Choloxin (Dextrothyroxine Sodium)

CHOLOXIN®

Knoll

hyper

Hypolipidemic Thyroactive Agent

Action And Clinical Pharmacology: Dextrothyroxine reduces serum cholesterol levels in hyperlipidemic patients. Beta lipoprotein and triglyceride fractions may also be reduced from previously elevated levels.

Dextrothyroxine stimulates the liver to increase catabolism and excretion of cholesterol and its degradation products via the biliary route into the feces. Cholesterol synthesis is not inhibited and abnormal metabolic end-products do not accumulate in the blood.

Indications And Clinical Uses: Dextrothyroxine is an antilipidemic agent used as an adjunct to diet and other measures for the reduction of elevated serum cholesterol (low density lipoprotein) in euthyroid patients with no known evidence of organic heart disease.

Contra-Indications: Known organic heart disease, including angina pectoris; history of myocardial infarction; cardiac arrhythmia or tachycardia, either active or in patients with demonstrated propensity for arrhythmias; rheumatic heart disease; history of congestive heart failure, and decompensated or borderline compensated cardiac status.

Hypertensive states other than mild, labile systolic hypertension.

Advanced liver or kidney disease.

Pregnancy and Lactation: Contraindicated in pregnancy and lactation.

History of iodism.

Manufacturers’ Warnings In Clinical States: Several studies indicate that dextrothyroxine potentiates the effects of anticoagulants, such as warfarin or dicumarol, on prothrombin time.

Consequently, the dosage of anticoagulants should be reduced by one-third upon initiation of dextrothyroxine therapy and the dosage subsequently readjusted on the basis of prothrombin time, which should be monitored frequently during the first few weeks of treatment.

Dextrothyroxine has also apparently been shown to decrease the concentration of Factors VII, VIII, IX, and the platelet activity in some patients. Therefore, during anticoagulant therapy, attention should be paid to other clotting factors besides the one-step prothrombin time. Spontaneous bleeding has been observed in a dextrothyroxine-treated patient on warfarin who had a prothrombin time within the therapeutic range but whose prothrombin and Factor VII concentrations were greatly decreased.

Since the possibility of precipitating cardiac arrhythmias during surgery may be greater in patients treated with thyroid hormones, it may be wise to discontinue dextrothyroxine in euthyroid patients at least 2 weeks prior to an elective operation. During emergency surgery in euthyroid patients, in whom it may not be advisable to withdraw thyroid therapy, the patient should be carefully monitored.

Dextrothyroxine in diabetic patients is capable of increasing blood sugar levels with a resultant increase in requirements of insulin or oral hypoglycemic agents. Special attention should be paid to parameters necessary for good control of the diabetic state in dextrothyroxine-treated subjects and to dosage requirements of insulin or other antidiabetic drugs. If dextrothyroxine is later withdrawn from patients who had required an increase in the dosage of insulin or of other oral hypoglycemic agents during its administration, the dosage of antidiabetic drugs may again require adjustment to maintain good control of the diabetic state.

When impaired liver and/or kidney function are present, the advantages of dextrothyroxine therapy must be weighed against the possibility of deleterious results.

Precautions: General: Use of dextrothyroxine does not preclude consideration of dietary regulations in treatment of patients with hypercholesterolemia. Until more information is obtained on each effect in pediatric patients, use in children under 12 years of age is not recommended.

As with all dextrothyroxine thyroactive drugs, hypothyroid patients are more sensitive to any specified dose than euthyroid patients.

It is expected that patients on dextrothyroxine therapy will show increased serum thyronine levels. These increased serum thyronine values are evidence of absorption and transport of the drug, and should not be interpreted as evidence of hypermetabolism; therefore, they may not be used to determine the effective dose of dextrothyroxine. Thyroxine values in the range of 10 to 25 µg% in dextrothyroxine-treated patients are common.

If signs or symptoms of iodism develop during dextrothyroxine therapy, the drug should be discontinued.

The 2 mg tablets contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals to evaluate carcinogenic potential have not been performed.

Pregnancy: Teratogenic Effects: Pregnancy Category B: Reproduction studies have been performed in rabbits and rats at doses up to 100 times the expected maximum daily dose for humans and have revealed no evidence of impaired fertility or harm to the fetus due to dextrothyroxine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Women of childbearing age who require drug therapy for hypercholesterolemia should consider use of the bile acid secreting resins. Since pregnancy may occur despite use of birth control procedures, administration of dextrothyroxine to women of this age group should be undertaken only after weighing the possible risk to the fetus against the possible benefits to the mother.

Lactation: It is not known whether dextrothyroxine is excreted in human milk. Because many drugs are excreted in human milk, caution and careful monitoring of the nursing infant should be exercised when dextrothyroxine is administered to a nursing woman.

Children: Safety and effectiveness in children have not been established.

Drug Interactions: Additive metabolic effects may occur when dextrothyroxine is administered concomitantly with other thyroid preparations.

Dextrothyroxine may potentiate the anticoagulant effects of warfarin sodium or dicumarol. When either of these drugs is administered concurrently with dextrothyroxine, the dosage of the oral anticoagulant initially should be reduced by one-third to prevent hemorrhage. Frequent prothrombin time determinations should be performed (at least weekly during the first few weeks of therapy), and anticoagulant dosage should be adjusted as needed.

Dextrothyroxine may enhance the effects of cardiac glycosides on the myocardium, resulting in excessive myocardial stimulation.

