Chemical formula: C₁₅H₁₁I₄NO₄ Molecular mass: 776.87 g/mol PubChem compound: 5819
Levothyroxine interacts in the following cases:
False low plasma concentrations of levothyroxine have been observed with concurrent anti-inflammatory treatment such as phenylbutazone or acetylsalicylic acid and levothyroxine therapy.
Absorption of levothyroxine (thyroxine) possibly reduced by antacids, proton pump inhibitors, calcium salts, cimetidine, oral iron, sucralfate, colestipol, polystyrene sulphonate resin and cholestyramine (administration should be separated by 4-5 hours).
Blood sugar levels are raised and dosage of anti-diabetic agents may require adjustment. Thyroid replacement therapy may cause an increase in dosage requirements of insulin or other anti-diabetic therapy (such as metformin). Care is needed for patients with diabetes mellitus, and diabetes insipidus.
Levothyroxine increases the effect of anticoagulants (warfarin) and it may be necessary to reduce the anticoagulation dosage if excessive, hypoprothrombinaemia and bleeding are to be avoided.
If levothyroxine therapy is initiated in digitalised patients, the dose of digitalis may require adjustment. Hyperthyroid patients may need their digoxin dosage gradually increased as treatment proceeds because initially patients are relatively sensitive to digoxin.
Beta blockers may decrease the peripheral conversion of levothyroxine to triiodothyronine.
Oestrogen, oestrogen containing product (including hormone replacement therapy) and oral contraceptives may increase the requirement of thyroid therapy dosage. Conversely, androgens and corticosteroids may decrease serum concentrations of levothyroxine-binding globulins.
Anti-convulsants, such as carbamazepine and phenytoin, enhance the metabolism of thyroid hormones and may displace them from plasma proteins.
Initiation or discontinuation of anti-convulsant therapy may alter levothyroxine dosage requirements.
Tricyclic anti-depressants (e.g. amitriptyline, imipramine, dosulepin) response may be accelerated because levothyroxine increases sensitivity to catecholamines; concomitant use may precipitate cardiac arrhythmias.
Amiodarone may inhibit the de iodination of thyroxine to triiodothyronine resulting in a decreased concentration of tri iodothyronine, thereby reducing the effects of thyroid hormones.
Colestyramine reduces the absorption of levothyroxine.
Plasma concentration of levothyroxine (thyroxine) possibly reduced by imatinib.
Isolated reports of marked hypertension and tachycardia have been reported with concurrent ketamine administration with levothyroxine.
Lovastatin has been reported to cause one case each of hypothyroidism and hyperthyroidism in two patients taking levothyroxine.
Anti-obesity drugs such as orlistat may decrease levothyroxine absorption which may result in hypothyroidism (monitor for changes in thyroid function).
Levothyroxine (thyroxine) accelerates metabolism of propranolol, atenolol and sotalol.
Raloxifene reduces the absorption of levothyroxine.
Metabolism of levothyroxine (thyroxine) accelerated by rifampicin, barbituarates, and primidone (may increase requirements for levothyroxine (thyroxine) in hypothyroidism).
Post-marketing cases have been reported indicating a potential interaction between ritonavir containing products and levothyroxine. Thyroid-stimulating hormone (TSH) should be monitored in patients treated with levothyroxine at least the first month after starting and/or ending ritonavir treatment.
Effects of levothyroxine may be decreased by concomitant sertraline.
Patients with panhypopituitarism or other causes predisposing to adrenal insufficiency may react to levothyroxine treatment, and it is advisable to start corticosteroid therapy before giving levothyroxine to such patients.
Levothyroxine sodium should be used with caution in patients with cardiovascular disorders, including angina, coronary artery disease, hypertension, and in the elderly who have a greater likelihood of occult cardiac disease.
To minimise the risk of adverse effects of undetected overtreatment, such as atrial fibrillation and fractures associated with low serum levels of thyroid stimulating hormone (TSH) in older patients, it is important to monitor serum TSH and adjust the dose accordingly during long term use.
