Aservo EquiHaler: Product Information

ASERVO EQUIHALER- ciclesonide spray, metered
Boehringer Ingelheim Animal Health USA Inc.

Caution:

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Description:

ASERVO EQUIHALER (ciclesonide inhalation spray) is a non-pressurized metered dose inhaler and drug cartridge combination containing a solution of 30 mg/mL of the prodrug ciclesonide, which is enzymatically converted to the pharmacologically active metabolite desisobutyrylciclesonide (des-ciclesonide) following inhalation. Des-ciclesonide is a glucocorticoid class of corticosteroid. Each actuation releases 343 mcg of ciclesonide. Inactive carrier ingredients include alcohol, purified water, and hydrochloric acid. The structural formula for ciclesonide is:

A picture of chemical structure

Indication:

ASERVO EQUIHALER is indicated for the management of clinical signs associated with severe equine asthma in horses.

Dosage and Administration:

For intranasal inhalation use only. ASERVO EQUIHALER may be used as part of the overall management of severe equine asthma in addition to other appropriate strategies to control clinical signs, such as environmental changes and bronchodilator therapy, as needed.

The initial dose of ASERVO EQUIHALER is 8 actuations (2744 mcg ciclesonide) twice daily for 5 days, followed by 12 actuations (4116 mcg ciclesonide) once daily for 5 days.

Total treatment duration is 10 days
Treatment days 1 to 5	8 actuations (puffs) Twice daily
Treatment days 6 to 10	12 actuations (puffs) Once daily

Prior to use, please refer to the detailed instructions for the handling and use of ASERVO EQUIHALER provided in this “User Manual”. ASERVO EQUIHALER should only be administered in the left nostril of the horse. Following careful and proper insertion, the ASERVO EQUIHALER should have a snug fit in the left nostril. A snug fit is required to ensure the horse receives a complete dose of ASERVO EQUIHALER.

Contraindications:

Do not use in horses with known hypersensitivity to ciclesonide or corticosteroids.

Warnings / Precautions:

Human Warnings: Not for use in humans. Keep this and all medications out of the reach of children. In case of accidental inhalation, seek medical advice immediately and show the package insert or the product label to the physician.

People with known hypersensitivity to ciclesonide or any of the excipients should avoid contact with ASERVO EQUIHALER.

Animal Safety Warnings and Precautions: Safe use of ASERVO EQUIHALER has not been evaluated in pregnant or lactating mares.

Clinical and experimental data have demonstrated that corticosteroids administered orally or by injection to animals may induce the first stage of parturition if used during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. Additionally, corticosteroids administered during pregnancy can be teratogenic. Therefore, ASERVO EQUIHALER should only be used in pregnant mares if the potential benefit justifies the potential risk to the fetus.

Administration of corticosteroids may worsen existing bacterial, fungal, or viral infection. Secondary infections should be ruled out before prescribing ASERVO EQUIHALER. Inhaled corticosteroids should be used with caution, if at all, in horses with active infection of the respiratory tract. If clinical signs do not improve or worsen despite administration of ASERVO EQUIHALER, the prescriber should consider additional diagnostic evaluation.

Due to the potential for exacerbation of clinical signs of laminitis, glucocorticoids should be used with caution in horses with a history of laminitis, or horses otherwise at a higher risk for laminitis.

Use with caution in horses with chronic nephritis, equine pituitary pars intermedia dysfunction (PPID), and congestive heart failure.

Concurrent use of other anti-inflammatory drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs) or other corticosteroids, should be approached with caution. Due to the potential for systemic exposure, concomitant use of NSAIDs and corticosteroids may increase the risk of gastrointestinal, renal, and other toxicity. Consider appropriate wash out times prior to administering NSAIDs or additional corticosteroids.

Other Warnings: Do not use in horses intended for human consumption.

Adverse Reactions:

The clinical safety of ASERVO EQUIHALER was assessed in a vehicle-controlled, randomized, double-blind 10-day field study followed by a 90-day open-label, extended-use field safety phase. In this field study, 319 client- or university-owned horses received either ASERVO EQUIHALER or vehicle control (the identical device containing the vehicle with no ciclesonide) during Phase 1.

Following Phase 1, 108 horses were enrolled in Phase 2, during which they could receive treatment for up to an additional 3 months. All horses in Phase 2 received the ASERVO EQUIHALER. Three hundred nineteen horses (163 ciclesonide and 156 control) of various breeds, 6 to 34 years of age, and weighing approximately 450 to 1,850 pounds were included in the field-study safety analysis. Adverse reactions that were reported in Phase 1 are listed in Table 1, and adverse reactions that were reported in Phase 2 are listed in Table 2.

