Overview of FIV and Gingivostomatitis: Medications and Supplements

Many of the medications and supplements listed below have multiple functions. The attempt is made to place them in the category where they best fit. Information relating to dosage and administration reflects individual research sources and may not be those preferred by vets in actual clinical practice. This list of agents does not constitute a recommendation for use without veterinary guidance.

1. Antibiotics

Numerous antibiotics are used with some some success to treat oral infection, among them azithromycin and amoxicillin clavulanate. Convenia (Cefovecin sodium) has the advantage of 14-day action without the pain or stress of oral administration. However, following are the three that research sources and personal testimonies most often single out as antibiotics of choice for treatment of LPGS, in part because each has actions that go beyond bacteriocidal.

Clindamycin

Rationale: Possesses superior penetration of hard tissue and particular effectiveness agains anaerobes of the sort that are common in infections of teeth, bone, and joints.

Dosage: 5 mg/kg bid [Bellows]. 5-10mg/kg [Common]. Pulse dosing sometimes done for maintenance (e.g., one week out of four ).

Administration: Available as liquid or capsule. Liquid is bitter.

Cautions/Comments: For use beyond one month the manufacturer recommends monitoring liver and kidney function and doing blood counts.

Metronidazole

Rationale: Effective against anaerobic bacteria characteristic of oral disease and has additional anti-inflammatory action.

Dosage: 23 mg/lb sid [Roby, suggested particularly for LPGS]; 12.5 mg/kg sid [Chandler et al, Feline Medicine and Therapeutics]

Administration: Liquid or capsule. Taste is notoriously bad.

Cautions/Comments: Metronidazole has numerous drug interactions: with cimetidine, phenobarbitol, blood thinners (possibly pentoxifylline), etc. Some people report success with metronidazole. Addie, who prefers clindamycin, advises against it. ". . . metronidazole has a suppressant effect on cell mediated immunity in mice, and may be less desirable in this condition where CMI is preferable to the humoral response" [Addie] Since skewed cell-mediated immune response is believed to be involved with this disease, as well as humoral response, this may or may not be good advice.

Doxycycline

Rationale: Doxycycline has a history of effectiveness in treating periodontal disease, possibly through its ability to block the inflammatory effect of collagenase( an enzyme belonging to the class of matrix metalloproteinases (MMPs)), which can degrade collagen in bone and teeth. Teaming with niacinamide may provide added therapeutic benefit. Doxycycline also has analgesic properties.

Dosage: 10 mg/kg bid [unverified dosage]

Administration: It is particularly important to wash down doxycycline capsules with water since damage to the esophagus is possible if capsules fail to reach the stomach before opening.

Caution/Comments: "Tetracycline and niacinamide may be used to treat refractory autoimmune diseases. . . . It is not known how this combination works, but it seems to be unrelated to the antibiotic action of tetracycline. The two medications are given three times a day for 3 months, twice a day for two months, then once a day for one month" [Roby]. This dosage advice is for diseases such as pemphigus and discoid lupus. The success achieved in treatment of LPGS may be owing in part to effective action against the autoimmune component of the disease. Tetracycline is a more difficult drug for cats than doxycycline. Success reported with the combination of doxycycline and niacinamide.

2. Antivirals

L-Lysine

Rationale: L-lysine inhibits replication of feline herpesvirus

Dosage: 500mg bid for acute symptoms; 250 mg daily for maintenance

Administration: L-lysine is slightly salty but tasteless and is easily added to food

Cautions/Comments: L-lysine cannot be expected to be of use in the absence of chronic herpesvirus infection as an inciting factor in the oral disease.

Zinc

Rationale: Zinc has shown direct antiviral action agains human herpes virus and the common cold. It has also accelerated healing of human apthous stomatitis.

Dosage: 7-10mg daily [Addie]

Administration: Can be added to food; zinc ascorbate is also available as an oral spray to be used several times daily. Some products combine zinc with chlorhexidine as part of dental prophylaxis regimens. Maxiguard gel contains zinc ascorbate.

Cautions/Comments: Zinc should not be given concurrently with many medications, including antibiotics. The recommended dosage might not be appropriate for long-term use since zinc can cause a gradual leaching of other minerals, such as iron and copper.

Antiretrovirals

Rationale: Since the precise role of FIV in oral inflammatory disease is unknown, the basis of the effectiveness of antiretroviral drugs is unclear, but there is ample evidence in AZT-FIV studies that lowering viral burden can produce clinical improvement in oral inflammatory disease.

