Veterinarians often have trouble obtaining the human approved drug Lysodren (mitotane or o,p’-DDD). In fact, frustrated pet owners sometimes return to their veterinarian with an unfilled prescription in hand when they are unable to find a pharmacy that stocks this medication. Mitotane is used in an extra-label manner to treat the more severe or complicated cases of pituitarydependent hyperadrenocorticism (PDH) in dogs, also referred to as Cushing’s syndrome, and for treatment of adrenocortical tumors. Although selegiline (Anipryl”) was recently approved for veterinary use in the treatment of PDH, mitotane remains the drug of choice of many veterinarians for the more complicated cases that do not respond to selegiline. Since Lysodren'” may not normally be stocked by most local pharmacies, it is a good idea to let your pharmacist know in advance that you may need this drug. Finding a source for Lysodren” in advance can save the veterinarian and the veterinary client valuable time and also prevents delay in initiation of therapy. Also, small dogs (less than 5 kg in body weight) may pose a particular dosing problem with mitotane.
Pharmacists can assist the veterinarian in reformulating this medication to meet a particular patient’s dosing needs.
When prescribing or dispensing mitotane, instruct clients to:
- administer mitotane with food or corn oil to increase tolerance of the drug and to enhance oral absorption,
- wash their hands after administering mitotane and keep the tablets out of reach of children or pets,
- report to their veterinarian if their dog stops eating, starts vomiting, or shows signs of lethargy, weakness, dry eyes, or diarrhea,
- be familiar with the signs of acute hypoadrenocorticism (also called an addisonian crisis, which is a life-threatening emergency requiring immediate intervention by the veterinarian) such as bradycardia or weak pulse, weakness & depression leading to collapse, dehydration, shaking or shivering. reluctance to walk.
Ketoconazole (Nizoral) is another human-approved drug that is used in the treatment of PDH in dogs. This drug is an antifungal, which also inhibits steroid synthesis and may be better tolerated than mitotane in some dogs. Remember that ketoconazole has some quite significant drug interactions; therefore, look at any concurrent therapy before prescribing Nizoral”‘. If the patient is also getting drugs which increase stomach pH, such as antacids, anticholinergics (such as propantheline, etc.), or H2 antagonists (such as cimetidine, ranitidine, etc), give these drugs two hours after the Nizoral”” dose to achieve maximum absorption of ketoconazole. Cisapride (Propulsid”) is a drug that should not be given concurrently with ketoconazole, according to the manufacturer. Increased plasma concentrations of cisapride with resultant ventricular arrhythmias may result if coadministered with ketoconazole, itraconazole, IV miconazole or troleandomycin. Other possible drug interactions with ketoconazole include theophylline, mitotane, warfarin, phenytoin, methylprednisolone, ethanol, rifampin. cyclosporine. Ketoconazole should also be used cautiously with any other hepatotoxic agents. Ask pharmacists for assistance with drug interaction information.
Although not approved for veterinary use, this humanapproved drug has been used in cats to treat stubborn upper respiratory infections (caused by susceptible organisms) that do not respond to conventional methods. This drug is particularly appealing to cat owners who have difficulty dosing their cats, since it has a favorable dosing schedule. The pharmacokinetics of the drug in cats have been published. Cats have a higher bioavailability than humans, but apparently less than dogs. Especially appealing to cat owners is the infrequent dosing schedule of every 72 hours. Some veterinarians have also used once weekly dosing with apparent success.
The most commonly used dose in cats for upper respiratory infections appears to be 5 mg/kg PO every 72 hours, although the dose range has been reported to be 5 to 10 mg per kilogram every 24 hours, every 48 hours, every 72 hours, and even once weekly with a duration of 4 to 8 weeks of therapy. Other doses used have included one-fourth to one-half tablet for the average cat every 72 hours. The dose, frequency of administration, and the duration of treatment varies depending upon the disease state being treated. The pediatric suspension may be used for accurate dosing of small patients, although some cats may not like the flavor. Anecdotal information exists that the reconstituted pediatric suspension has been kept under refrigeration beyond the labeled expiration date and used for up to 4 weeks in cats, but this practice should not be recommended lacking reliable stability information for this length of time.
There appears to be a nation wide shortage of phenobarbital injection, which has created problems for many veterinarians treating pets with seizure disorders. Phenobarbital injection is used primarily in the clinic during the loading phase, while the oral medication is then sent home with the owner for maintenance therapy. As existing stocks of the injection dwindle, veterinarians may turn to pharmacists for assistance in obtaining this product. There appears to be a sporadic supply of the human approved drug, Luminal’® 130mg/ml ampules. If the commercial product is unavailable, pharmacists can also compound the injection. There appears to currently be no shortage of the chemical form for compounding or of the oral tablets. Remember that phenobarbital is a DEA Class IV controlled substance and must be handled according to state and federal laws.
Keeping Up With New Drugs
Gastric ulcers are a common problem in both young and adult horses, especially those in stressful environments, and may cause debilitation and death (particularly in young foals). FDA’s Center for Veterinary Medicine (CVM) has approved the first drug, GastroGard® (omeprazole), for treatment and prevention of recurrence of gastric ulcers in horses and foals greater than 4 weeks of age. Safety in pregnant or lactating mares has not been determined. GastroGard”‘ is now available (as of April, 1999) as an oral paste in a calibrated syringe and is sold by Merial Limited of Iselin, New Jersey. It is a prescription drug and therefore must be prescribed and/or dispensed within the context of a valid veterinarian/client/patient relationship. The daily cost of the medication to the veterinarian for the average horse will be approximately $32 per day.