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Lactated Ringer’s Solution


Trade and Other Names: LRS


Functional Classification: Fluid replacement



Pharmacology and Mechanism of Action


Lactated Ringer’s solution is a fluid solution for replacement intended for intravenous administration. Lactated Ringer’s solution contains a balanced combination of electrolytes and an alkalinizing buffer. This solution contains 28 mEq/L of lactate.



Indications and Clinical Uses


Lactated Ringer’s solution is indicated as a replacement or maintenance fluid. It also is used as a vehicle to deliver intravenous medications via constant rate infusion (CRI). It has been administered SQ, intraosseous (in bone medullary cavity), and intraperitoneal (IP) in animals when intravenous access is not possible. It contains lactate, a metabolizable base, but will not correct acidosis as quickly as bicarbonate. Severely acidemic animals may already have high lactate serum levels.



Precautionary Information



Adverse Reactions and Side Effects


No significant adverse effects.



Contraindications and Precautions


Administer intravenous fluids only in patients monitored carefully.



Drug Interactions


Lactated Ringer’s solution has a pH of 6-7.5. Do not add medications to this solution if they are unstable at this pH. Lactated Ringer’s contains calcium. Do not add drugs to this solution that may bind (chelate) to calcium.



Instructions for Use


Fluid requirements vary depending on animal’s needs (replacement vs. maintenance). For shock therapy, administer one-half the calculated dose in the first 30 minutes and in 10-mL/kg increments every 15 minutes, followed by a CRI. For severe acidemia, consider fluids supplemented with bicarbonate instead of lactate.



Patient Monitoring and Laboratory Tests


Monitor patient’s hydration status and electrolyte balance. With high administration rates, monitor patient for signs of pulmonary edema.



Formulations


Lactated Ringer’s solution is available in 250-, 500-, and 1000-mL fluid bags.



Stability and Storage


Store in a tightly sealed container. If container has been punctured or transferred to another container, sterility cannot be assured.



Small Animal Dosage



Dogs and Cats



• Moderate dehydration: 15-30 mL/kg/hr IV.

• Severe dehydration: 50 mL/kg/hr IV

• Maintenance: 55-65 mL/kg/day IV, SQ, or IP (2.5 mL/kg/hr).

• During anesthesia: 10-15 mL/kg/hr IV.

• Shock therapy: (for dogs) 90 mL/kg IV and (for cats) 60-70 mL/kg IV.


Large Animal Dosage



Cattle, Horses, and Pigs



• Maintenance: 40-50 mL/kg/day IV.

• Moderate dehydration: 15-30 mL/kg/hr IV.

• Severe dehydration: 50 mL/kg/hr IV.


Calves and Foals



• Moderate dehydration: 45 mL/kg at a rate of 30-40 mL/kg/hr IV.

• Severe dehydration: 80-90 mL/kg at a rate of 30-40 mL/kg/hr IV. In severe cases it may be given as rapidly as 80 mL/kg/hr.


Regulatory Information


There is no risk of harmful residues in animals intended for food. No withdrawal times are necessary.



Lactulose



lak′tyoo-lose


Trade and Other Names: Chronulac and generic brands


Functional Classification: Laxative



Pharmacology and Mechanism of Action


Laxative. Lactulose is a disaccharide sugar containing one molecule of fructose and one molecule of galactose. Lactulose produces a laxative effect by osmotic effect in the colon. It is a nonabsorbed sugar and retains water in the intestine after oral administration via an osmotic effect. Lactulose also will decrease the pH of the intestinal lumen.



Indications and Clinical Uses


Lactulose is administered orally for treatment of hyperammonemia (hepatic encephalopathy) because it decreases blood ammonia concentrations via lowering the pH of the colon; thus ammonia in the colon is not as readily absorbed. Lactulose also is administered orally to produce a laxative effect for treatment of constipation.



Precautionary Information



Adverse Reactions and Side Effects


Excessive use may cause fluid and electrolyte loss.



Contraindications and Precautions


Use lactulose with caution in animals with diabetes because it contains lactose and galactose.



