Levothyroxine dosage

Kabadi UM. Influence of age on optimal daily levothyroxine dosage in patients with primary hypothyroidism grouped according to etiology. South Med J 1997 90 920-924. 

The general importance of this interaetion is not known, but be alert for the need to increase the levothyroxine dosage in any patient given antae-ids. More study is needed. See also ealcium carbonate , (below), whieh can reduce levothyroxine effects. 

A patient with hypothyroidism had been successfully managed with 150 micrograms of levothyroxine daily for 4 years, developed hypothyroidism when given 300 mg of phenytoin daily. Doubling the levothyroxine dosage proved to be effective. Later this interaction was confirmed when stopping and restarting the phenytoin produced the same effect. ... 

Despite very clear evidence that both carbamazepine and phenytoin can cause a marked reduction in endogenous serum thyroid hormone levels, the development of clinical hypothyroidism seems to be very rare, and there seems to be only one case on record of an interaction between levothyroxine and phenytoin. There seems to be little reason for avoiding concurrent use, but the outcome should be monitored. Increase the levothyroxine dosage if necessary. Consider also Thyroid hormones + Barbiturates , below. 

A man needed to have his levothyroxine dosage doubled when he took ritonavir/saquinavir, and another woman possibly had a similar reaction when given indinavir then nelfinavir. Conversely, another woman needed a markedly reduced dose of levothyroxine when given indinavir. 

Fourteen patients with primary hypothyroidism had an increase in TSH levels from 1.6 to 5.4 mU/L when given ferrous sulfate 300 mg daily for 12 weeks along with their usual levothyroxine dose. The symptoms of hypothyroidism in 9 patients worsened. In another report a woman with hypothyroidism, taking levothyroxine, had a very marked rise in TSH levels when she took ferrous sulfate. Her levothyroxine dosage needed to be raised from 175 to 200 micrograms daily. ... 

Nine patients with hypothyroidism were noted to have elevated TSH levels (indicating a decrease in the efficacy of their treatment with levothyroxine, when they also received sertraline. Two other patients with thyroid cancer, whose TSH levels had been deliberately depressed, developed TSH levels in the normal range while taking sertraline. None of the patients showed any signs of hypothyroidism at the time, and all of them had been taking the same dose of levothyroxine for at least 6 months. TSH levels of up to almost 17 mU/L (normal range 0.3 to 5 mU/L) were seen in some patients. The levothyroxine dosages were increased by 11 to 50%, until the TSH levels were back to normal. The authors of this report say that they know of 3 patients whose TSH levels were unaltered by sertraline. ... 

A 29-year-old female who takes levothyroxine following her thyroidectomy becomes pregnant If the dosage is not changed, she will become... 

Levothyroxine is used to treat hypothyroidism (an underactive thyroid gland). Thyroid hormone can be made from beef and pork thyroid, but this lacks standardization and it is difficult to control dosage. The synthetic drug is more desirable. Levothyroxine is one of two important thyroid hormones. It is converted into the second important hormone, liothyronine, in the body. The key step in the synthesis of structures such as levothyroxine is the substitution of an iodonium salt by an iodinated phenol. Siql-like reactions on an aromatic ring are not common, but an iodonium salt provides a good leaving group. 

Dosage adjustment The levothyroxine dose generally is adjusted in 12.5 to 25 meg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized. 

Exchange therapy - Nhen switching a patient to liothyronine from thyroid levothyroxine or thyroglobulin, discontinue the other medication, initiate liothyronine at a low dosage, and increase gradually according to the patient s response. Liothyronine has a rapid onset of action and that residual effects of the other thyroid preparation may persist for the first several weeks of therapy. 

The frequency of TSH monitoring during levothyroxine dose titration is generally recommended at 6- to 8-week intervals until normalization. For patients who have recently initiated levothyroxine therapy and whose serum TSH has normalized or in patients who have had their dosage or brand of levothyroxine changed, measure the serum TSH concentration after 8 to 12 weeks. 

