Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mercury Pharmaceuticals Ltd, Capital House, 85 King William Street, London EC4N 7BL, UK
Levothyroxine should be introduced very gradually in patients aged over 50 years (see section 4.2) and those with long standing hypothyroidism to avoid any sudden increase in metabolic demands.
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.
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.
See note above regarding withdrawal of treatment.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Subclinical hyperthyroidism may be associated with bone loss. To minimise the risk of osteoporosis, dosage of levothyroxine sodium should be titrated to the lowest possible effective level.
Parents of children receiving thyroid agent should be advised that partial loss of hair may occur during the first few months of therapy, but this effect is usually transient and subsequent regrowth usually occurs.
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.
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.
Blood sugar levels are raised and dosage of anti-diabetic agents may require adjustment.
Tricyclic anti-depressants (e.g. amitriptyline, imipramine, dosulepin) response may be accelerated because levothyroxine increases sensitivity to catecholamines; concomitant use may precipitate cardiac arrhythmias.
The effects of sympathomimetic agents (e.g. adrenaline or phenylephrine) are also enhanced
Cardiac glycosides: 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.
NSAIDs: False low plasma concentrations have been observed with concurrent anti-inflammatory treatment such as phenylbutazone or acetylsalicylic acid and levothyroxine therapy.
Beta Blockers: levothyroxine (thyroxine) accelerates metabolism of propranolol, atenolol and sotalol.
General anaesthetics: Isolated reports of marked hypertension and tachycardia have been reported with concurrent ketamine administration.
Amiodarone may inhibit the de iodination of thyroxine to tri iodothyronine resulting in a decreased concentration of tri iodothyronine, thereby reducing the effects of thyroid hormones.
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.
Effects of Levothyroxine may be decreased by concomitant sertraline.
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).
Metabolism of levothyroxine (thyroxine) accelerated by rifampicin, barbituarates, and primidone. (may increase requirements for levothyroxine (thyroxine) in hypothyroidism)
Imatinib: plasma concentration of levothyroxine (thyroxine) possibly reduced by imatinib.
Beta blockers may decrease the peripheral conversion of levothyroxine to triiodothyronine.
Lipid regulating drugs: Lovastatin has been reported to cause one case each of hypothyroidism and hyperthyroidism in two patients taking levothyroxine.
Sex Hormones: 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-obesity drugs such as orlistat may decrease levothyroxine absorption which may result in hypothyroidism (monitor for changes in thyroid function).
A number of drugs may affect thyroid function tests and this should be borne in mind when monitoring a patient on levothyroxine therapy.
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.
The safety of Levothyroxine treatment during pregnancy is not known, but any possible risk of foetal abnormalities should be weighed against the risk to the foetus of untreated hypothyroidism.
Levothyroxine is excreted in breast milk in low concentrations, and it is contentious whether this can interfere with neonatal screening.
Levothyroxine has no or negligible 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.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
None known.
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