Drug Interactions


No drug interactions are reported for animals.



Instructions for Use


In veterinary medicine, clinical studies to establish efficacy are not available. In addition to doses cited, 20-30 mL/kg of 30% solution retention enema has been used in cats.



Patient Monitoring and Laboratory Tests


When used for treating hepatic encephalopathy, monitor the patient’s hepatic status.



Formulations


Lactulose is available in 10 g/15 mL liquid solution (3.3 g per 5 mL).



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature. It is soluble in water. Darkening of the solution may occur without affecting stability. Avoid freezing.



Small Animal Dosage



Dogs



• Constipation: 1 mL/4.5 kg q8h (to effect) PO.

• Hepatic encephalopathy: 0.5 mL/kg q8h PO.


Cats



• Constipation: 1 mL/4.5 kg q8h (to effect) PO.

• Hepatic encephalopathy: 2.5-5 mL/cat q8h PO.


Large Animal Dosage



Horses and Cattle



• 0.25-0.5 mL/kg/day PO.


Regulatory Information


There is little risk of residues in animals intended for food. No withdrawal times are necessary.



Leflunomide



le-FLOO-noe-mide, or leh-FLEW-nah-mide


Trade and Other Names: Arava and generic


Functional Classification: Immunosuppressive drug



Pharmacology and Mechanism of Action


Leflunomide is an isoxazole immunosuppressive drug. Leflunomide is not active as the parent drug, but it is converted to an active metabolite A77 1726 (also known as M1 and Teriflunomide), which inhibits T-cell and B-cell proliferation and is responsible for clinical immunosuppressive effects. It inhibits the synthesis of pyrimidine via inhibition of the enzyme dihydroorotate dehydrogenase. This enzyme is important for the de novo pyrimidine synthesis, which is critical for function of activated and stimulated lymphocytes. It also may produce anti-inflammatory effects by inhibiting proinflammatory cytokines.


After oral absorption, the plasma levels of leflunomide are low or undetectable. Therapeutic effects are produced from the metabolite A77 1726 (M1) for the immunosuppressive action. If monitoring is performed, the measurement should focus on the metabolite concentrations. In people, the metabolite M1 has a very long half-life of approximately 2 weeks. But, in limited studies in dogs, the half-life was only 21 hours, and the peak concentrations were much lower than in people. In people the long half-life requires several days to accumulate to steady-state levels and to decline from a peak level. Loading doses are often administered in people. However, because of the shorter half-life, loading doses are not needed in dogs and steady-state concentrations will be attained in approximately 5 days.



Indications and Clinical Uses


This drug is used in people primarily for rheumatoid arthritis. In dogs it has been used for a variety of immune-mediated diseases as a substitute for other drugs such as azathioprine or mycophenolate. These diseases include myasthenia gravis, Evan’s syndrome, immune-mediated hemolytic anemia and thrombocytopenia, and polymyositis/polyarthritis. Efficacy has not been studied in controlled clinical studies but are reported anecdotal observations.



Precautionary Information



Adverse Reactions and Side Effects


The most common adverse effects in dogs have been decreased appetite and diarrhea. Mild anemia and lethargy also have been observed. Although rare, leukopenia is possible and periodic CBC to monitor patients is recommended.



Contraindications and Precautions


Do not administer to pregnant animals. This drug can be toxic to a developing fetus.



Drug Interactions


No interactions are reported.



Instructions for Use


Leflunomide is used most often in dogs for immunosuppressive treatment when other drugs have failed or when the patient has become refractory to other drugs and a substitute is considered. The dosing protocols used currently are derived from extrapolation and some anecdotal reports. Most veterinarians start with 4 mg/kg per day, then lower the dose as the patient responds. Pharmacokinetic studies in dogs suggest that the dose of 4 mg/kg per day may not produce drug levels that are considred therapeutic. Therefore, in patients that have not responded, there should be consideration for higher doses.



