Contraindications if the dog: 
• is on aspirin therapy, 
• has liver disease, 
• has kidney disease, 
• has heart disease, 
• has lung disease, or 
• has a hormonal disease. 
• He may not be able to take methazolamide, or he may require a lower dose or special monitoring during treatment if he have any of the conditions listed above. 

Give methazolamide with food if it upsets his stomach. 
• Store methazolamide at room temperature away from moisture and heat. 
• Symptoms of a methazolamide overdose include drowsiness, decreased appetite, nausea, vomiting, dizziness, numbness or tingling, shaking, and ringing in the ears. 

cyclosporine (Sandimmune, Optimmune). Cyclosporine may have more side effects if it is taken with methazolamide. 

primidone (Mysoline). Primidone may not be as effective if it is taken with methazolamide, and seizure control may be reduced. 

diflunisal (Dolobid). Diflunisal may increase both the activity and the side effects of methazolamide. 
aspirin (Disalcid, Amigesic, Argesic-SA, Salflex, Salsitab, others), choline salicylate  
magnesium salicylate (Doan's, Magan, Mobidin), and other aspirin-like products (salicylates).

These medicines may also interact with methazolamide, and special monitoring of therapy may be necessary. 
lithium (Lithobid, Eskalith, others). methazolamide may decrease the level of lithium in his blood. Special monitoring or a dosage adjustment may be necessary. 

• Drugs other than those listed here may also interact with methazolamide. Talk to your vet and pharmacist before giving any prescription or over-the-counter medicines. 

Adverse Reactions 
>10%: Central nervous system: Malaise 
Gastrointestinal: Metallic taste, anorexia 
Genitourinary: Polyuria 
Neuromuscular & skeletal: Weakness 

1% to 10%: Central nervous system: Mental depression, drowsiness, dizziness  Genitourinary: Crystalluria 

<1%: Fever, headache, seizures, fatigue, rash, sulfonamide rash, Stevens-Johnson syndrome, hyperchloremic metabolic acidosis, hypokalemia, hyperglycemia, GI irritation, constipation, xerostomia, black tarry stools, bone marrow suppression, dysuria, paresthesia, trembling, unsteadiness, myopia, tinnitus, loss of smell, hypersensitivity 

Pharmacodynamics/Kinetics
Onset of action: Slow in comparison with acetazolamide (2-4 hours) 
Peak effect: 6-8 hours 
Duration: 10-18 hours 
Absorption: Slowly from GI tract 
Distribution: Distributes well into tissue 
Protein binding: ~55% 
Half-life: ~14 hours 
Elimination: ~25% excreted unchanged in urine

Medical Therapy for Glaucoma

Currently, five classes of drug are available for use in patients with glaucoma or elevated intraocular pressure. No perfect medicine has been developed - all have some side-effects. Moreover, in some patients, medication fails to reduce IOP adequately. It is important therefore to balance efficacy, tolerability and side effects on a patient-by-patient basis. 

The treatment program can change over the time that glaucoma is treated. In some cases the change is necessary because of an unwanted side effect from the medication. In other cases, prescribing a stronger drug or adding another medication is necessary to maintain control of the eye pressure. 

Carbonic Anhydrase Inhibitors also lower pressure in the eye by decreasing aqueous production. Carbonic anhydrase inhibitors are available as topically (dorzolamide and brinzolamide) or orally (acetazolamide, methazolamide). The topical forms are associated with fewer systemic side-effects than the oral forms and are better tolerated by many patients.

Alcon recently introduced AZOPT® (brinzolamide) ophthalmic suspension 1%. Methazolamide is also called "Neptazane". Daranide is another similar oral medication that seems to have fewer side effects for many dogs so it's something you might want to ask about. In Canada, I know that when Melody (Kerry's dog) was on Neptazane, Daranide wasn't available here. 

As for dosage, Melody was on 50 mg twice a day, and we reduced it to 25 mg, then to 12.5 mg, but at that dosage it didn't do much for her. However, remember that Melody was an 80 lb Samoyed, and it's given by weight. I'm not sure of the dosage for a little dog, but the vet would know of course.

Neptazane is a fairly strong oral medication - it does work quite well but you want to have your dog  on the lowest dose that works. You may notice her panting a bit - that's a fairly common side effect. My vet explained it as being like when a marathon runner hits the wall - same type of effect on the dog.

Giving her 12.5 mg at night should help her eye, and not cause her problems. And especially since at night she's sleeping and not active (and also because she has those flare-ups at night.

I'm glad the vet agreed with me about the night-time being worse because of dilation of the pupil from darkness. I used to keep Melody in the brightest light I could, until we put her on Xalatan eyedrops at night which constricted her pupils. The Neptazane we only used when her pressures were up, then slowly tried to reduce it to a level where the pressure was staying within normal range (under Dr.'s instructions of course). I'm also glad he agreed with you that you should stop the Trusopt!

Optimmune® OPHTHALMIC OINTMENT (0.2% CYCLOSPORINE, USP)

INDICATIONS: OPTIMMUNE Ophthalmic Ointment is indicated for the management of chronic keratoconjunctivitis sicca (KCS) and chronic superfical keratitis (CSK) in dogs.
DOSAGE AND ADMINISTRATION:Remove debris with suitable non-irritating solutions. Apply approximately 1/4 inch strip of ointment to the affected eye(s) every 12 hours.
HOW SUPPLIED: Box of 6 x 3.5 gm tube. 

Full Product Information 

Optimmune® OPHTHALMIC OINTMENT (0.2% CYCLOSPORINE, USP)

For ophthalmic use in dogs only. Sterile 

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

DESCRIPTION: Each gram of OPTIMMUNE Ophthalmic Ointment contains 2 mg of  cyclosporine, USP; petrolatum, USP; corn oil, NF; and Amerchol¨ CAB base. Cyclosporine (cyclosporin A), the active ingredient of OPTIMMUNE Ophthalmic Ointment, is a cyclic undecapeptide metabolite of the fungus Tolypocladium inflatum gams.

MODE OF ACTION: When applied opthalmically, cyclosporine is believed to act as a local immunomodulator of diseases suspected to be immune-mediated such as keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK). In the management of KCS, the mechanism by which cyclosporine causes an increase in lacrimation is poorly understood. Clinical improvement in cases of KCS is not necessarily dependent on an increase in aqueous tear production (as measured by the Schirmer Tear Test (STT)). See EFFICACY. 

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

PRECAUTIONS: The clinical effect of OPTIMMUNE Ophthalmic Ointment have not been determined in dogs with KCS due to the following conditions: congenital alacrima, sulfonamide usage, canine distemper virus, metabolic disease, surgical removal of the third eyelid gland, and facial nerve paralysis with loss of the palpebral reflex. Some of the underlying conditions which may lead to KCS can be either transient (eg, facial nerve trauma) or correctable with appropriate treatment. Consequently recovery from clinical signs attributed to KCS may be observed and treatment options may need reconsideration.

When switching to cyclosporine from another therapeutic agent (eg, frequent application of an artificial tear preparation) for KCS or CSK, it should be kept in mind that clinical efficacy is not necessarily apparent immediately after initiation of OPTIMMUNE Ophthalmic Ointment therapy. Several days to a few weeks may be required before the clinical effects of OPTIMMUNE Ophthalmic Ointment are of sufficient magnitude such that previously initiated therapy can be safely withdrawn. Abrupt cessation of a therapeutic agent immediately upon initiation of OPTIMMUNE Ophthalmic Ointment therapy can result in rapid clinical relapse which may be erroneously interpreted as an adverse reaction to OPTIMMUNE Ophthalmic
Ointment.

The safety of OPTIMMUNE Ophthalmic Ointment has not been determined in cases of preexisting viral or fungal ocular infections. It is recommended that in such cases, OPTIMMUNE Ophthalmic Ointment therapy be delayed until the fungal/viral ocular infection has been successfully treated.

The safety of OPTIMMUNE Ophthalmic Ointment in puppies, pregnant bitches, or dogs used for breeding has not been determined.

EFFICACY: 1.KCS A well-controlled clinical field trial was conducted by veterinary ophthalmologists in 9 states and included 132 dogs afflicted with KCS of which 124 were evaluated for efficacy. Dogs were randomly assigned to BID treatment with either 0.2% (OPTIMMUNE Ophthalmic Ointment ) or 0% (placebo vehicle) cyclosporine ophthalmic ointment for 12 weeks. Treatment with OPTIMMUNE Ophthalmic Ointment resulted in an average 8 to 9 mm increase in STT by the end of the study period (vs 3 to 4 mm for the placebo vehicle). Most of the increase in STT, approximately 6 mm, occurred in the first week of therapy. Some dogs improved clinically (ie, exhibited a decrease in conjunctival and/or corneal pathology) without an increase in STT values. This is thought to occur through suppression of inflammation by cyclosporine on the pouler surface. In this clinical field trial, OPTIMMUNE Ophthalmic Ointment therapy was also associated with an improvement in clinical signs in comparison to the placebo. Blepharitis, blepharospasm, and "other signs of ocular discomfort" (eg, pawing at eyes), were markedly reduced. Improvement in conjunctival health as manifested by reduced conjunctival hypertrophy, reduced hyperemia, reduced conjunctival discharge volume, and improved character of discharge was evident. Improvement in corneal health as manifested by improved corneal surface contour, reduced corneal edema and corneal neovascularization was also noted. Overall improvement was noted in 81% of eyes treated with OPTIMMUNE Ophthalmic Ointment.

Withdrawal of OPTIMMUNE Ophthalmic Ointment therapy resulted in rapid clinical regression in all but one test eye indicating the need for long-term continual therapy for almost all cases of chronic KCS.


2.CSK The efficacy of Optimmune® Ophthalmic Ointment was determined in a historical controlled clinical field trial conducted by veterinary ophthalmologists in four countries and included 36 dogs afflicted with CSK (German shepherd pannus), were treated twice daily with OPTIMMUNE Ophthalmic Ointment for 6 weeks. Clinical improvement was noted by the
investigators in 90.3% of eyes treated with OPTIMMUNE Ophthalmic Ointment when compared to baseline.

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.

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 keratoconjuntivitis, rather than a true “adverse reaction.”" Simiarly, in the CSK trial, of 35 cases evaluated for safety, adverse reactions were noted in 2 animals (5.6%). One involved translent 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 option reassessed.

DOSAGE AND ADMINISTRATION: Remove debris with suitable nonirritating solution. 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, or 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 radiation1.

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. 

HOW SUPPLIED: OPTIMMUNE Ophthalmic Ointment is available in a 3.5 gm tube, carton of 6, NDC 0061-1088-01.

STORAGE CONDITIONS: Store between 2° and 30°C (36° and 86°F).

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.
June 1995

REFERENCE: 1 Roberts, Steven M. Pannus. in: Kirk's Current Veterinary
Therapy XII, Small Animal Practice. Philadelphia: W.B. Saunders Co:
1995:1245-1248.

ACULAR (R) (ketorolac tromethamine) is a member of the pyrrolo-pyrolle group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. 

Acular-PF (ketorolac)- This new preservative-free formulation (Acular-PF) has been developed to provide the activity og the original formulation of Acular without the possibility of developing preservative-induced ocular sensitivity. 

How it Works
Ketorolac is a nonsteroidal antiinflammatory drug (NSAID) with analgesic and antiinflammatory activity that is belived to be due to its abaility to inhibit prostaglandin biosynthesis.. 

Clinical Tips
Only small amounts of the drug are absorbed following ocular administration, with blood levels being less 3% of those following a systemic dose. When given systemically, it does not cause pupil constriction. It has no effect on intraocular pressure when given in the eye. Patients senitive to aspirin, phenylacetic acid derivatives or oher NSAIDs may be cross-senitive to ketorolac. The drug should be used with caution in patients with known bleeding tendencioes or in patients who are receiving other drugs known to prolong bleeding time. The most common adverse events have been transient stinging and burning on instillation (seen in about 20% of patients). The useual dose is one drop four times a day in the operated eye as needed for pain and photophobia for up to 3 days after incisional refractive surgery. 

This eyedrop is also now used for post-surgical inflammation following cataract extraction. Acular (ketorolac tromethamine ophthalmic solution 0.5%) works by inhibiting prostaglandins in the aqueous humor.