Dosage: AZT 5mg/kg bid; 3TC 3.75mg/kg bid; PMPA 12.5 mg/kg sid; FTC 5.5 mg/kg sid

Administration: 3TC available as liquids; others must be given as tablet or capsule

Cautions/Comments: Dosage of antiretroviral drugs cannot be missed. AZT must be monitored for anemia; PMPA should be monitored for kidney function

3. Anti-Inflammatories

Anti-inflammatories generally relieve pain as well as inflammation. Non-anti-inflammatory pain relievers are noted under "Pain Management"

Non-steroidal

Nonsteroidal anti-inflammatories allow avoidance of steroidal-specific side-effects, such as diabetes and symptom rebound, but may not be as effective and have side effects of their own. Because the cat’s liver does not have enough of a specific enzyme (bilirubin-glucuronide), NSAIDs tend to linger in the cat’s blood stream. So NSAIDs must be given in very limited doses and less frequently than to humans. Their principal mode of action is to block prostaglandin production by binding and inhibiting cyclooxygenase (COX). While the result of this effect is mainly a reduction in inflammation and peripheral nociceptor sensitization, there is some evidence that NSAID’s have a central analgesic action as well, though the exact mechanism remains unclear [Thompson].

Aspirin

Rationale: Relief from pain and inflammation. Aspirin is a nonselective COX-1/COX-2 inhibitor. A Danish study has found aspirin moderately safe and effective for relief of pain and inflammation due to LPGS.

Dosage: 10-25 mg/kg every other day [Addie]; (Non-specific use) 5mg/lb every other day or one 81 mg baby aspirin every three days [Roby]. The Danish study above concludes with a recommendation that aspirin can be safely administered every 48 hours for ten days. Danish study used sodium salicylate, which is preferable to baby aspirin.

Administration: Dividing baby aspirin is the common mode of administration. Give with food to avoid gastric upset.

Cautions/Comments: Unregulated use can cause kidney and liver damage, gastric damage, coma and death due to aspirin toxicity.

*Bonjela Gel

Rationale: A teething gel also used for oral ulcers, manufactured in the UK. Salicylates are anti-inflammatory with aspirin-like action. Also contains Cetalkonium, which has plaque prevention capacity.

Dosage: 1–2cm q3h.

Administration: One type of use suggests an actual therapeutic activity: "the gel was rubbed into the fauces and gums once a week for several weeks" [Cebuliak]; another suggests purely analgesic activity [R Malik, Private communication].

Cautions/Comments: As with aspirin, salicylates are potentially toxic, so should not be used excessively. "Richard Malik has recently endorsed his support of this product (choline salicylate,cetalkonium cholride, Reckitt and Coleman Pahrmaceuticals UK) the gel was rubbed into the fauces and gums once a week for several weeks. The cat also had caudal mouth extractions and had prednisolone and doxycycline"[Cebuliak].

Meloxicam [Metacam]

Rationale: A COX-2 inhibitor. COX-2 inhibitors were developed to mute pain and inflammation but to avoid the GI complications of COX-1 inhibitors. Licensed for one-time injectable use in cats but frequently used orally.

Dosage: Day 1: 0.3mg/kg po sid with food, Days 2-7: 0.1mg/kg sid with food [Addie]; 0.1 mg/kg SID for 3-5 days, then 0.1 mg/CAT/q 24-72 hours long-term [Thompson].

Administration: Available as injectable liquid or oral suspension. Easy to administer orally since only a drop or two is required as maintenance dosage. Manufacturers recommend every other day dosing when used as maintenance. Oral dosage for cats is off-label.

Cautions/ Comments: A recent arthritis study involved daily dosing of 40 senior cats at .01 to .03 mg/kg sid for nearly six months with a complete absence of serious side effects and only a small incidence of GI upset [Gunew]. This dosage is far less, however, than other recorded standard dosages. Among professionals and pet owner, use of this NSAID in cats is a subject of disagreement. Addie, while admitting that she has been unable to dispense with steroids entirely, promotes use of Metacam/Meloxicam to the maximum extent possible: "preferable to steroids in the control of this condition. In our study, both controls and the IFN omega group were put onto Metacam." Professionals are variously distrustful or dismissive regarding safety. Similarly, some pet owners report cats responding with negative side effects, sometimes dramatic; others report no side effects. Many pet owners prefer term limited dosing. Characterized as "well tolerated," but long-term dosage should be "carefully monitored" [Thompson]. Repeating injections can be extremely dangerous, and oral dosage should be conservative.

Ketoprofen

Rationale: One of the propionic acid class of non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects. Like other NSAIDs, acts by inhibiting the body's production of prostaglandin.

Dosage: 2 mg/kg [Robertson]; 1 mg/kg for 5 days [Addie]

Administration: Injectible (IV or IM) & Oral. (Comes in capsule only)

Cautions/Comments: Short term use has few side effects. As with some other NSAIDS and cats, kidney and liver damage and GI distress can occur with unregulated longer term use. Injectible form labeled for 5 day use. Metacam/meloxicam said by some to be more suitable for longer term use, although ketoprofen is used longer term [Hines]

Steroidal

The two main products in inflammation, Prostaglandins and Leukotrienes, are inhibited by the action of Glucocorticoids (i.e., steroids). Gluciocorticoids are immunosuppressive, suppressing cell-mediated immunity and antibody synthesis and also inhibiting aspects of natural immunity. There are many forms of steroids in many formulations and dosages. Following are those most commonly used to treat LPGS

Prednisolone

Rationale: Established in trials as superior to prednisone for use in cats. A short-acting steroid, closely akin to natural cortisol but more potent.