Patient Monitoring and Laboratory Tests


Monitor CBC and platelet counts in treated animals. Anemia has been reported as a consequence of treatment. If blood monitoring is pursued, plasma samples may be collected and measured for A77 1726 (the active metabolite). This metabolite is stable in serum for up to 5 months under refrigerated conditions. Drug concentrations at 12 hours (trough) are considered effective if greater than 20 mcg/mL.



Formulations


Available in 5-, 10-, and 20-mg tablets.



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature.



Small Animal Dosage



Dogs



• 4 mg/kg per day, usually in divided doses of 2 mg/kg q12h, tapered to 2 mg/kg q24h, PO. After an induction period, the dose may be decreased by 25% increments until the patient is stabilized or until the disease resolves. Some patients may require higher starting doses.


Cats



• No dose has been reported for cats.


Large Animal Dosage


No large animal doses are available.



Regulatory Information


Withdrawal times are not established for animals that produce food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).



Leucovorin Calcium



loo-koe-vor′in kal′see-um


Trade and Other Names: Wellcovorin and generic brands


Functional Classification: Antidote



Pharmacology and Mechanism of Action


Leucovorin is a reduced form of folic acid that is converted to active folic acid derivatives for purine and thymidine synthesis.



Indications and Clinical Uses


Use of leucovorin is uncommon in animals. It may be used as an antidote for folic acid antagonists. In humans it is primarily used as rescue for overdoses of folic acid antagonists (methotrexate) and treatment of adverse reactions from methotrexate but also may be considered for reactions caused by pyrimethamine and trimethoprim.



Precautionary Information



Adverse Reactions and Side Effects


No adverse reactions reported for animals, but allergic reactions have been reported in people.



Contraindications and Precautions


No contraindications reported for animals.



Drug Interactions


Leucovorin will interfere with action of trimethoprim and pyrimethamine.



Instructions for Use


Clinical studies have not been reported in veterinary medicine. Although leucovorin may prevent toxicity from trimethoprim, it will not prevent toxic reactions that may be caused by sulfonamides in animals.



Patient Monitoring and Laboratory Tests


Monitor CBC if this drug is used to treat overdose of folic acid antagonists.



Formulations Available


Leucovorin is available in 5-, 10-, 15-, and 25-mg tablets and 3- and 5-mg/mL injection.



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature. It is soluble in water but is insoluble in ethanol. Reconstituted solutions have stability for 7 days at room temperature or refrigerated.



Small Animal Dosage



Dogs and Cats



• With methotrexate administration: 3 mg/m2 IV, IM, or PO.

• As antidote for pyrimethamine toxicosis: 1 mg/kg q24h PO.


Large Animal Dosage


No large animal doses are reported. However, if pyrimethamine toxicosis is suspected in horses, doses listed for small animals may be considered.



Regulatory Information


Withdrawal times are not established for animals that produce food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).



Levamisole Hydrochloride



leh-vam′ih-sole hye-droe-klor′ide


Trade and Other Names: Levasole, Ripercol, Tramisol, and Ergamisol


Functional Classification: Antiparasitic



Pharmacology and Mechanism of Action


Levamisole is an antiparasitic drug of the imidazothiazole class. It eliminates a variety of parasites via neuromuscular toxicity. Levamisole has an immunorestorative effect in animals, but the mechanism of action on the immune system is unknown. It may activate and stimulate proliferation of T-cells; augment monocyte activation; and stimulate macrophages, including phagocytosis and chemotaxis. It may increase neutrophil mobility. However, it is not cytotoxic to neutrophils or immune cells.



Indications and Clinical Uses


In cattle and sheep, it is used to treat a variety of nematodes, including stomach worms (Haemonchus, Trichostrongylus, and Ostertagia species), intestinal worms (Trichostrongylus, Cooperia, Nematodirus, Bunostomum, Oesophagostomum, and Chabertia species), and lungworms (Dictyocaulus species). In pigs it is used to treat nematodes such as large roundworms (Ascaris suum), nodular worms (Oesophagostomum species), intestinal thread worms (Strongyloides ransomi), and lungworms (Metastrongylus species). Levamisole has been used for treatment of endoparasites in dogs and as a microfilaricide. Macrocyclic lactones (e.g., milbemycin oxime or ivermectin) are considered a preferred heartworm microfiliaricide. In people, levamisole is used as an immunostimulant to aid in treatment of colorectal carcinoma and malignant melanoma. In animals, levamisole also is used as an immunostimulant, but reports of efficacy are lacking.



