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`LTR-PO4
`rillainna
`LABORATORIES"
`LEVOTHYROXINE SODIUM FOR INJECTION
`Rx ONLY.
`
`DESCRIPTION
`Levothyroxine Sodium for Injection contains synthetic crystalline levothyroxine sodium (L-
`thyroxine). L-thyroxine is the principal hormone secreted by the normal thyroid gland.
`Levothyroxine sodium is chemically designated as 1-tyrosine, 0-(4-hydroxy-3,5-diiodophenyI)-
`3,5-diiodo-monosodium salt and has the following structural formula:
`
`O
`
`798.86
`C15H1014NNa04 (cid:9)
`Levothyroxine Sodium for Injection is a sterile, lyophilized product and is available in two strengths: 200
`or 500 mcg/vial. Each vial also contains mannitol 10 mg and tribasic sodium phosphate anhydrous 0.7
`mg. Sodium hydroxide added for pH adjustment.
`CLINICAL PHARMACOLOGY
`Levothyroxine Sodium for Injection is effective by parenteral route. Following absorption, the synthetic
`L-thyroxine provided by levothyroxine sodium cannot be distinguished from L-thyroxine that is secreted
`endogenously. Each is bound to the same serum proteins forming a reservoir of circulating L-thyroxine.
`Levothyroxine sodium will provide L-thyroxine (T4 as a substrate for physiologic deiodination to L-
`triiodothyronine (T3). Therefore, patients taking properly adjusted doses of levothyroxine sodium will
`demonstrate normal blood levels of L-triiodothyronine even when the thyroid gland has been removed
`surgically or destroyed by radioiodine. Administration of Levothyroxine Sodium for Injection alone will
`result in complete physiologic thyroid replacement.
`INDICATIONS AND USAGE
`Levothyroxine Sodium for Injection serves as specific replacement therapy for reduced or absent
`thyroid function of any etiology. Levothyroxine Sodium for Injection can be used intravenously (IV)
`whenever a rapid onset of effect is critical, and either IV or intramuscularly (IM) in hypothyroid patients
`whenever the oral route is precluded for long periods of time.
`CONTRAINDICATIONS
`There are no absolute contraindications to levothyroxine sodium therapy. Relative contraindications include
`acute myocardial infarction, uncorrected adrenal insufficiency and thyrotoxicosis (see WARNINGS).
`WARNINGS
`Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been
`used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal
`requirements are ineffective for weight reduction. Larger doses may produce serious or even life-
`threatening manifestations of toxicity, particularly when given in association with sympathomimetic
`amines such as those used for their anorectic effects.
`
`Patients with cardiovascular diseases warrant particularly close attention during the restoration of
`normal thyroid function by any thyroid drug. In such cases, low initial dosage increased slowly by small
`increments is indicated. Occasionally, the cardiovascular capacity of the patient is so compromised that
`the metabolic demands of the normal thyroid state cannot be met. Clinical judgement will then dictate
`a less than complete restoration of thyroid status.
`Endocrine disorders such as diabetes mellitus, adrenal insufficiency (Addison's disease),
`hypopituitarism and diabetes insipidus are characterized by signs and symptoms which may be
`diminished in severity or obscured by hypothyroidism. Levothyroxine sodium therapy for such patients
`may aggravate the intensity of previously obscured symptoms and require appropriate adjustment of
`therapeutic measures directed at these concomitant disorders.
`Thyroid replacement may potentiate the effects of anticoagulants. Patients on anticoagulant therapy
`should have frequent prothrombin determinations when instituting thyroid replacement to gauge the
`need to reduce anticoagulant dosage.
`
`PRECAUTIONS
`Overdosage with any thyroid drug may produce the signs and symptoms of thyrotoxicosis, but
`resistance to such factitious thyrotoxicosis is the general rule.
`Close observation of the patient following the administration of Levothyroxine Sodium for Injection is
`advised, and appropriate adjustment of repeated dosage is recommended.
`ADVERSE REACTIONS
`Adverse reactions are due to overdose and induced hyperthyroidism.