Dosage: [Oral] 2 mg/kg sid initially; then bid [Bellows]; ratchet down to lowest effective dose.

Administration: Available as a 5 mg tab and in various solutions for injection IM

Cautions/Comments: More prone to cause sodium retention (and therefore hypertension), but fewer side effects than more potent synthetic steroids.

Dexamethasone

Rationale: A synthetic steroid, longer-acting than prednisolone, practically devoid of sodium retention properties.

Dosage: oral .03-.07 mg/kg daily (or bid) depending on severity, lowered to .02 mg/kg maintenance [Baird]; .1 mg/kg daily[Dentalvets]

Administration: Available as tablet in dosages starting at .25 mg and liquid at 5 mg/ml; injectible 24 mg/ml [Roby]

Cautions/Comments: A more potent steroid than prednisolone. Can administer the injectible form of dexamethasone orally ( e.g.,compounded with fish-flavor).

Methylprednisolone Acetate [Depo-Medrol]

Rationale: A long-acting, synthetic steroid

Dosage: 20mg/cat every three to four weeks [Carmichael]; 2.5mg/lb [Roby] ; 2 mg/kg up to 20mg at intervals of 2-3 weeks for 3-6 treatments, then every 6 weeks [Dentalvets]

Administration: Available as 20 mg/ and 40mg/ml injectible. Given SubQ or IM. IM preferred.

Cautions/Comments: Not to be confused with Medrol, a short-acting version intended for oral admin.

Glucocorticoids Generally

Issues: There is no unanimous choice when it comes the question of whether to use short-acting or long-acting steroids. "One study found methylprdnisolone acetate . . . to be the most effective form of corticoid short term. . . . One can also use immunosuppressive doses of prednisolone . . . in divided doses initially but some sources report a less predictable control than using injectable depot corticoids' [Dentalvets]. Short-acting steroids have several advantages: dosage adjustment can be quickly and easily made, and there is no worry about injection site sarcoma. Some vets believe that there is a smaller risk of diabetes from short-acting steroids. Long-acting steroids have the advantage of not stressing a cat with a painful mouth by introducing tablets or liquids. When injection is the chosen route, long-acting steroids have the advantage of being less stressful and demanding than frequent injections and less likely than frequent injections of short-acting steroids to cause injection site sarcoma. Niels Pederson has been reported as ascribing maximum effect to frequent injections (of dexamethasone): "Dr. Pedersen at UCD recommends dexamethasone injections (SQ I am pretty sure), I think almost daily, for cats w/ calici virus related gingivitis/stomatitis, when nothing else works" [Sharon Johnston, Private communication]. Another source has noted that dexamethasone has been used in cases refractory to prednisolone" [Dentalvets]. A cat with poor intestinal absorption might well require injections rather than oral admin.

Cautions/Comments: [The Merck Veterinary Manual] " Repeated injections (methylprednisolone) or oral maintenance therapy (prednisone) are frequently required, as the treatment becomes progressively less effective and eventually completely ineffective. In addition, animals treated with glucocorticoids have a poorer prognosis once the teeth are extracted." [Addie] " . . .high rate of diabetes mellitus development following long term therapy, the risk of obesity and because whilst they appear to help the cat initially, there is a bounce-back effect - with the cat re-presenting with worse clinical signs than initially and requiring higher and higher doses just to maintain. Corticosteroids suppress both humoral and cell-mediated immunity, reducing the cat's chance of clearing the infection, and cause thinning of the epithelium."

4. Herbals

Aloe

Rationale: Established anti-inflammatory activity and history of use to treat apthous stomatitis in humans. As an immune enhancer increases monocyte response to alloantigens and stimulates cytotoxic T cell activity.

Dosage: No information

Administration: Available in various formulations, mostly as a hydrogel. Applied topically to oral tissue

Cautions/Comments: Acemannan was originally approved as a treatment for apthous stomatitis. Pure aloe and most of its various formulations are safe and nontoxic. One source suggests using aloe hydrogel as a base for a lactoferrin-containing "toothpaste." Also, recommended as part of a feline omega interferon treatment regimen [Mihaljevic].

Curcumin [Turmeric]

Rationale: Established anti-inflammatory activity and history of use to treat aphthous ulcers and oral mucositis in humans. Anti-inflammatory effect may be via inhibition of arachidonic acid metabolism. Also an anti-oxidant and inhibitor of lipid peroxidation.

Dosage: No confirmed dosage but reports of effect at 62.5mg bid

Administration: Likely mode of action is topical [Kato] rather than systemic. Does not have strong taste and may be added to food.

Cautions/Comments: Synergy reported in treatment of human mucositis when combined with Vitamin E and sunflower oil. Ulcerogenic threshold set at 100mg/kg in rats [Prasad]. If not added to food, should be administered when food will be in stomach.

Slippery Elm

Rationale: Widely used by humans with inflammatory bowel disease and has been shown to have antioxidant effects on mucosae in vitro.

Dosage: 600mg. daily ("The product I have been using is: Phytoplex Slippery Elm' produced by: Animal Alternatives, PO Box 289, Richmond, Surrey, TW10 7HX, England, UK. I must stress that I have no association whatsoever with this company and am not on a commission. Each tablet contains: 400.0mg Slippery Elm Bark; 0.001ml Cinnamon Oil BP; 0.001ml Clove Oil BP; 0.001ml Peppermint Oil BP." [Addie])

Administration: "For the topical treatment of oral inflammation and ulcers I have been grinding up a single tablet and mixing with c5ml of honey. This pasty mixture is then syringed directly onto the affected areas at regular intervals throughout the day. It is very well tolerated and as I reported previously seems to work wonders in a very short period of time." [Addie])

Cautions/Comments: Dosage (1/2 tab TID) is based on use for GI disturbance. No listed side effects.

5. Antioxidants

Vitamins A, E, C, D

Rationale: Antioxidants repair cell damage and downregulate some inflammatory responses. "Vitamins A, C and E and zinc improve mucous membrane health and possibly have anti-viral and/or immune stimulant activities" [Addie].

Dosage: [Addie]

Vitamin A: 200-400 i.u./kg/day for less than 6 weeks

Vitamin C: 125mg/cat bid

Vitamin E: 25-75 i.u./cat/bid

Administration: Variable. Liquid and powder forms available. Ester C is an ascorbic acid alternative. Use of high-dose injectable vitamin A/ D combination with success has been reported [up to 500,000 IU/ 75,000 IU monthly]. Unverified attribution of combination to Canadian holistic vet.

Cautions/Comments: Vitamin A is a potentially toxic vitamin. Dose with care. Whether long term use of Vitamin C at high dosage predisposes to oxalate crystal formation in kidneys or bladder is a subject of some disagreement. Addition of a diet high in antioxidants A, D3, and E may have been a crucial component in successful thalidomide and lactoferrin treatment [Addie-Radford].

CoQ 10

Rationale: Coenzyme Q10 (CoQ10) is a fat-soluble antioxidant that can regenerate vitamin E in the antioxidant network. Human studies found deficiency of Coenzyme Q 10 in gingiva of human adults suffering from peridontal disease.

Dosage: Variable. 25-30 mg is common. Topical application may be better.

Admininstration: Must always be taken with a fat source. Many forms include the fat source.

Comments: Well established as safe for veterinary use. One study concluded, "These results suggest that topical application of CoQ10 improves adult periodontitis not only as a sole treatment but also in combination with traditional nonsurgical periodontal therapy" [Hanioka].

Niacinamide

Rationale: A form of Vitamin B3 with unique antioxidant properties. Frequently paired with tetracycline derivatives in treatment of pemphigus and other autoimmune inflammatory and eruptive disorders.

Dosage: 150 mg bid; 100 mg tid [unverified dosage]

Administration: Tablet or liquid

Cautions/Comments: Toxic threshold is high. Positive responses to doxycycline-niacinamide combination reported.

6. Hormones

Megestrol Acetate

Rationale: A synthetic female hormone (progestin) with direct and indirect anti-inflammatory properties, commonly used in people to treat cancers and HIV infection (for appetite and weight problems) and in cats to regulate female estrus cycle and to control problem elimination behavior. Also used to treat eosinophilic granuloma complex (EGC). Exercises anti-inflammatory action in a way mimicking that of the glucocorticoids.

Dosage: 1 mg/kg [Bellows]; 2.5-5 mg/cat [Mihaljevic]; 2.5 mg daily for one week, then then once weekly, or 5mg for 3 days, then 1.25mg twice weekly [Dentalvets]. A reported Commonly used scheme is starting with high dose and then reducing: first week: 5mg/day; 2nd week: 5mg/every other day; 3rd week: 5mg/third day and so on.

Administration: Available as 2.5 and 5 mg tablet. Every 3-5 days. Limited term with severe stomatitis, possibly longer term with severe stomatitis plus moderate to severe oropharyngitis [Mihaljevic]

Cautions/Comments: According to one dental vet (staff of the university veterinary med school, Giessen) megestrol acetate has the advantage that it is only immunosuppressive in the mouth. Some vets avoid prolonged use of megestrol acetate (as for estrus regulation or behavioral control) because of possible serious side effects, including behavioral changes, mammary tumors, hyperglycemia, and, uncommonly, liver damage. Contraindicated with various diseases, including kidney disease and diabetes and with various medications, including phenobarbitol. In humans, megestrol acetate has been reported as causing side effects similar to those of steroids: diabetes, adrenal insufficiency, etc. Diabetes has been confirmed in cats. Lethargy and obesity also possible effects. Stimulates appetite. Because of possible side effects, one source “strongly recommended not to use this drug for treating cats” [Didier Carlotti, Clinical Management of the Pruritic Cat], though this was not for stomatitis. Mihaljevic's work found megestrol an effective substitute for steroids when used in combination with feline omega interferon.

7. Immunosuppressants

Thalidomide

Rationale: The precise mode of action is unknown, but thalidomide has uniquely immunosuppressive qualities. Unlike broadly suppressive glucocorticoids, thalidomide selectively suppresses only certain cytokines (notably IL-6 and TNF-α) involved in inflammatory response [Rowland].

