Naquasone Bolus

Manufacturer: Schering-Plough

(trichlormethiazide And Dexamethasone)

Veterinary

For Oral Use In Dairy Cattle Only

NADA 30-136, Approved by FDA

Naquasone Bolus Caution

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

Description

NAQUASONE Bolus contains 200 mg trichlormethiazide and 5 mg dexamethasone. It combines the effective diuretic activity of trichlormethiazide with the specific anti-inflammatory activity of dexamethasone. This combination of activities is complementary in the reduction of physiological parturient edema of the mammary gland and associated structures in cattle. Because the two drugs are complementary in action, effects are achieved with minimum dosage of trichlormethiazide.

Warning

Milk taken from dairy animals during treatment and for 72 hours after the latest treatment must not be used for food.

Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis.

Additionally, corticosteroids administered to dogs, rabbits, and rodents during pregnancy have produced cleft palate. Other congenital anomalies including deformed forelegs, phocomelia, and anasarca have been reported in offspring of dogs which received corticosteroids during pregnancy.

Naquasone Bolus Indications

NAQUASONE is recommended for the treatment of physiological parturient udder edema of the mammary gland and associated structures in cattle.

Dosage

One or two boluses initially followed by 1/2 to 1 bolus daily depending on the size and response of the animal and the severity of the edema. Total duration of treatment should not exceed 3 days.

The usual case of edema seen under field conditions will generally begin to respond within 24-48 hours after NAQUASONE therapy is initiated. Most cases will subside in 3 to 4 days. If results are not evident in 3 days, it is recommended the animal be re-examined.

Side Effects

Side effects such as SAP and SGPT enzyme elevations, weight loss, anorexia, polydipsia, and polyuria have occurred following the use of synthetic corticosteroids in dogs. Vomiting and diarrhea (occasionally bloody) have been observed in dogs and cats.

Cushing's syndrome in dogs has been reported in association with prolonged or repeated steroid therapy.

Precautions

For all the beneficial effects of the corticosteroids one should be aware of the possible untoward reactions resulting from their use. Dexamethasone, like cortisone and all other corticoid derivatives, is capable of causing side effects, especially during long continued and/or high dosage. Some side effects produced by injudicious use of corticosteroids are: suppression of inflammation, reduction of fever, increased protein degradation and its conversion to carbohydrate leading to a negative nitrogen balance, sodium retention and potassium diuresis, retardation of wound healing, lowering of resistance to many infectious agents such as bacteria and fungi, reduction in numbers of circulating lymphocytes.

NAQUASONE may be administered to animals with acute or chronic bacterial infections providing the infections are controlled with appropriate antibiotic or chemotherapeutic agents.

It is recommended that the veterinarian determine by all practical means whether or not associated infections are present with the edema. When infections are believed to be present, one must choose the logical antimicrobial treatment and determine whether the infection should be treated first or concurrently with NAQUASONE Boluses.

It should be kept in mind that dexamethasone, like all corticosteroids, through its anti-inflammatory action may mask the signs of infection and by this action, could give a false impression of the progress of the antimicrobial treatment.

Dexamethasone is an extremely potent drug with profound physiologic effects. All of the precautions and contraindications for adrenocortical hormones must be followed. Animals receiving the drug should be under close observation.

Unless studies should prove otherwise, the possible action of dexamethasone in delaying wound healing should be kept in mind.

NAQUA® is an extremely potent nonmercurial diuretic agent required in low milligram doses for saluretic effectiveness and should be used accordingly. Electrolyte depletion effects may be seen with over vigorous therapy and maximum doses should not be used over an extended period of time. Potassium supplements have not generally been necessary with trichlormethiazide and their administration routinely should not be required. Hypochloremia is less likely with trichlormethiazide than with hydrochlorothiazide at equivalent saluretic levels. Animals with severe renal function impairments should be checked for hyperkalemia and acidosis, since therapy with benzothiadiazine diuretics like trichlormethiazide may be contraindicated in these patients.

The use of corticosteroids, depending upon dose, duration, and specific steroid, may result in the inhibition of endogenous steroid production following drug withdrawal. In patients presently receiving or recently withdrawn from systemic corticosteroid treatments, therapy with a rapidly acting corticosteroid should be considered in unusually stressful situations.

Action

The mechanism of action by which NAQUA (trichlormethiazide) effects diuresis in edematous conditions is by an inhibitory effect on the re-absorption of sodium and chloride in the renal tubules, thereby enhancing excretion of sodium chloride and water, while apparently having a considerably lessened and more temporary effect on the excretion of potassium and bicarbonate.

The corticosteroid AZIUM^® (dexamethasone) possesses remarkable anti-inflammatory and antistress activity. Clinical experience shows that udder edema is greatly reduced in many cases following parenteral treatment with 10 to 20 mg dexamethasone alone. In the majority of these cases, udder congestion is greatly reduced in 48 hours. Effective doses apparently do not cause sodium and fluid retention or potassium loss when used for a short treatment period as recommended, but rather enhance the action of the diuretic in NAQUASONE by the specific anti-inflammatory effect exerted by corticosteroids.

General Pharmacology

Trichlormethiazide is an orally administered, highly effective diuretic agent of the benzothiadiazine series. Studies in man and experimental animals show that trichlormethiazide presents a favorable pattern of less potassium excretion than chlorothiazide or hydrochlorothiazide. The clinically determined saluretic potency of trichlormethiazide is estimated to be 10 to 20 times that of hydrochlorothiazide and, correspondingly, 100 to 200 times that of chlorothiazide. Furthermore, trichlormethiazide more closely approaches the ideal saluretic agent in that sodium and chloride excretions tend to be equivalent. The possible occurrence of hypochloremic alkalosis, therefore, is lessened compared to hydrochlorothiazide with which chloride excretion in relation to sodium output may be excessive. In addition to an enhanced saluretic potency, trichlormethiazide exhibits a higher sodium to potassium ratio than either hydrochlorothiazide or chlorothiazide. The lesser potassium diuresis may be significant in decreasing the incidence of hypokalemic manifestations.

Experimental animal studies show that dexamethasone is a highly effective corticosteroid possessing remarkable anti-inflammatory activity in the bovine and other species. Veterinary clinical evidence shows dexamethasone to have anti-inflammatory activity approximately twenty times that of prednisolone in the bovine. In laboratory studies for mineralocorticoid activity (i.e., the capacity to induce retention of sodium and water in the adrenalectomized rat preparation), dexamethasone did not cause sodium or water retention.

Store between 2-30°C (36-86°F).

How Supplied

NAQUASONE Bolus; each bolus containing 200 mg trichlormethiazide and 5 mg dexamethasone, boxes of 30 and 100 boluses.

May, 1985

Nac No.

10471320