The most common adverse reaction reported was coughing either during or immediately following inhalation of the test article (both ASERVO EQUIHALER and vehicle control groups).

Leukocytosis and/or neutrophilia developed in Phase 1 in several horses in both treatment groups, and in eight horses in Phase 2. Some of these horses also had concurrent clinical signs of infection, such as fever, which may have contributed to the leukocytosis. One ASERVO EQUIHALER-treated horse developed fever and leukocytosis characterized by a mature neutrophilia on Day 10 that was not present at screening. Other horses had possible alternate explanations for a stress leukogram, such as pain from a hoof abscess or poor acceptance of the device which may have caused stress from the study procedures.

In Phase 1, three ASERVO EQUIHALER-treated horses had increases in serum sorbitol dehydrogenase (SDH) above the reference range on Day 10 (high values were 12.4, 18.1 and 30.4 U/L); their baseline values were within the reference range (2-6 U/L). None of these horses had clinical signs attributable to elevated SDH levels. One horse also had an increase in serum gamma-glutamyltransferase (GGT) compared to baseline, but the GGT value at baseline was already above the reference range. By Day 40 of Phase 2, and again when measured at Day 100, this horse’s SDH and GGT values were within normal limits. In Phase 2, one horse developed an elevation in SDH (63.8 U/L) following the 6^th course of ASERVO EQUIHALER treatment. This horse had elevations in alkaline phosphatase (269 U/L, reference range 76-262 U/L), aspartate aminotransferase (511 U/L, reference range 194-431 U/L), and GGT (128 U/L, reference range 9-37 U/L). Reported adverse events in this horse at various time points during the study included coughing, nasal discharge, tachycardia, and hyperthermia. After the visit at which abnormal blood work was detected, the owner opted to withdraw the horse from the study (approximately Day 75).

In Phase 1, one horse developed severe hives 30 minutes after the fourth dose of ASERVO EQUIHALER. This horse was removed from the study due to this adverse reaction.

Table 1: Number (%) of Horses with Adverse Reactions in Phase 1 of field study

Adverse Reaction	ASERVO EQUIHALER (N=163) n (%)	Vehicle Control (N=156) n (%)
Cough	27 (16.6)	27 (17.3)
Nasal Discharge	17 (10.4)	17 (10.9)
Leukocytosis and/or neutrophilia	10 (6.1)	7 (4.5)
Sneezing	5 (3.1)	3 (1.9)
Nasal irritation/bleeding	2 (1.2)	3 (1.9)
Increase in serum Sorbitol Dehydrogenase (SDH)	3 (1.8)	0 (0)
Hives	1 (0.6)	0 (0)

* Horses may have had one or more reports of a given adverse reaction

Table 2: Number (%) of Horses with Adverse Reactions in Phase 2 of field study

Adverse Reaction	ASERVO EQUIHALER (N=100) n (%)
Cough	12 (12%)
Nasal Discharge	13 (13%)
Leukocytosis and/or neutrophilia	8 (8%)
Nasal irritation/bleeding	6 (6%)
Laminitis	3 (3%)
Sneezing	2 (2%)
Increase in serum Sorbitol Dehydrogenase (SDH)	1 (1%)

* Horses may have had one or more reports of a given adverse reaction

Laminitis was reported in three horses during Phase 2. Two of the horses were noted to have a history of or physical evidence of prior laminitic episodes. The third horse had no prior history of laminitis, was initially treated for thrush, and responded to conservative therapy within a few weeks. No definitive diagnosis of laminitis was made, and the examining veterinarian concluded the horse’s environment played a role in the development of clinical signs.

In Phase 1, in both treatment groups, nasal soreness, bleeding, scabs in the nostril, and redness of the nostril were reported in five horses.

In Phase 2, horses were reported to have epistaxis (2 horses), blood tinged discharge (1 horse), nose bloody and raw (1 horse), sensitive nostril (1 horse), and bright pink color of nasal mucus membranes (1 horse). One case of epistaxis was reported 9 days after the last dose administered, and one case was reported from the right nostril less than 24 hours following the last dose. The blood tinged discharge from the left nostril was reported 11 days following the last dose administered. In Tables 1 and 2, these similar clinical signs are summarized as nasal irritation/bleeding.

To report suspected adverse drug events and/or obtain a copy of the Safety Data Sheet (SDS) or for technical assistance, contact Boehringer Ingelheim Animal Health USA Inc. at 888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae