Cyclosporine

Cyclosporine Capsules, USP MODIFIED are indicated for the control of atopic dermatitis in dogs weighing at least 4 lbs. (1.8 kg) body weight.

Sporimune™

For the management of chronic keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK) in dogs.

Place ointment directly on cornea or into the conjunctival sac. For ophthalmic use in dogs only. Safety of use in puppies, pregnant or breeding animals has not been determined. US Federal law restricts thiis drug to use by or on the order of a licensed veterinarian.

Optimmune®

For the control of atopic dermatitis in dogs weighing at least 4 lbs. (1.8 kg) body weight.

Federal law restricts this drug to use by or on the order of a licensed veterinarian.ATOPICA is contraindicated for use in dogs with a history of neoplasia.For use in dogs only.Capsules should not be broken or opened.

Atopica™

Indication: MODULIS® for Cats is indicated for the control of feline allergic dermatitis as manifested by excoriations (including facial and neck), miliary dermatitis, eosinophilic plaques, and self-induced alopecia in cats at least 6 months of age and at least 3 lbs (1.4 kg) in body weight.

Modulis® for Cats (cydosporine oral solution) USP Modified

INDICATIONS: OPTIMMUNE Ophthalmic Ointment is indicated for management of chronic keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK) in dogs.

Optimmune® (0.2% Cyclosporine, USP) Ophthalmic Ointment

Indications: MODULIS® for Dogs is indicated for the control of atopic dermatitis in dogs weighing at least 4 lbs. (1.8 kg) body weight.

Modulis® for Dogs (cyclosporine oral solution) USP MODIFIED 100 mg/mL

Sporimune is indicated for the control of atopic dermatitis in dogs weighing at least 4 lbs. (1.8 kg) body weight.

Sporimune™ (cyclosporine capsules) USP MODIFIED

Clinical Pharmacology: Cyclosporine is an immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2. It does not depress hematopoiesis or the function of phagocytic cells. Cyclosporine is not a corticosteroid or antihistamine. Following an intravenous dose of 2 mg/kg in a 24-hour fasted state, clearance of cyclosporine A in cats was 0.199 L/kg × h and half life was ~24 hours. After oral administration, the terminal elimination half life has been estimated to be as short as 6.8 to longer than 40 hours in some normal healthy cats. The bioavailability of cyclosporine is highly variable both within and between cats. A pharmacokinetic study showed no consistent difference in the mean extent of drug absorption when administered orally to fed or fasted cats or mixed in with food. Blood levels of cyclosporine in field studies were highly variable, even among cats with similar clinical response, suggesting no generalizable correlations can be made between cats with regard to blood cyclosporine levels and clinical response (effectiveness and safety). Nevertheless, individual differences in the relationship between drug exposure and clinical response may exist. Therefore, to minimize individual fluctuations in drug absorption, MODULIS® for Cats should be administered on a consistent schedule with regard to meals and time of day.

Modulis® for Cats (cydosporine oral solution) USP Modified

Cyclosporine is an immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2. It does not depress hematopoesis or the function of phagocytic cells. ATOPICA for Cats is not a corticosteroid or antihistamine. Following an intravenous dose of 2 mg/kg in a 24-hour fasted state, clearance of cyclosporine A in cats was 0.199 L/kg x h and half life was ~24 hours. After oral administration, the terminal elimination half life has been estimated to be as short as 6.8 to longer than 40 hours in some normal healthy cats. The bioavailability of ATOPICA for Cats is highly variable both within and between cats. A pharmacokinetic study showed no consistent difference in the mean extent of drug absorption when administered orally to fed or fasted cats or mixed in with food. Blood levels of cyclosporine in field studies were highly variable, even among cats with similar clinical response, suggesting no generalizable correlations can be made between cats with regard to blood cyclosporine levels and clinical response (effectiveness and safety). Nevertheless, individual differences in the relationship between drug exposure and clinical response may exist. Therefore, to minimize individual fluctuations in drug absorption, ATOPICA for Cats should be administered on a consistent schedule with regard to meals and time of day.

Atopica™ for Cats (cyclosporine oral solution) USP MODIFIED 100 mg/mL

Cyclosporine is a immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2. It does not depress hematopoiesis or the function of phagocytic cells. A decrease in CD4 and CD8 cells was not seen in dogs receiving 20 mg/kg/day of cyclosporine for 56 days. Cyclosporine is not a corticosteroid or an antihistamine. METABOLISM: Cyclosporine is extensively metabolized by the cytochrome P-450 enzyme system in the liver, and to a lesser degree in the gastrointestinal tract and the kidney. The metabolism of cyclosporine can be altered by the co-administration of a variety of agents (See Precautions).

CYCLAVANCE® (cyclosporine oral solution) USP MODIFIED

Cyclosporine is an immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2. It does not depress hematopoesis or the function of phagocytic cells. A decrease in CD4 and CD8 cells was not seen in dogs receiving 20 mg/kg/day of cyclosporine for 56 days. Sporimune (cyclosporine capsules) USP MODIFIED is not a corticosteroid or an antihistamine.

Sporimune™ (cyclosporine capsules) USP MODIFIED

Clinical Pharmacology: Cyclosporine is an immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2. It does not depress hematopoiesis or the function of phagocytic cells. A decrease in CD4 and CD8 cells was not seen in dogs receiving 20 mg/kg/day of cyclosporine for 56 days. MODULIS® for Dogs is not a corticosteroid or an antihistamine.

Modulis® for Dogs (cyclosporine oral solution) USP MODIFIED 100 mg/mL

Cyclosporine is an immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2. It does not depress hematopoesis or the function of phagocytic cells. A decrease in CD4 and CD8 cells was not seen in dogs receiving 20 mg/kg/day of cyclosporine for 56 days. ATOPICA is not a corticosteroid or an antihistamine.

Atopica™

Contraindications: Do not use in cats with a history of malignant disorders or suspected malignancy. Do not use in cats infected with feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV). Do not use in cats with a hypersensitivity to cyclosporine.

Modulis® for Cats (cydosporine oral solution) USP Modified

Contraindications: MODULIS® for Dogs is contraindicated for use in dogs with a history of neoplasia. Do not use in dogs with a hypersensitivity to cyclosporine.

Modulis® for Dogs (cyclosporine oral solution) USP MODIFIED 100 mg/mL

CYCLAVANCE is contraindicated for use in dogs with a history of neoplasia. Do not use in dogs with a hypersensitivity to cyclosporine.

CYCLAVANCE® (cyclosporine oral solution) USP MODIFIED

CYCLAVANCE (cyclosporine oral solution) is a systemic immunosuppressant that may increase the susceptibility to infection and the development of neoplasia. HUMAN WARNINGS: Not for human use. Keep this and all drugs out of reach of children. For use only in dogs. Special precautions to be taken when administering CYCLAVANCE in dogs: Do not eat, drink, smoke, or use smokeless tobacco while handling CYCLAVANCE. Wear gloves during administration. Wash hands after administration. In case of accidental ingestion, seek medical advice immediately and provide the package insert or the label to the physician. People with known hypersensitivity to cyclosporine should avoid contact with CYCLAVANCE. People with known hypersensitivity to cyclosporine should avoid contact with CYCLAVANCE.

CYCLAVANCE® (cyclosporine oral solution) USP MODIFIED

SAFETY: A target animal safety study and clinical field studies with OPTIMMUNE Ophthalmic Ointment showed a wide safety margin in adult dogs. In the 6-month target animal safety study, dogs were subjected twice daily to up to 10 times the approved concentration of OPTIMMUNE Ophthalmic Ointment. No apparent toxicity or adverse reactions were observed. Dogs in this study were vaccinated with commercially available vaccines. No effect on antibody titer response was noted. Epiphora was noted in all groups, including the placebo group, and was not associated with any inflammatory change, nor was there any correlation to gross and histopathological changes.

Optimmune® (0.2% Cyclosporine, USP) Ophthalmic Ointment

Warnings: MODULIS® for Cats is a systemic immunosuppressant that may increase the susceptibility to infection and the development of neoplasia. One of 205 field study cats died of the effusive form of feline infectious peritonitis. (See Adverse Reactions ) Persistent, progressive weight loss that resulted in hepatic lipidosis occurred in 2 of 205 cats on treatment with cyclosporine in field studies. Monitoring of body weight is recommended. (See Adverse Reactions )

Modulis® for Cats (cydosporine oral solution) USP Modified

Not for human use. Keep this and all drugs out of reach of children. For use only in dogs. Capsules should not be broken or opened. Wear gloves during administration. Wash hands after administration. In case of accidental ingestion, seek medical advice immediately and provide the package insert or the label to the physician.

Sporimune™ (cyclosporine capsules) USP MODIFIED

Warnings: MODULIS® for Dogs (cyclosporine oral solution) is a systemic immunosuppressant that may increase the susceptibility to infection and the development of neoplasia.

Modulis® for Dogs (cyclosporine oral solution) USP MODIFIED 100 mg/mL

Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Keep this and all drugs out of reach of children.

Sporimune™ (cyclosporine capsules) USP MODIFIED

ATOPICA (cyclosporine) is a systemic immunosuppressant that may increase the susceptibility to infection and the development of neoplasia.

Atopica™

A total of 265 dogs were included in the field study safety analysis. One hundred and eleven (111) dogs were treated with placebo for the first 30 days. For the remainder of the study, all dogs received cyclosporine capsules. Fourteen dogs withdrew from the study due to adverse reactions. Four dogs withdrew from the study after vomiting. One dog each withdrew from the study after diarrhea; vomiting, diarrhea and pruritus; vomiting, depression and lethargy; lethargy, anorexia and hepatitis; gingival hyperplasia, lethargy, polyuria/polydipsia and soft stool; seizure; sebaceous cyst; pruritus; erythema; or otitis externa. Vomiting and diarrhea were the most common adverse reactions occurring during the study. In most cases, signs spontaneously resolved with continued dosing. In other cases, temporary dose modifications (brief interruption in dosing, divided dosing, or administration with a small amount of food) were employed to resolve signs. Persistent otitis externa, urinary tract infections, anorexia, gingival hyperplasia, lymphadenopathy and lethargy were the next most frequent adverse events observed. Gingival hyperplasia regressed with dose tapering. Owners of four dogs reported seizures while dogs were receiving cyclosporine. In one dog, seizures were the result of a brain tumor diagnosed one month into the study. Another dog experienced seizures before and after the study. Otitis externa, allergic otitis, or pinna erythema, with or without exudates, commonly accompanies atopy. Many dogs entered the study with otitis externa, which did not resolve without otic treatment. New cases of otitis externa, allergic otitis, or pinna erythema developed while dogs were receiving cyclosporine. However, the incidence rate was lower with cyclosporine compared to placebo. A change in the dose frequency was not necessary when new cases occurred. Number of Dogs Displaying Each Clinical Observation in the Field Study Clinical sign % out of 265 Vomiting 30.9% Diarrhea 20.0% Persistent Otitis Externa 6.8% Urinary Tract Infection 3.8% Anorexia 3.0% Lethargy 2.3% Gingival Hyperplasia 2.3% Lymphadenopathy 2.3% The following clinical signs were reported in less than 2% of dogs treated with cyclosporine in the field study: constipation, flatulence, Clostridial organisms in the feces, nausea, regurgitation, polyuria/polydipsia, strong urine odor, proteinuria, pruritus, erythema/flushed appearance, pyoderma, sebaceous adenitis, crusty dermatitis, excessive shedding, coarse coat, alopecia, papillomas, histiocytoma, granulomatous mass or lesion, cutaneous cyst, epulis, benign epithelial tumor, multiple hemangioma, raised nodule on pinna, seizure, shaking/trembling, hind limb twitch, panting, depression, irritability, hyperactivity, quieter, increased light sensitivity, reluctance to go outside, weight loss, hepatitis. The following clinical signs were observed in 1.5-4.5% of dogs while receiving the placebo: vomiting, diarrhea and urinary tract infection. The following clinical signs were observed in less than 1% of dogs receiving the placebo: anorexia, otitis externa, cutaneous cysts, corneal opacity, lymphadenopathy, erythema/flushed appearance. Clinical Pathology Changes: During the study, some dogs experienced changes in clinical chemistry parameters while receiving cyclosporine, as described in the following table: Clinical Chemistry % Affected (out of 265) Elevated Creatinine 7.8% Hyperglobulinemia 6.4% Hyperphosphatemia 5.3% Hyperproteinemia 3.4% Hypercholesterolemia 2.6% Hypoalbuminemia 2.3% Hypocalcemia 2.3% Elevated BUN 2.3% In addition, the following changes in clinical chemistry parameters were noted in less than 2% of dogs: hypernatremia; hyperkalemia, elevated ALT, elevated ALP, hypercalcemia and hyperchloremia. These clinical pathology changes were generally not associated with clinical signs. POST-APPROVAL EXPERIENCE: The following adverse events are based on post-approval adverse drug experience reporting. Not all adverse reactions are reported to FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data. The following adverse events are grouped by body system and are presented in decreasing order of reporting frequency. Gastrointestinal: Emesis, diarrhea, gingival hyperplasia, hemorrhagic diarrhea, abdominal pain, hematemesis, digestive tract hemorrhage, hypersalivation, retching, flatulence, tenesmus, intestinal stasis, digestive tract hypermotility, melena, pancreatitis, involuntary defecation General: Lethargy, anorexia, weight loss, polydipsia, hyperthermia, pale mucous membrane, general pain, collapse, dehydration, edema Dermatologic: Pruritus, dermatitis and eczema, alopecia, erythema, papilloma, bacterial skin infection, skin lesion, skin and/or appendage neoplasm, pigmentation disorder, hair change, hyperkeratosis, histiocytoma, fungal skin infection, dermal cyst(s), desquamation Behavioral: Hyperactivity, behavioral changes, anxiety, vocalization, aggression, inappropriate urination, disorientation Neurologic: Muscle tremor, convulsion, ataxia, paresis Respiratory: Tachypnea, dyspnea, cough Urologic: Polyuria, urine abnormalities (hematuria, urinary tract infection, proteinuria, glucosuria, decreased urine concentration) urinary incontinence, cystitis, renal failure, renal insufficiency Immune: Urticaria, anaphylaxis, allergic edema Blood and lymphatic: Lymphadenopathy, anemia, hypoalbuminemia, leukopenia Hepatic: Elevated Liver Enzymes, hepatopathy, hepatomegaly, hepatitis Musculoskeletal: Lameness, limb weakness, myositis Ear and labyrinth: Otitis externa Cardio-vascular: Tachycardia Endocrine: Diabetes mellitus, hyperglycemia In some cases, death/euthanasia has been reported as an outcome of the adverse events listed above. Neoplasms have been reported in dogs taking cyclosporine, including reports of lymphoma/lymphosarcoma and mast cell tumor. It is unknown if these were preexisting or developed de novo while on cyclosporine. Diabetes mellitus has been reported; West Highland White Terriers are the most frequently reported breed. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Virbac AH, Inc. at 1-800-338-3659 or us.virbac.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.