Dosage: 50 mg/cat sid-bid

Administration: When sid, give in the evening to account for natural sedative effect.

Cautions/Comments: Widely used as an anti-inflammatory and anticachetic in HIV cases. Use in cats for stomatitis is limited and anecdotal, largely by Dr. Malik in Australia, who reports considerable success. No reports of significant side effects. In humans, an irreversible peripheral neuropathy has been the most notable side-effect. A one-cat study of thalidomide used in conjunction with lactoferrin produced a clinical "cure" of stomatitis and cessation of shedding of calici virus [Addie-Radford]. Difficult to access outside Australia because of its history with regard to causing birth defects.

Sodium Aurothiomalate; Aurothioglucose, Auranofin

Rationale: Used in the treatment of autoimmune diseases such as rheumatoid arthritis and pemphigus. "Gold compounds stabilise lysosomal enzymes, inhibit neutrophil and macrophage migration and phagocytosis, inhibit prostaglandin production and suppress immunoglobulin synthesis. Possibly of more importance, gold salts inhibit helper T-cell responses without affecting the suppressor T-cell population" [Rochette].

Dosage: Aurothioglucose, 1 mg/cat weekly up to 4 months [dentalvet.com/LPGS]; "when initiating gold therapy, the amount given should be increased gradually over several weeks until the appropriate dose is reached" [Rochette]. Auranofin .5-.1 mg/lb bid [Roby].

Administration: Sodium Aurothiomalate, Aurothioglucose, Injection IM. Auranofin, PO, but no mention of its use to treat LPGS.

Cautions/Comments: "Monitor CBC and biochemical profiles weekly initially" [Rochette]. A month or more will be required to see any result. Diarrhea a common side effect of oral form. With gold therapy bone marrow suppression possible, kidney damage rarely. Preliminary testing for sensitivity wise. May be used concurrently with steroids.

Pentoxifylline/Oxypentifylline

Rationale: Several studies showing success in control of recurring human oral ulceration. Several possible modes of action: (1) increase of local blood flow through blood thinning/red cell flexibility; (2) suppression of inflammatory cytokine TNF-alpha protects local nerve sheathing or local tissue inflammation

Dosage: 150 mg sid; 100 mg bid [unverified dosage]. Human dosing suggests bid might be best.

Administration: Available as a 400 mg time-release tablet.

Cautions/Comments: Human studies reported relapse with discontinuation of drug. Possible interaction with cimetidine. Vitamin E may improve drug activity.

Cyclosporin

Rationale: An immunosuppressive drug that revolutionized organ transplant and is now used to treat a variety of autoimmune disorders. Inhibits lymphocyte production and activation. "It mainly blocks T-helper cells but may also suppress T suppressor cells and inhibit release of various lymphokines such as interleuken 2 and T cell growth factor" [Dentalvets]. Various veterinary/dental internet sources suggest its use to treat LPGS [Rochette][Bellows].

Dosage: Starting dose 5 mg/lb orally bid [Roby]; 2 mg/kg bid [Dentalvets]. "Absorption is erratic but Neoral (Novartis) seems to get the best reported absorption. to that end blood levels are checked 4-6 weeks later and adjusted to avoid toxicity and ensure that trough levels are maintained at adequate levels of 250-500ng/m. Over 750-10000 ng/m approaches toxic levels. Once the cat responds the dose can be reduced by lifetime use and monitoring is necessary for most. Labs which perform this test are Antech and Idexx" [Dentalvets]

Administration: Available as capsule and liquid.

Cautions/Comments: Use of a highly immunosuppressive drug in cats with FIV (Chlorambucil has also been suggested) could conceivably be risky. When asked if he would give cyclosporin to an FIV+ cat, one veterinarian replied, " If there is sufficient justification, yes" [Richard Malik BVSc FACVSc PhD, personal communication]. Another, however, replied, "No I would not unless very desperate as it effects T-lymphocytes function. It would be a considered risk benefit analysis considering which immune mediated diseases the cat had vs the clinical impact of the disease vs the potential advantage it may give to FIV" [Jacqueline Norris BVSc, MVS, MASM, PhD, personal communication]. Says an on-line source (not speaking of FIV+ cats), "The combination of immunomodulation with cyclosporine together with laser resection of proliferative tissue should be recommended if extraction of teeth is not desired" [Lyon].

8. Immunomodulators

Feline Omega Interferon, Subcutaneous, Subgingival

Rationale: The primary benefit of recombinant feline omega interferon varies from use to use. In testing it has shown potent antiviral activity against feline calicivirus and feline herpesvirus (see FIV and Upper Respiratory Infection), both (and particularly the first) implicated in feline oral inflammatory disease. Since feline omega is also licensed as an FIV antiviral, it presumably has a favorable effect on whatever synergy FIV infection has added to the oral infection. Interferons generally have an anti-inflammatory immunomodulating activity, and feline omega, being derived from feline cells by recombinant DNA technology, does not provoke an "alien antigen" antibody reponse, as do human interferons given to cats at high dosage by injection.

Dosage: 1 MU/kg SC, 5 x 3 (standard, FIV); 1 MU, 1 x 3 (subgingival); 2.5 MU/kg SC, 1 x 3 (acute calicivirus)

Administration: The standard protocol for administration of Virbagen Omega, Virbac's feline interferon product, is three series of five subcutaneous injections, beginning on day 0, day 14, and day 60. (See Bud’s Medications and Supplements.) In studies of use for treatment of oral disease alone, protocols have varied. Addie recommends the following protocol: "Once every other day for 5 treatments. Thereafter attempt to reduce dosage to twice a week, provided the cat is still doing well. Discontinue treatment only after three attempts to isolate calicivirus have been negative." She adds, "Individual cats require differing regimes of Virbagen Omega injections - some every other day, others only once a week, others recover completely and no longer require injections." Another case history reports use of the same injection protocol, but following the fifth injection, 10,000 IU daily was administered orally in 2 ml of saline for two months, followed by every other day in the third month [Southerden]. Injection directly into the oral cavity (1 MU) has produced dramatic improvement with a single injection [Camy][Mihaljavic], though more may be required. The cat must be briefly anaesthetized, however, to perform this procedure. The most recent update of the treatment protocol for stomatitis by Virbac specifies 3 submucosal injections at 15 day intervals.

Cautions/Comments: No serious side-effects have been recorded. Feline omega interferon is expensive and is not available in the U.S. or Canada; it must be imported from Abbey Vet in Great Britain with a minimum order of one box of five 10 MU vials. Although it has been used in conjunction with steroids in treatment of FIP, the manufacturer advises against concurrent use of steroids. Concurrent use of NSAIDs is not restricted. Many have used FOI with great success, and studies have confirmed a very high rate of success in treating significant feline LPGS. [An invaluable resource for researching studies and field reports of Feline Omega Interferon and other interferons is http://www.vetcontact.com/interferon/index.htm. Enter the type of interferon and the disease to be treated in the search boxes.]

Oral Dilute Interferon: Recombinant Feline Omega, Recombinant Human Alpha, Natural Human Alpha

Rationale: Oral dilute interferon has no direct antiviral action. The theory behind its use is that priming of interferon receptors with small amounts of interferon produce an immune signaling cascade that increases activity in the specific and nonspecific immune systems. The mechanism is unknown.

Dosage: The standard daily dosage of dilute recombinant human interferon alpha for oral administration is 30 IU/Cat; people who have diluted feline omega interferon for similar use seem to use the same dosage, although the manufacturer (Virbac) does not support this use of their product. Dosage recommendations vary, however, from 10 to 30 IU. Dosage recommendations for multi-subtype natural interferon alpha have been set lower (0.5 to 2.0 IU/Cat) [Weiss], but an Italian study (which focused on FIV+ cats, some of which suffered from oral inflammatory disease) used a standard 50 IU dosage [Pedretti]. A 2005 review paper stresses that the doses of 1-5 IU/kg are optimal (there is no discrimination between recombinant and natural interferon), 10 IU/kg being the maximum [Cummins].

Administration: Sources differ on the site of optimal oral distribution via oral syringe. The oral cavity is rich in interferon receptors and the gums, tongue, and other oral tissue are probably all acceptable sites. Care should be taken not to shoot the liquid directly down the throat, nor should it be added to food.

Cautions/Comments: There are no studies of oral interferon as a treatment exclusively of oral disease, although studies of FeLV and FIV have reported improvement of this symptom by clinical scoring and veterinarians frequently prescribe it in the hope that it will help. It has also been prescribed for treatment of herpesvirus, which may play a role in some oral disease. Experience with natural interferon alpha is ongoing. Whether there is any advantage to use of one kind of product over others is not a settled issue.

Cimetidine [Tagamet]

Rationale: Cimetidine HCl is an anti-ulcer drug of the histamine receptor-2 (H-2) blocker class. It is ordinarily used to treat certain GI and cancer problems in cats and dogs. Cimetidine also has immune-modulating activity, however. The presumed rationale for their recommendation for LPGS treatment stems from research that finds an abnormally high number of suppressor T cells in stomatic lesions relative to helper T cells. Histamine activates these suppressor T cells. Cimetidine inhibits this suppressor T cell activity and so helps to normalize immune response. Addie adds, "Cimetidine is being recognised to stimulate the Th1 response" through upregulation of interferon-gamma and interleuken-2.

Dosage: No dosage is suggested for stomatitis, but 5-10 mg every 6-8 hours is a common feline dosage for other purposes.

Administration: Available as liquid or tablet

Cautions/Comments: Several sources [Cebuliak, Addie] recommend trying cimetidine as a safe alternative to raising steroid dosages, but there is no internet record discoverable on actual experience or results with feline stomatitis. Interest has evidently been sparked by reports of its use in successful treatment of human PFAPF (Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome), a human childhood disorder. Does have some drug interactions (e.g., diazepam).