Precautionary Information



Adverse Reactions and Side Effects


Levamisole may produce cholinergic toxicity. It has produced vomiting in some dogs. The injectable formulation has caused some swelling at the site of injection. In humans, when used as an immunostimulant, it has caused stomatitis, agranulocytosis, and thrombocytopenia.



Contraindications and Precautions


Use cautiously in animals with high heartworm microfilaria burdens. Reactions are possible from heavy kill rate of microfilaria. There are no adverse reactions on fertility and no effects on pregnancy. In rats and rabbits there was no evidence of teratogenicity or embryotoxicity at doses of 180 mg/kg. Levamisole is abused in people and often mixed with cocaine to either potentiate the effects to produce additional CNS stimulation, or is added as a marker compound. When used in this form in people, it has produced agranulocytosis in some individuals. Levamisole may potentially be converted to Aminorex, a CNS stimulants in horses, with amphetamine properties, which may affect performance.



Drug Interactions


Do not use with pyrantel because they share the same mechanism of toxicity.



Instructions for Use


In heartworm-positive dogs, it may sterilize female adult heartworms. Levamisole has also been used as an immunostimulant; however, clinical reports of its efficacy are not available. Because of the possibility of contamination at the injection site, use a clean needle with each animal and clean the injection site.



Patient Monitoring and Laboratory Tests


Monitor for microfilaria before treatment because of risk of reaction with a high heartworm burden.



Formulations


Levamisole is available in 0.184-g bolus; 2.19-g bolus; 9-, 11.7-, and 18.15-g per packet; 136.5-mg/mL and 182-mg/mL injection (levamisole phosphate); and 50-mg tablet (Ergamisol).



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated.



Small Animal Dosage



Dogs



• Endoparasites: 5-8 mg/kg once PO (up to 10 mg/kg PO for 2 days).

• Hookworms: 10 mg/kg/day for 2 days.

• Microfilaricide: 10 mg/kg q24h PO for 6-10 days (recommended to use macrocyclic lactones instead).

• Immunostimulant: 0.5-2 mg/kg 3 times/week PO. (In humans the immunostimulant dose is given q8h for 3 days.)


Cats



• Endoparasites: 4.4 mg/kg once PO.

• Lungworms: 20-40 mg/kg q48h for 5 treatments PO.


Large Animal Dosage



Cattle and Sheep



• 8 mg/kg once PO, or approximately one 2.19 g bolus per 450-750 pounds (200-340 kg).

• Levamisole injection (for cattle): 8 mg/kg SQ into mid neck area, once, or approximately 2 mL per 100 pounds (45 kg).


Pigs



• 8 mg/kg in drinking water.


Regulatory Information


Cattle withdrawal time (meat): 2 days (PO) and 7 days (SQ injection).


Sheep withdrawal time (meat): 3 days.


Pig withdrawal time (meat): 3 days.


Horses: There are some reports that levamisole can be converted to Aminorex in horses, which is a CNS stimulant and a banned substance in racing horses.



Levetiracetam



lev-eh-teer-ass′eh-tam


Trade and Other Names: Keppra


Functional Classification: Anticonvulsant



Pharmacology and Mechanism of Action


Anticonvulsant. The mechanism of action is not certain, but it does not involve inhibitory neurotransmitters. It inhibits burst firing of neurons without affecting normal neuronal excitement. It does not undergo hepatic metabolism but may undergo metabolism that does not include cytochrome P450 enzymes. Elimination relies on renal clearance.