Bauer et al. (126) entered 11 rapid-cycling, treatment-refractory patients into an open trial of high-dose levothyroxine sodium, added to their previously stabilized medication regimen. The dosage of the levothyroxine was increased by 0.05 to 0.1 mg/day every 1 to 2 weeks, as tolerated, until symptoms improved or adverse effects prevented further increases. Scores on both the depressive and the manic symptom rating scales decreased significantly compared with baseline scores. 

Both the thiouracils and thioimidazoles readily cross the placenta and can cause fetal hypothyroidism, resulting in a slight delay in neurological or bone maturation. Various degrees of goiter have also been observed, even to the extent of severe tracheal compression and death. Antithyroid drug dosage should therefore be reduced to the minimum required to maintain a euthyroid state without supplementation of levothyroxine (93). 

As with all forms of long-term therapy, adherence to the prescribed dosage of levothyroxine is not always optimal, and an unwarranted fear of thyroid-induced osteoporosis can add to this lack of adherence. Inadequacy of thyroxine replacement therapy is not always easily recognized. Several patients were reported with clearly inadequate or excessive consumption of levothyroxine despite a correct prescription. All patients had depression, which could be an additional susceptibility factor by promoting lack of adherence, and the resulting hypothyroidism or hyperthyroidism could further aggravate the depression (12). 

Two patients with hypothyroidism taking a fixed dosage of levothyroxine took aluminium hydroxide and magnesium oxide (72). In both cases there was a marked increase in the serum concentration of TSH and low serum T4. After withdrawal of the antacids, TSH again fell. In vitro studies showed a dose-related adsorption of levothyroxine by a combination of aluminium hydroxide, magnesium hydroxide, and magnesium carbonate, but no effect of magnesium oxide alone. 

Reactivation of the autoimmune process may occur when the dosage of antithyroid drug is lowered during maintenance therapy and TSH begins to drive the gland. TSH release can be prevented by the daily administration of 50-150 ag of levothyroxine with 5-15 mg of methimazole or 50-150 mg of propylthiouracil for the second year of therapy. The relapse rate with this program is probably comparable to the rate with antithyroid therapy alone, but the risk of hypothyroidism and overtreatment is avoided. 

Several cases of mania have been reported even after dosages of levothyroxine that are usually considered safe (616). 

Previous case reports have suggested that psychosis and mania can be the result of starting thyroid hormone replacement at too high a dosage (617). Two further cases of mania associated with levothyroxine have been reported (618,619), suggesting that caution should be exercised when prescribing levothyroxine, especially in elderly people. 

The main indication for levothyroxine is treatment of deficiency (cretinism, and adult hypoth5n-oidism) from any cause. The adult requirement of hormone is remarkably constant, and dosage does not usually have to be altered once the optimum is foimd. Patients should be monitored at annual intervals. Monitoring needs to be more frequent in children, who may need more as they grow. Similarly, pregnant women should be monitored monthly, and require 50-100% increase in their normal dose of levothyroxine. 

Adverse effects of thyroid hormone parallel the increase in metabolic rate. The symptoms and signs are those of hyperthyroidism. Symptoms of myocardial ischaemia, atrial fibrillation or heart failure are liable to be provoked by too vigorous therapy or in patients having serious ischaemic heart disease who may even be unable to tolerate optimal therapy. Should they occur levothyroxine must be discontinued for at least a week and begim again at lower dosage. Only slight overdose is needed to precipitate atrial fibrillation in patients over 60 years. 

Induction of cytochrome P450 may be the explanation for a modest increase in the clearance of levothyroxine (10-15%) which may necessitate an increase in dosage. In two cases, rifampicin led to significant increases in TSH concentrations in patients being treated for hypothyroidism (30). 

The optimal dosage of levothyroxine should be based on repeated measurements of T3 and TSH serum concentrations. The daily recommended dose depends on the aim of the therapy. Thyroid replacement therapy for control of spontaneous or iatrogenic hypothyroidism should aim at a dosage of levothyroxine that maintains TSH concentrations within the low reference range. This will usually be associated with a free T4 concentration in the high reference range and a T3 concentration within the reference range. The mean requirement for such patients is... 

---