9. Immunopotentiators

Levamisole Hydrochloride/Phosphate

Rationale: Levamisole seems to regulate cell mediated immune reactions by restoring effector functions of peripheral T-lymphocytes and phagocytes and by stimulating precursor T-lymphocytes to differentiate into mature cells. It has shown success since the 1970s in treatment of human inflammatory autoimmune diseases, including recurring apthous stomatitis. There are no studies of levamisole as therapy for feline LPGS.

Dosage: 25 mg p o every other day for 3 treatments [Rochette] [unclear whether dosage regimen is repeated at intervals]

Administration: Available as a powder and injectable liquid. Used at high dosage for worming.

Cautions/Comments: The immunopotentiating effect is highly dose dependent. Doses too large or given for too long a time are immunosuppressive. A study in rats found 2-4 mg/kg to be an optimal dosage.

Bovine Lactoferrin

Rationale: Ample experimental and clinical precedent. Proven effective in about 20% of cases. Native lactoferrin is found in reduced quantities in LPGS tissue as compared to normal oral tissue. Various potential modes of action: (1) neutrophil potentiation to scavenge oral bacteria; (2) inhibitory action against feline herpesvirus [Maggs], feline calicivirus [McCann], and feline immunodeficiency virus; (3) TH1 cytokine profile

Dosage: 40 mg/kg [Bellows] or more

Administration Apply as powder to oral tissue or mix with liquid (e.g., milk) and apply as a slurry. Admin with food said to be less desirable.

Cautions/Comments: Bovine lactoferrin has no known overdose or toxicity. Should not be given at the same time as iron-containing products. Lactoferrin binds iron.

10. Analgesics

Amantadine

Rationale: An antiviral drug used to treat Parkinson's disease. Has "NMDA [N-methyl D-aspartate nerve] receptor blocking activity" and "is used in conjunction with [a] primary analgesic to prevent dorsal horn [of the spine] windup [activation]" [Headley] NMDA receptors appear to be pivotal in the induction and maintenance of some chronic and pathological pain states,in part due to sensitization of sensory neurons in the dorsal horn of the spine.

Dosage: 3-5mg/kg daily [Thompson]

Administration: Available in syrup (10 mg/ml) or (human) 100 mg tablet [Thompson]. One source uses in 7-10 increments; another cites 21 day use. "It may be given on a continual basis if needed, though in most cases it can be given daily for 7-14 days and then discontinued until pain worsens again" [Thompson]

Cautions/Comments: "It has no significant analgesic effect of its own, so must be considered a supplement for those animals that opoids and/or NSAIDs are not quite doing the job [for]" [Headley]. "Not only reduces sensitization (always helpful in chronic pain) but also seems to enhance opoid receptor sensitivity and help abolish opoid tolerance. I use it . . . when opoid effectiveness seems to be waning, and subjectively feel it helps quite a bit" [Old]. Side effects minimal. Occasional agitation or diarrhea.

Tramadol

Rationale: Nonaddictive analgesic, nonsedative opiate, a synthetic analogue of codeine with a low affinity for opioid receptors.

Dosage: 2-4mg bid-tid [VIN]. Report of time release formulation created by compounding with "hydroxypropylmethycellulose as the diluent" that works optimally bid.

Administration: With or without food

Cautions/Comments: May be given concurrently with NSAIDS. Avoid forms intended for humans that also contain acetaminophen. "The degree of mu agonism produced is relatively weak (the parent compound has very little affinity for the mu receptors; most of the mu effects come from the M1 metabolite). However, in conjunction with the monoamine reuptake inhibition a powerful synergistic action occurs, leading to analgesia comparable to meperidine or codeine. It is helpful in a variety of acute and chronic pain syndromes, including neuropathic pain and allodynia. Combining tramadol with other analgesics (NSAID’s, mu agonists) further enhances tramadol’s efficacy, producing a multimodal pain relieving action. . . . Side effects, though rare, may include GI upset and sedation." [Robertson]. This is a bitter medication and it is not always easy administered to cats via the oral route.

Butorphanol [Torbutrol, Torbugesic]

Rationale: "A mu-opioid antagonist that produces its analgesic actions through kappa agonist activity. It rapidly reaches a ceiling effect, is short acting" [Robertson et al].

There are 4 types of opioid receptors, with multiple receptor subtypes. Mu receptors produce the most profound analgesia. Kappa receptors trigger a lesser analgesic response [Thompson].

Dosage: [Oral] 0.2-0.8 mg/kg q 6-8hrs; Injectable butorphanol (10 mg/ml) can be mixed 1 ml in 30 ml of a palatable liquid feline vitamin supplement and dosed orally at 1 ml–3 ml q 6–8 h [Klein]; 0.1-0.4 mg/kg [Robertson et al]; [SubQ] .2 mg/kg tid [Roby]

Administration: Liquid or tablet for sustained use; injection for post-op/immediate pain control

Cautions/Comments: "A weaker analgesic than pure mu opioids" [Robertson et al]. "Mixed agonist/antagonists like butorphanol (CIV) are not considered useful in the management of chronic pain. First-pass effect destroys some of the drug, and the analgesia is considered to be relatively short-lived (1-2 hours)"[Thompson].