In individuals suspected to have cardiovascular disease or to be at high risk, it is important to perform an ECG prior to commencement of levothyroxine treatment in order to detect changes consistent with ischaemia in which case, levothyroxine should be initiated at a low dose, followed by cautious dose escalation to avoid worsening of ischaemia or precipitation of an infarct.
Special care is needed for the elderly and for patients with symptoms of myocardial insufficiency, or ECG evidence of myocardial infarction.
Care is required when levothyroxine is administered to patients with known history of epilepsy. Seizures have been reported rarely in association with the initiation of levothyroxine sodium therapy and may be related to the effect of thyroid hormone on seizure threshold.
Women on a maintenance dose for hypothyroidism who become pregnant, must be monitored closely. Levothyroxine sodium does not readily cross the placenta in the second and third trimester, but may do so in the first. Levothyroxine sodium is not known to have either carcinogenic or teratogenic effects.
Treatment with levothyroxine should be given consistently during pregnancy and breast-feeding in particular. Dosage requirements may even increase during pregnancy.
Experience has shown that there is no evidence of drug-induced teratogenicity and/or foeto-toxicity in humans at the recommended therapeutic dose level. Excessively high dose levels of levothyroxine during pregnancy may have a negative effect on foetal and postnatal development.
Combination therapy of hyperthyroidism with levothyroxine and anti-thyroid agents is not indicated in pregnancy. Such combination would require higher doses of anti-thyroid agents, which are known to pass the placenta and to induce hypothyroidism in the infant.
Thyroid suppression diagnostic tests should not be carried out during pregnancy, as the application of radioactive substances in pregnant women is contraindicated.
Levothyroxine is secreted into breast milk during lactation but the concentrations achieved at the recommended therapeutic dose level are not sufficient to cause development of hyperthyroidism or suppression of TSH secretion in the infant. Levothyroxine can be used during lactation.
There are no fertility data available.
No studies on the effects on the ability to drive and use machines have been performed. However, since levothyroxine is identical to the naturally occurring thyroid hormone, it is not expected that levothyroxine has any influence on the ability to drive and use machines.
Side-effects are usually indicative of excessive dosage and usually disappear on reduction of dosage or withdrawal of treatment for a few days. Adverse reactions listed below have been observed during clinical studies and/or during marketed use and are based on clinical trial data and classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention: Not known (cannot be estimated from the available data)
Not known: Hypersensitivity reaction
Not known: Thyrotoxic crisis1
Not known: Restlessness, agitation, insomnia
Not known: Tremor
Not known: Angina pectoris, arrhythmia, palpitations, tachycardia
Not known: Flushing
Not known: Dyspnoea
Not known: Diarrhoea, vomiting
Not known: Hyperhidrosis, rash, pruritus
Not known: Arthralgia, muscle spasm, muscular weakness
Not known: Menstruation irregular
Not known: Headache, pyrexia, malaise, oedema
Not known: Weight decreased
1 Some patients may experience a severe reaction to high levels of thyroid hormone. This is called a “thyroid crisis” with any of the following symptoms: Hyperpyrexia, tachycardia, arrhythmia, hypotension, cardiac failure, jaundice, confusion, seizure and coma
Heat intolerance, transient hair loss, benign intracranial hypertension, craniostenosis in infants and premature closure of epiphysis in children.
The following side effects are usually due to excessive dosage, and correspond to symptoms of hyperthyroidism: arrhythmias, anginal pain, tachycardia, disorders of menstruation, pseudotumor cerebri, cramps in skeletal muscles, headache, restlessness, excitability, flushing, sweating, diarrhoea, excessive weight loss and muscular weakness, insomnia, tremor, fever, vomiting, palpitations and heat intolerance.
These reactions usually disappear after dose reduction or withdrawal of treatment.
Hypersensitivity reactions including rash, pruritus and oedema have also been reported.
Thyroid crisis have occasionally been reported following massive or chronic intoxication and cardiac arrhythmias, heart failure, coma and death have occurred.
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