`DOSAGE AND ADMINISTRATION
`Levothyroxine Sodium for Injection by IM or IV routes can be substituted for the oral dosage form when
`ingestion of tablets is precluded for long periods of time. The initial parenteral dosage should be
`approximately one half of the previously established oral dosage of levothyroxine sodium tablets. A
`daily maintenance dose of 50 to 100 mcg parenteraily should suffice to maintain the euthyroid state,
`once established. Close observation of the patient, with individual adjustment of the dosage as needed,
`is recommended.
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`Mylan Ex 1053, Page 1
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`In infants and children, there is great urgency to achieve full thyroid replacement because of the critical
`importance of thyroid hormone in sustaining growth and maturation. Despite the smaller body size, the
`dosage needed to sustain a full rate of growth, development and general thriving is higher in the child
`than in the adult.
`Optimal maintenance levels should be adjusted individually to obtain normal serum T3, T4, free T4, index
`and Thyroid Stimulating Hormone (TSH) values after several weeks of therapy for hypothyroidism. The
`patent's clinical status is most important and some patents may be clinically euthyroid with individual
`laboratory values that are not within normal range (i.e., elevated total T4 with normal T3). An exception
`may be seen in congenital hypothyroidism where elevated serum TSH values may persist for the first
`two to three years of life despite normalization of free T4 measurements. In such cases, it generally is
`recommended that maintenance of normal serum free T4 values alone should be considered
`therapeutically sufficient.
`In myxedema coma or stupor, without concomitant severe heart disease, 200 to 500 mcg of
`Levothyroxine Sodium for Injection may be administered IV as a solution containing 100 mcg/mL. DO
`NOT ADD TO OTHER IV FLUIDS. Although the patient may show evidence of increased responsivity
`within six to eight hours, full therapeutic effect may not be evident until the following day. An additional
`100 to 300 mcg or more may be given on the second day if evidence of significant and progressive
`improvements has not occurred. Levothyroxine Sodium for Injection produces a predictable increase in
`the reservoir level of hormone with a seven day half-life. This usually precludes the need for multiple
`injections but continued daily administration of lesser amounts parenterally should be maintained until
`the patient is fully capable of accepting a daily oral dose.
`In the presence of concomitant heart disease, the sudden administration of such large doses of L-
`thyroxine IV is clearly not without its cardiovascular risks. Under such circumstances, IV therapy should
`not be undertaken without weighing the alternative risks of the myxedema coma and the cardiovascular
`disease. Clinical judgement in this situation may dictate smaller IV doses of Levothyroxine Sodium for
`Injection.
`The age and general physical condition of the patient and the severity and duration of hypothyroid
`symptoms determine the starting dosage and the rate of incremental dosage increase leading to a final
`maintenance dosage. Clearly it is the physician's judgment of the severity of the disease and closer
`observation of patient response which determine the rate and extent of dosage increase.
`Appropriate laboratory tests are beneficial in monitoring thyroid replacement therapy. Although
`measurements of normal blood levels of thyroxine in patients on oral replacement regimens frequently
`coincide with clinical impressions of normal thyroid status, higher than normal levels occur occasionally
`and should not be considered evidence of overdosage per se. In all cases, clinical impressions of the
`well being of the patient take precedence over laboratory determination of appropriate individual
`dosage.
`Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
`administration, whenever solution and container permit.
`
`HOW SUPPLIED
`
`NDC Number
`NDC 55390-880-10
`
`Levothyroxine Sodium for Injection 200 mcg/vial (cid:9)
`in individually-boxed 10 mL flip-top vials.
`Levothyroxine Sodium for Injection 500 mcg/vial (cid:9)
`in individually-boxed 10 mL flip-top vials.
`Store dry product at controlled room temperature 15° to 30°C (59° to 86°F). Protect from light.
`RECONSTITUTION DIRECTIONS
`Reconstitute the lyophilized levothyroxine sodium by aseptically adding 5 mL of 0.9% Sodium Chloride
`Injection, USP only. Reconstituted concentrations for the 200 mcg and 500 mcg vials are 40 mcg/mt..
`and 100 mcg/mL, respectively. Shake vial to insure complete mixing. Use Immediately after
`reconstitution. Do not add to other IV fluids. Discard any unused portion.
`
`NDC 55390-881-10
`
`Manufactured for Bedford Laboratories TM, Bedford, OH 44146
`Manufactured by Ben Venue Laboratories, Inc., Bedford, OH 44146
`
`May 2003
`LTR-PO4
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`Mylan Ex 1053, Page 2
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