered by the PDF extraction; 'drug- related' likewise reflects a hyphenated line break. TAS dose_multiples given as the tested mg/kg doses (2.0, 6.0, 10.0 mg/kg) because the summary states only that kittens 'were dosed at multiples of the minimum recommended dose (2.0 mg/kg)'; tolerability studies used 20 mg/kg described as 10X. A parallel 90-day study in young adult cats (3-4 months, same doses) showed no treatment-related effects.
Interceptor™ NADA NADA 140-915 (supplement), Supplemental approval, September 09, 1996; sponsor Elanco US Inc.; species: Dogs; foi_id 2001; FDA PDF
Indication
Prevention of heartworm disease (Dirofilaria immitis), control of adult Ancylostoma caninum (hookworm), and removal and control of adult Toxocara canis and Toxascaris leonina (roundworms) and Trichuris vulpis (whipworm) infections in dogs and puppies four weeks of age or greater and two pounds of body weight or greater. Supplement adds Toxascaris leonina.
Dose regimen
0.5 mg/kg (0.23 mg/lb) minimum, Oral (tablet, swallow or chew), Monthly, Tablets sized by body weight (2.3 mg up to 10 lbs; 5.75 mg 11-25 lbs; 11.5 mg 26-50 lbs; 23.0 mg 51-100 lbs)
The tablets supply the recommended minimum dose level of 0.5 mg milbemycin oxime per kilogram (0.23 mg/lb.) of body weight.
Effectiveness
Dose confirmation study (Trial AH-93-0045): 24 beagles (21.5 to 27 weeks old) experimentally infected with Toxascaris leonina eggs 75-77 days pre-treatment; 12 given a single 0.5 mg/kg minimum dose, 12 untreated; necropsy worm counts 7 days post-treatment. Supported by the 1989-90 field trial (100%, 62/62 roundworm cases cured).; n = 12 treated, 12 untreated controls; primary endpoint: Adult T. leonina worm counts at necropsy 7 days post-treatment; result: One adult worm recovered from 12 treated dogs vs 159 worms from 12 untreated controls; 99.4% efficacy.
One adult worm was recovered from the 12 treated dogs compared to 159 worms from the 12 untreated control dogs. The milbemycin oxime treatment was calculated to be 99.4% efficacious.
Extraction notes: Supplemental approval adding the Toxascaris leonina roundworm claim; no new dose establishment, TAS, PK or adverse reaction data (target animal safety referenced to original NADA 140-915). Design sentence reads verbatim: 'Twelve dogs were given a treatment of 0.5 mg/kg minimum dose of milbemycin oxime one time and 12 were untreated.'
Reproduce: foi_structured_search(query="Milbemycin Oxime") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).