Administration of catecholamines in patients with coronary artery disease may precipitate arrhythmias and/or coronary insufficiency. Because this reaction may be enhanced in patients receiving thyroid preparations, catecholamines should be given with extreme caution in patients with coronary artery disease who are receiving dextrothyroxine.

Cholestyramine resin, and possibly colestipol HCl, may decrease the absorption of concurrently administered thyroid preparations. Patients should be instructed to allow as long a time interval as possible between ingestion of dextrothyroxine and the resins. Some clinicians recommend that dextrothyroxine be administered at least 1 hour before or 4 hours after the resins.

Dextrothyroxine may increase blood glucose concentrations and cause glycosuria in patients with diabetes mellitus, thus necessitating close monitoring and possibly an increase in dosage of insulin or oral antidiabetic drugs during concomitant therapy. If dextrothyroxine is discontinued in a patient who required an increased dosage of hypoglycemic drugs, dosage of the hypoglycemic drug should be reduced and subsequently adjusted to maintain control of the diabetic state.

Adverse Reactions: The side effects attributed to dextrothyroxine therapy may be minimized by following the recommended dosage schedule. Adverse effects are least commonly seen in euthyroid patients with no signs or symptoms of organic heart disease. The incidence of adverse effects is increased in hypothyroid patients and is highest in those patients with organic heart disease superimposed on the hypothyroid state.

The single side effect that has caused the most concern is the possibility of increased severity of frequency of angina in patients with coronary artery disease.

In the absence of known organic heart disease, some cardiac signs and symptoms have occurred during dextrothyroxine therapy. In addition to angina pectoris, arrhythmias consisting of extrasystoles, ectopic beats, or supraventricular tachycardia, ECG evidence of ischemic myocardial changes, and increase in heart size have been observed. Myocardial infarctions, both fatal and nonfatal, have occurred, but these are not unexpected in untreated patients in the age groups studied. It is not known whether any of these infarcts were drug related.

Changes in clinical status that may be related to the metabolic action of the drug include the development of insomnia, nervousness, palpitation, tremors, loss of weight, lid loss, sweating, flushing, hyperthermia, hair loss, diuresis, and menstrual irregularities. Gastrointestinal complaints during therapy have included dyspepsia, abdominal pain, nausea and vomiting, constipation, diarrhea, and decrease in appetite.

Other side effects reported to be associated with dextrothyroxine therapy include the development of headache, changes in libido (increase or decrease), hoarseness, tinnitus, dizziness, peripheral edema, malaise, tiredness, visual disturbances, psychological changes, paresthesia, muscle pain, and various bizarre subjective complaints. Skin rashes, including a few that appeared to be due to iodism, and itching, have been attributed to dextrothyroxine by some investigators.

Gallstones have been discovered in occasional dextrothyroxine-treated patients and cholestatic jaundice has occurred in 1 patient, although its relationship to dextrothyroxine therapy has not been established.

In several instances, the previously existing conditions of the patient appeared to continue or progress during the administration of dextrothyroxine. A worsening of peripheral vascular disease, sensorium, exophthalmos, and retinopathy have been reported.

Several clinicians have reported that dextrothyroxine potentiates the effect of anticoagulants, such as warfarin or dicoumarol on prothrombin time, thus indicating a decrease in the dosage requirements of the anticoagulants. On the other hand, dosage requirements of antidiabetic drugs have been reported to be increased during dextrothyroxine therapy (see Warnings).

Cerebrovascular accidents, thrombophlebitis, and gastrointestinal hemorrhages in patients who were not receiving anticoagulants have occurred but there appears to be no relationship between these developments and dextrothyroxine therapy.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdosage with dextrothyroxine may result in signs and symptoms of thyrotoxicosis. The dosage at which such symptoms may appear will depend on the previous thyroid status of the patient and his/her individual sensitivity to the drug. Dextrothyroxine is predominantly protein-bound and would not be expected to be appreciably dialyzable; however, no direct information is available. Treatment of overdosage is similar to that of thyrotoxic storm and may include hydration, sedation, and use of beta-adrenergic blocking agents.

Dosage And Administration: For most hypercholesterolemic patients, the recommended maintenance dose of dextrothyroxine is 4 to 6 mg administered as a single oral dose daily, although the effective dosage range is 2 to 8 mg/day. The initial daily dose should be 1 to 2 mg, to be increased in 1 to 2 mg increments at intervals of not less than 1 month, to a maximum level of 4 to 8 mg daily, if that dosage is indicated to effect the desired lowering of serum cholesterol.

If signs or symptoms of cardiac disease or iodism develop during the treatment period, the drug should be withdrawn.

Hypothyroid patients are more sensitive to any specified dose of dextrothyroxine than are euthyroid patients. The initial dose should not exceed 1 mg. Dosage may be increased by 1 mg increments at intervals of not less than 1 month. The maximum daily dose generally should not exceed 4 mg.

Availability And Storage: 2 mg: Each orange, scored tablet, contains: dextrothyroxine sodium 2 mg. Nonmedicinal ingredients: acacia, confectioners’ sugar, FD&C Yellow No. 5 (tartrazine), gelatin, lactose, magnesium stearate, polysorbate 80, povidone and talc. Packages of 100.

4 mg: Each white, scored tablet, contains: dextrothyroxine sodium 4 mg. Nonmedicinal ingredients: confectioners’ sugar, gelatin, lactose, magnesium stearate, povidone and talc. Packages of 100.

Store at controlled room temperature 15 to 30°C. Dispense in well-closed containers as described in USP.

CHOLOXIN® Knoll Dextrothyroxine Sodium Hypolipidemic Thyroactive Agent

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Hypercholesterolemia

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