CYCLAVANCE® (cyclosporine oral solution) USP MODIFIED

Adverse Reactions: A total of 265 dogs were included in the field study safety analysis. One hundred and eleven (111) dogs were treated with placebo for the first 30 days. For the remainder of the study, all dogs received cyclosporine capsules. Fourteen dogs withdrew from the study due to adverse reactions. Four dogs withdrew from the study after vomiting. One dog each withdrew from the study after diarrhea; vomiting, diarrhea and pruritus; vomiting, depression and lethargy; lethargy, anorexia and hepatitis; gingival hyperplasia, lethargy, polyuria/polydipsia and soft stool; seizure; sebaceous cyst; pruritus; erythema; or otitis externa. Vomiting and diarrhea were the most common adverse reactions occurring during the study. In most cases, signs spontaneously resolved with continued dosing. In other cases, temporary dose modifications (brief interruption in dosing, divided dosing, or administration with a small amount of food) were employed to resolve signs. Persistent otitis externa, urinary tract infections, anorexia, gingival hyperplasia, lymphadenopathy and lethargy were the next most frequent adverse events observed. Gingival hyperplasia regressed with dose tapering. Owners of four dogs reported seizures while dogs were receiving cyclosporine. In one dog, seizures were the result of a brain tumor diagnosed one month into the study. Another dog experienced seizures before and after the study. Otitis externa, allergic otitis, or pinna erythema, with or without exudates, commonly accompanies atopy. Many dogs entered the study with otitis externa, which did not resolve without otic treatment. New cases of otitis externa, allergic otitis, or pinna erythema developed while dogs were receiving cyclosporine. However, the incidence rate was lower with cyclosporine compared to placebo. A change in the dose frequency was not necessary when new cases occurred. Number of Dogs Displaying Each Clinical Observation in the Field Study Clinical Sign % out of 265 Vomiting 30.9% Diarrhea 20.0% Persistent Otitis Externa 6.8% Urinary Tract Infection 3.8% Anorexia 3.0% Lethargy 2.3% Gingival Hyperplasia 2.3% Lymphadenopathy 2.3% The following clinical signs were reported in less than 2% of dogs treated with cyclosporine in the field study: constipation, flatulence, Clostridial organisms in the feces, nausea, regurgitation, polyuria/polydipsia, strong urine odor, proteinuria, pruritus, erythema/flushed appearance, pyoderma, sebaceous adenitis, crusty dermatitis, excessive shedding, coarse coat, alopecia, papillomas, histiocytoma, granulomatous mass or lesion, cutaneous cyst, epulis, benign epithelial tumor, multiple hemangioma, raised nodule on pinna, seizure, shaking/trembling, hind limb twitch, panting, depression, irritability, hyperactivity, quieter, increased light sensitivity, reluctance to go outside, weight loss, hepatitis. The following clinical signs were observed in 1.5-4.5% of dogs while receiving the placebo: vomiting, diarrhea and urinary tract infection. The following clinical signs were observed in less than 1% of dogs receiving the placebo: anorexia, otitis externa, cutaneous cysts, corneal opacity, lymphadenopathy, erythema/flushed appearance. Clinical Pathology Changes: During the study, some dogs experienced changes in clinical chemistry parameters while receiving cyclosporine, as described in the following table: Clinical Chemistry % Affected (out of 265) Elevated Creatinine 7.8% Hyperglobulinemia 6.4% Hyperphosphatemia 5.3% Hyperproteinemia 3.4% Hypercholesterolemia 2.6% Hypoalbuminemia 2.3% Hypocalcemia 2.3% Elevated BUN 2.3% In addition, the following changes in clinical chemistry parameters were noted in less than 2% of dogs: hypernatremia; hyperkalemia, elevated ALT, elevated ALP, hypercalcemia and hyperchloremia. These clinical pathology changes were generally not associated with clinical signs.

Modulis® for Dogs (cyclosporine oral solution) USP MODIFIED 100 mg/mL

The clinical safety of ATOPICA for Cats was assessed in a masked, controlled 6-week field study followed by a 12-week open-labeled dose-tapering field study. In these two field studies, 205 cats received treatment with ATOPICA for Cats for up to 126 days. Two cats died or were euthanized within two weeks following study exit. One cat was diagnosed with the effusive form of feline infectious peritonitis and died following normal study exit, and one cat with pre-existing anemia that worsened during the study was diagnosed with aplastic anemia and euthanized because of a poor prognosis for recovery. Fourteen of the 205 cats (6.8%) were withdrawn from the studies due to the occurrence of an adverse reaction. Adverse reactions in these 14 cats included weight loss, anorexia, vomiting, diarrhea, hypersalivation, lethargy, hepatic lipidosis and jaundice, upper respiratory signs, ocular discharge, cough, toxoplasmosis, lymphopenia, anemia, bacterial dermatitis, seizure, ataxia, and small cell gastrointestinal lymphoma. The most commonly reported adverse reaction was vomiting. In most cases, vomiting spontaneously resolved with continued dosing. Adverse reactions occurred most often with daily dosing compared to other dosing regimes. Adverse reactions reported with greater than 2% frequency in the two field studies. *Cats may have experienced more than one type or occurrence of a reaction during the studies. Adverse Reaction* Number (Percent) of Cases n = 205 Vomiting/Retching/Regurgitation 72 (35.1%) Weight Loss 42 (20.5%) Diarrhea 31 (15.1%) Anorexia/Decreased Appetite 29 (14.1%) Lethargy/Malaise 28 (13.6%) Hypersalivation 23 (11.2%) Behavioral Disorder (hiding, hyperactivity, aggression) 18 (8.8%) Ocular Discharge/Epiphora/Conjunctivitis 14 (6.8%) Sneezing/Rhinitis 11 (5.4%) Gingivitis/Gingival Hyperplasia 9 (4.4%) Polydipsia 6 (2.9%) The following adverse reactions were reported in less than or equal to 2% of cats treated with ATOPICA for Cats in the two field studies: bacterial dermatitis, hepatic lipidosis and jaundice, gastrointestinal small cell lymphoma, constipation, cough, toxoplasmosis, muscle wasting, muscle tremors, ataxia, convulsion, polyuria, urinary tract infection, inappropriate urination or defection, seborrhea, worsening otitis externa, papilloma, leukotrichia (whitening of hair) and excessive hair growth, anemia, lymphopenia, worsening monocytosis, worsening neutrophilia, hyperglobulinemia, increased serum creatinine and urea nitrogen, and increased alanine aminotransferase. Contact Information: To report suspected adverse drug events or for technical assistance, contact Elanco US Inc. at 1-888-545-5973. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae

Atopica™ for Cats (cyclosporine oral solution) USP MODIFIED 100 mg/mL

ADVERSE REACTIONS: In the KCS clinical field trial, there were 20 adverse reactions reported out of 132 cases enrolled. This corresponds to an adverse reaction rate of 12.9% (13 of 101 cases) for OPTIMMUNE Ophthalmic Ointment treated dogs and 22.6% (7 of 31) for placebo treated dogs. The reactions described were primarily ocular and periocular inflammatory reactions. These were likely a function of therapy being unable to fully control the keratoconjunctivitis, rather than a true "adverse reaction." Similarly, in the CSK trial, of 36 cases evaluated for safety, adverse reactions were noted in 2 animals (5.6%). One involved transient hyperemia, epiphora, and mild discomfort of the eye. The other involved periocular/palpebral inflammation and mild alopecia. On rare occasion, instillation of OPTIMMUNE Ophthalmic Ointment may be associated with local irritation as manifested by periocular redness, lid spasm, and excessive rubbing. As the eyes of dogs with KCS often demonstrate considerable inflammation, it will be difficult to determine whether this local irritation constitutes a hypersensitivity to OPTIMMUNE Ophthalmic Ointment. If this ocular irritation persists beyond 7 days, hypersensitivity to a component of OPTIMMUNE Ophthalmic Ointment should be suspected and therapeutic options reassessed.

Optimmune® (0.2% Cyclosporine, USP) Ophthalmic Ointment

The initial dose of Cyclosporine Capsules, USP MODIFIED is 5 mg/kg/day (3.3-6.7 mg/kg/day) as a single daily dose for 30 days. Following the initial daily treatment period, the dose of Cyclosporine Capsules, USP MODIFIED may be tapered by decreasing the frequency of dosing to every other day or twice weekly, until a minimum frequency is reached which will maintain the desired therapeutic effect. Cyclosporine Capsules, USP MODIFIED should be given at least one hour before or two hours after a meal. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily.

Oral

Sporimune™

The initial dose is 5 mg/kg/day (3.3-6.7 mg/kg/day) as a single daily dose for 30 days. Following this initial daily treatment period, the dose may be tapered by decreasing the frequency of dosing to every other day or twice weekly, until a minimum frequency is reached which will maintain the desired therapeutic effect. Atopica® should be given at least one hour before or two hours after a meal. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily.

Oral

Federal law restricts this drug to use by or on the order of a licensed veterinarian.ATOPICA is contraindicated for use in dogs with a history of neoplasia.For use in dogs only.Capsules should not be broken or opened.

Atopica™

Administer 5 mg per kilogram (mg/kg) of body weight given orally as a single daily dose for 30 days. Following this initial daily treatment period, the dosage may be tapered by decreasing the frequency of administration to every other day or two times a week, until a minimum frequency is reached which will maintain the desired therapeutic effect.

Oral

Cyclavance®

Apply a 1/4 inch strip of ointment to the affected eye(s) every 12 hours.

Ophthalmic

Place ointment directly on cornea or into the conjunctival sac. For ophthalmic use in dogs only. Safety of use in puppies, pregnant or breeding animals has not been determined. US Federal law restricts thiis drug to use by or on the order of a licensed veterinarian.

Optimmune®

Dosage and Administration: Always provide the Instructions for Assembling the Dispensing System and Preparing a Dose of MODULIS® for Dogs and the Information for Dog Owners with prescription. The initial dose of MODULIS® for Dogs is 5 mg/kg/day as a single daily dose for 30 days. Following this initial daily treatment period, the dose of MODULIS® for Dogs may be tapered by decreasing the frequency of dosing to every other day or twice weekly, until a minimum frequency is reached which will maintain the desired therapeutic effect. MODULIS® for Dogs should be given at least one hour before or two hours after a meal. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily. The dispensing system includes oral dosing syringes to accompany MODULIS® for Dogs: - For dogs 4 lbs to 40 lbs, use the 1 mL syringe: The 1 mL syringe is graduated in 1 pound (lb) increments. To dose the dog, the syringe should be filled to the nearest 1 lb graduation corresponding to the dog's body weight in lbs (round down to the nearest whole lb if 0.1 to 0.4 lb, or round up to the nearest whole lb if 0.5 to 0.9 lb). Each 1-lb graduation on the 1 mL syringe delivers a volume of 0.023 mL, providing 2.3 mg/lb (5 mg/kg) dose. - For dogs 41 lbs to 125 lbs, use the 3 mL syringe: The 3 mL syringe is graduated in 5 pound (lb) increments. To dose the dog, the syringe should be filled to the nearest 5 lb graduation corresponding to the dog's body weight in lbs (round down to the nearest whole lb if 0.1 to 0.4 lb, or round up to the nearest whole lb if 0.5 to 0.9 lb). Each 5-lb graduation on the 3 mL syringe delivers a volume of 0.115 mL, providing 2.3 mg/lb (5 mg/kg) dose. Do not rinse or clean the oral dosing syringe between uses. Note: Always close the bottle with the child-resistant screw cap after each use. The 1 mL syringe is graduated in 1 lb increments corresponding to 0.023 mL/lb. This syringe is for dosing dogs 4 to 40 lb. The 1 mL syringe will be included with the 4.7, 15, and 30 mL bottles. The 3 mL syringe is graduated in 5 lb increments corresponding to 0.115 mL/5 lb. This syringe is for dosing dogs 41 to 125 lb. The 3 mL syringe will be included with the 30 and 50 mL bottles. (See Instructions for Assembling the Dispensing System and Preparing a Dose of MODULIS ® for Dogs)

ORAL

Modulis® for Dogs (cyclosporine oral solution) USP MODIFIED 100 mg/mL

Dosage and Administration: Always provide the Instructions for Assembling the Dispensing System and Preparing a Dose of MODULIS® for Cats and the Information for Cat Owners with prescription. The initial dose of MODULIS® for Cats is 3.2 mg/lb/day (7 mg/kg/day) as a single daily dose for a minimum of 4 to 6 weeks or until resolution of clinical signs. Following this initial daily treatment period, the dose of MODULIS® for Cats may be tapered by decreasing the frequency of dosing to every other day or twice weekly to maintain the desired therapeutic effect. MODULIS® for Cats should be administered directly on a small amount of food or orally just after feeding. Whenever possible, MODULIS® for Cats should be administered on a consistent schedule with regard to meals and time of day. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily. The dispensing system includes an oral dosing syringe graduated in 1 lb increments. To dose the cat, the syringe should be filled to the nearest 1 lb corresponding to the cat's body weight (round down if 0.1 to 0.4 lb, round up if 0.5 to 0.9 lb). Each pound graduation on the syringe delivers a volume of 0.032 mL providing 3.2 mg/lb. Do not rinse or clean the oral dosing syringe between uses. (See Instructions for Assembling the Dispensing System and Preparing a Dose of MODULIS ® for Cats)

ORAL

Modulis® for Cats (cydosporine oral solution) USP Modified

Always Provide the Instructions for Assembling the Dispensing System and Preparing a Dose of CYCLAVANCE and the Information for Dog Owners with the prescription. The initial dose of CYCLAVANCE is 5 mg/kg/day as a single daily dose for 30 days. Following this initial daily treatment period, the dose of CYCLAVANCE may be tapered by decreasing the frequency of dosing to every other day or twice weekly, until a minimum frequency is reached which will maintain the desired therapeutic effect. CYCLAVANCE should be given at least one hour before or two hours after a meal. If a dose is missed, the next dose should be administered (without doubling) as soon as possible but dosing should be no more frequent than once daily. The dispensing system for the 5 and 15 mL vial sizes includes a 1 mL oral dosing syringe graduated in 0.05 mL increments. To dose the dog, administer 0.05 mL of CYCLAVANCE per 2.2 lbs of body weight. The dispensing system for the 30 and 50 mL vial sizes includes both a 1 mL oral dosing syringe graduated in 0.05 mL increments, and a 3 mL oral dosing syringe graduated in 0.1 mL increments. To dose the dog, administer 0.1 mL of CYCLAVANCE per 4.4 lbs of body weight. Do not rinse or clean the oral dosing syringe between uses. (See Instructions for Assembling the Dispensing System and Preparing a Dose of CYCLAVANCE.)

ORAL

CYCLAVANCE® (cyclosporine oral solution) USP MODIFIED

DOSAGE AND ADMINISTRATION: Remove debris with suitable nonirritating solutions. Apply a 1/4-inch strip of ointment to the affected eye(s) every 12 hours. The ointment may be placed directly on the cornea or into the conjunctival sac. It is recommended that dogs exhibiting chronic recurring conjunctivitis be tested for adequate tear production to determine if they are suffering from early stages of chronic KCS. For best results in treating KCS, cyclosporine ophthalmic ointment should be administered early in the course of the disease before irreversible damage to the lacrimal tissue, dense corneal scarring, or pigmentation occurs. Dogs afflicted with KCS or CSK will most likely require lifelong consistent therapy (see EFFICACY section above). For CSK, because environmental factors such as ultraviolet (UV) radiation are implicated in the pathogenesis, clinical signs may subside in the winter months when light intensity is reduced or if the dog is moved to a lower altitude, or indoors, and thus exposed to less UV radiation.1 In cases refractory to cyclosporine, the diagnosis should be reevaluated and a different course of therapy considered. Periodic reassessment of the need for OPTIMMUNE Ophthalmic Ointment therapy is recommended.

OPHTHALMIC

Optimmune® (0.2% Cyclosporine, USP) Ophthalmic Ointment

The initial dose of Sporimune is 5 mg/kg/day (3.3-6.7 mg/kg/day) as a single daily dose for 30 days. Following this initial daily treatment period, the dose of Sporimune may be tapered by decreasing the frequency of dosing to every other day or twice weekly, until a minimum frequency is reached which will maintain the desired therapeutic effect. Sporimune should be given at least one hour before or two hours after a meal. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily. Dose Administration Dog body weight (lbs) Dog body weight (kg) Dose 5 mg/kg 4 – 6.5 lbs 2 – 2.9 kg 10 mg capsule 6.6 – 9 lbs 3 – 3.9 kg 2 × 10 mg capsules 9.1 – 16 lbs 4 – 7.9 kg 25 mg capsule 16.1 – 33 lbs 8 – 14.9 kg 50 mg capsule 33.1 – 64 lbs 15 – 28.9 kg 100 mg capsule 64.1 – 79 lbs 29 – 35.9 kg 100 mg capsule +50 mg capsule 79.1 – 121 lbs 36 – 55.9 kg 2 × 100 mg capsules

ORAL

Sporimune™ (cyclosporine capsules) USP MODIFIED