Buprenorphine

Rationale: "A partial mu-agonist, is the most popular opioid [for pain relief] used in small animal practice in the UK, other parts of Europe, Australia and South Africa" [Robertson]. Better and longer duration of analgesia than morphine. Opioids can act as agonists (bind and stimulate receptors), antagonists (bind and block or inhibit activity), partial agonists (bind and stimulate, but with less than full activity at certain receptor subtypes), and mixed agonist/antagonists (stimulating some receptors while blocking others). Partial mu agonists bind at the mu receptors but only partially activate them.

Dosage: 0.01-0.02 mg/kg [Roby]; .03 mg/kg provides 8-10 hrs analgesia [Thompson].

Administration: IM or SubQ; PO 1 mg divided bid [PO source unverified]. "Buprenorphine is not available as an oral preparation (significant first-pass effect renders it inactive), but its lipophilic nature lends itself to absorption across skin or mucous membranes. Compounding pharmacies can produce a PLO (pleuronic lecithin organogel, or transdermal gel) for application on the inner surface of the pinna or shaved skin on the neck in dogs and cats. Alternatively, the alkaline salivary pH of cats allows for excellent transmucosal absorption when the injectable drug is given in the mouth (it should not be mixed with flavored syrups, as swallowing will inactivate it; the injectable form is tasteless and well-tolerated by cats)' [Thompson].

Cautions/Comments: "In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats" [Robertson et al]. Outperformed ketoprofen IM in a trial of post-operative analgesics [Dobbins]. "Buprenorphine (CIII) is the prototypical drug in this class; it’s moderately expensive but VERY safe, producing few side effects and minimal sedation . . . . A ceiling effect on analgesia exists with partial agonists, making them less useful for severe pain" [Thompson].

Fentanyl Patches

Rationale: The active ingredient, fentanyl citrate, is approximately 75 times more potent than morphine, yet produces fewer histaminic side effects. "Fentanyl patches are becoming an important part of pain management for the cat. This is because fentanyl provides quality pain control with few adverse effects. In addition, the transdermal system bypasses the need to orally medicate the cat" [Ogilvie]. "During a particularly painful flare up sometimes . . . helpful for pain control" [Brooks]

Dosage: Patches are available in strengths of 25, 50, 75, and 100 mcg per hour. Because of the cat's small size, only the 25 mcg per hour size is recommended.

Administration: Change every 3-5 days. Apply small plastic patch to the back of a foot.

Cautions/Comments: ". . . benefits include portability, infrequent dosing, manageable side effects, non-oral administration, and efficacy comparable to morphine. Negatives include cost, the possibility of typical opioid adverse effects, and slow peak time. Its ease of use and client and patient satisfaction should encourage all practitioners dealing with severe chronic and some acute pain to familiarize themselves with its use" [Ogilvie].

Sucralfate [Carafate]

Rationale: Feline indications are for esophageal or gastric ulceration, but used off-label for oral ulcers and much research in humans for aphthous ulcers and oral mucositis. Binds to and forms a protective coating on ulcerated sites. Also, "Sucralfate binds epidermal growth factor, thus causing it to accumulate in ulcerated lesions . . . Sucralfate also increases mucosal blood flow either by inducing local noitric oxide or prostaglandin production . . . or by directly stimulating mucosal angiogenesis [i.e., blood vessel formation]" [Boothe].

Dosage: Depends on extent of problem (tongue? throat? esophagus?). 250 mg per dose [Roby]

Administration: Mix with water to make a slurry; admin 2-4 times daily PO

Cautions/Comments: Regarded as a very safe drug for cats, but has many drug interactions [e.g., cimetidine]. "One thing I would point out regarding Sucralfate; it comes bound to aluminium and requires an acid medium before it is activated (BSAVA Formulary 3rd Edition). Given feline saliva is alkaline (http://www.vasg.org/opioid_analgesics.htm) it should not theoretically work anywhere other than the stomach (and possibly small intestine if bicarb production is insufficient). That said, I believe that the pH of human saliva is also over 7, so if it works for them maybe it works for cats too" [Jon Bray BVSc MRCVS, personal communication].

Chamomile

Rationale: The following is concluded from a 2006 Brazillian study of "fluid extract from Chamomilla recutita" in humans with oral inflammatory disease: "The analgesic effect was considered excellent by 82% and good by 18% of the patients, as demonstrated with the Analogical Visual Scale for chronic and experimental pains after 5, 10, and 15 minutes. Tolerance was evaluated as excellent by 97% and good by 1% of the subjects. The fluid extract from Chamomilla recutita, due to its analgesic effect, may give these patients a better quality of life" [Ramos-e-Silva].

Dosage: No information

Administration: "Most animals" are said to like the taste, and it is soluble in water and available in glycerine tinctures.

Cautions/Comments: Chamomile interactions with aspirin and with central nervous system depressive drugs have been recorded. One pet herbal source characterizes chamomile as "one of the safest herbs in existence," although individual allergic reactions are always within the realm of possibility.

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