Indications and Clinical Uses


In dogs, levetiracetam has been used to treat seizures, especially those refractory to other anticonvulsants. In dogs, it has been considered a drug of choice as an add-on medication when patients are refractory to phenobarbital and bromide therapy. It often is used in combination with other anticonvulsants. Levetiracetam has been used to treat seizure disorders in cats at a dose of 20 mg/kg every 8 hours and found to be effective in some cases. In dogs the oral absorption is 100%, the half-life is 3-4 hours, and the volume of distribution is 0.4-0.5 L/kg. In cats the oral absorption is also 100%, with a half-life of 3 hours and a volume of distribution similar to dogs.



Precautionary Information



Adverse Reactions and Side Effects


Weakness, lethargy, and dizziness have been reported in people. Adverse effects have been rare in animals, except for occasional lethargy and decreased appetite.



Contraindications and Precautions


No known contraindications.



Drug Interactions


Ordinarily, there are no direct interactions with drugs that inhibit or induce cytochrome P450 enzymes. However, studies in dogs and people have confirmed that phenobarbital can enhance the clearance of levetiracetam. For example, the half-life is shorter and clearance is more rapid when dogs are administered phenobarbital simultaneously. The mechanism for the interaction is unknown. Interactions with other concurrently used anticonvulsants have not been reported.



Instructions for Use


It is rapidly and completely absorbed, and absorption is not affected by feeding. An injectable formulation is available but not used often in veterinary medicine. However the injectable solution has been administered at a dose of 20 mg/kg IV bolus increments to a maximum of 60 mg/kg in emergency situations.



Patient Monitoring and Laboratory Tests


Monitor seizure frequency. Currently no clinical monitoring test for serum exists in routine laboratories. However, some laboratories have this capability. Therapeutic plasma/serum concentrations in people are in the range of 5-45 mcg/mL.



Formulations


Levetiracetam is available in 250-, 500-, and 750-mg tablets.



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated. It is soluble in water, and it may be acceptable to mix with other foods, syrups, or flavorings immediately prior to oral administration.



Small Animal Dosage



Dogs



• 20 mg/kg q8h, PO. More frequent administration or higher doses may be necessary with concurrent phenobarbital treatment.

• Intravenous use (emergency situations): 20 mg/kg IV bolus, repeated if necessary up to 60 mg/kg.


Cats



• 20-mg/kg q8h PO.


Large Animal Dosage


No dose has been reported for large animals.



Regulatory Information


No regulatory information is available. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).



Levodopa



lee′voe-doe′pah


Trade and Other Names: Larodopa and L-dopa


Functional Classification: Dopamine agonist



Pharmacology and Mechanism of Action


Dopamine, when administered systemically, does not cross the blood–brain barrier. However, levodopa crosses more easily via a carrier-mediated process and is converted to dopamine after crossing the blood–brain barrier. Dopamine is used in neurodegenerative disorders to stimulate CNS dopamine receptors.



Indications and Clinical Uses


In people, levodopa is used for treating Parkinson’s disease, and it is used in combination with carbidopa (a peripheral decarboxylase inhibitor) and entacapone (an o-methyltransferase inhibitor) to potentiate therapy. In animals, it has been used for treating hepatic encephalopathy.



Precautionary Information



Adverse Reactions and Side Effects


Adverse effects in animals have not been reported. In people, dizziness, mental changes, difficult urination, and hypotension are among the reported adverse effects.



Contraindications and Precautions


There are no specific contraindications for use in animals.



Drug Interactions


Antidopamine drugs will interfere with action. Such drugs include metoclopramide, phenothiazines (e.g., acepromazine), and risperidone.



Instructions for Use


Clinical studies have not been reported in veterinary medicine. Titrate dose for each patient.



Patient Monitoring and Laboratory Tests


No specific monitoring is necessary.



Formulations Available


Levodopa is available in 100-, 250-, and 500-mg tablets or capsules.



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature. Levodopa is slightly soluble in water but more soluble in acid solutions. It will be rapidly oxidized with exposure to air, which will be indicated by a darkening of the formulation. Injectable solutions have been prepared extemporaneously and found to be stable for 96 hours.



Small Animal Dosage



Dogs and Cats



• Hepatic encephalopathy: 6.8 mg/kg initially, PO, then 1.4 mg/kg q6h, PO.
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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on L

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