Novothyral

Package leaflet: Information for the patient

Novothyral, 100 µg + 20 µg, tablets
Levothyroxinum natricum + Liothyroninum natricum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Novothyral is and what it is used for
2. Important information before taking Novothyral
3. How to take Novothyral
4. Possible side effects
5. How to store Novothyral
6. Contents of the pack and other information

1. What Novothyral is and what it is used for

The thyroid hormones contained in Novothyral have the same action as the natural hormones
secreted by the thyroid gland. Thyroid hormones affect growth, development, and metabolism of the body.
Novothyral is used in the following cases:

• replacement therapy for hypothyroidism of any origin:
  • primary hypothyroidism (congenital or acquired, e.g. after surgical procedures, radiotherapy, or drug intake),
  • secondary hypothyroidism;
• in the euthyroid state:
  • prevention of recurrent goiter after its resection,
  • treatment of non-toxic goiter;
• suppressive and replacement therapy in malignant thyroid tumors, especially after thyroidectomy.

2. Important information before using Novothyral

When not to use Novothyral
Do not use Novothyral:

• if the patient is allergic to sodium levothyroxine, sodium liothyronine, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has untreated hypopituitarism or hyperthyroidism;
• if the patient has adrenal cortex insufficiency and is not receiving appropriate replacement therapy.

Novothyral therapy must not be initiated in cases of myocardial infarction, acute myocarditis, or acute pericarditis.
Concomitant use of levothyroxine/liothyronine and antithyroid drugs during pregnancy is contraindicated.

Warnings and precautions
Before starting Novothyral, consult a doctor or pharmacist.
Thyroid hormones should not be used for weight reduction. Taking them will not lead to weight loss if thyroid hormone levels are maintained at appropriate levels. Increasing the dose of the drug without consulting a doctor may lead to severe and life-threatening adverse effects. It is not recommended to take high doses of levothyroxine in combination with certain weight-loss drugs such as amfepramone, cathine, and phenylpropanolamine due to the possible increased risk of severe and life-threatening adverse effects.

Before starting treatment, the following conditions should be excluded or appropriately treated: coronary insufficiency, angina pectoris, arteriosclerosis, arterial hypertension, pituitary hypofunction or adrenal cortex insufficiency, and autonomous thyroid function.

If psychotic symptoms occur, the doctor may recommend more frequent monitoring and appropriate dose adjustment.
In patients with coronary insufficiency, heart failure, or cardiac arrhythmias such as tachycardia, even slight drug-induced hyperthyroidism should be avoided. In such cases, thyroid hormone levels should be monitored frequently (see dosing recommendations).

Before starting Novothyral, inform the doctor if the patient has adrenal cortex insufficiency.
In cases of secondary hypothyroidism, the underlying cause should be determined before initiating replacement therapy, and, if necessary, appropriate replacement therapy should be started in case of concomitant adrenal cortex insufficiency.

If autonomous thyroid function is suspected, the doctor will order a TRH test or a scintigraphy test with thyroid function suppression.

In the treatment of levothyroxine/liothyronine in postmenopausal women with hypothyroidism who are at increased risk of osteoporosis, thyroid function should be closely monitored to avoid supraphysiological concentrations of levothyroxine/liothyronine.

Levothyroxine/liothyronine must not be used in patients with hyperthyroidism, except in combination therapy with antithyroid drugs for the treatment of hyperthyroidism.

When initiating levothyroxine treatment in preterm infants with very low birth weight, blood pressure should be monitored regularly, as a sudden drop in blood pressure (so-called circulatory collapse) may occur.

When switching from one levothyroxine-containing medicine to another, thyroid hormone imbalance may occur. Consult the doctor if the patient has any questions regarding such a switch. Close monitoring of clinical and biochemical parameters is required during the transition period. Inform the doctor if any adverse effects occur, as dose adjustment may be necessary.

If laboratory tests to measure thyroid hormone levels are to be performed, the patient should inform the doctor or laboratory staff about current or recent biotin use (also known as vitamin H, vitamin B7, or vitamin B8). Biotin may affect laboratory test results. Depending on the type of test, results may be falsely elevated or falsely decreased due to biotin intake. The doctor may advise the patient to discontinue biotin before laboratory testing. It should also be remembered that other products taken by the patient, such as multivitamin preparations or supplements for hair, skin, and nails, may also contain biotin, which may affect laboratory test results. If the patient is taking such products, they should inform the doctor or laboratory staff (see information in section "Novothyral with other medicines").

Novothyral contains monohydrate lactose and sodium
One tablet contains 65.88 mg of monohydrate lactose. If the patient has previously been diagnosed with intolerance to certain sugars, they should consult a doctor before taking the medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

Advice for diabetic patients and patients treated with anticoagulant drugs is provided in the section Novothyral with other medicines.

Novothyral with other medicines
Inform the doctor about all medicines currently or recently used, as well as any medicines the patient plans to use.
If the patient is currently or recently taking biotin, they must inform the doctor or laboratory staff if thyroid hormone laboratory tests are to be performed. Biotin may affect laboratory test results (see "Warnings and precautions").

Antidiabetic drugs (drugs lowering blood glucose levels)
Thyroid hormones may reduce the effectiveness of antidiabetic drugs. Therefore, in diabetic patients, blood glucose levels should be monitored regularly, especially at the beginning of thyroid hormone therapy, and the dose of antidiabetic medication should be adjusted if necessary.

Anticoagulant drugs (coumarin derivatives)
Levothyroxine/liothyronine may enhance the effect of anticoagulant drugs by displacing them from plasma protein binding, thereby increasing the risk of hemorrhage into the central nervous system and gastrointestinal tract, especially in elderly patients. Therefore, coagulation parameters should be monitored regularly at the beginning of treatment (or when changing the dose) and during combined therapy. If necessary, the doctor will adjust the dose of the anticoagulant drug.

Protease inhibitors
Protease inhibitors (e.g., ritonavir, indinavir, lopinavir) may affect the action of levothyroxine. Close monitoring of thyroid hormone levels is recommended. If necessary, the doctor will adjust the dose of Novothyral.

The following drugs enhance the effect of thyroid hormones
Salicylates, dicumarol, furosemide, clofibrate
Salicylates, dicumarol, high-dose furosemide (250 mg), clofibrate, and other substances may displace levothyroxine/liothyronine from plasma protein binding, leading to increased fT levels.

Phenytoin
Phenytoin may affect the action of levothyroxine by displacing it from plasma protein binding, thus increasing fT and fT levels. Phenytoin also accelerates levothyroxine metabolism in the liver. Close monitoring of thyroid parameters is recommended.
Rapid intravenous administration of phenytoin may lead to increased serum levels of free levothyroxine and liothyronine, and in isolated cases, may increase the risk of cardiac arrhythmias.

The following drugs reduce the effect of thyroid hormones
Proton pump inhibitors
Proton pump inhibitors (such as omeprazole, esomeprazole, pantoprazole, rabeprazole, and lansoprazole) are used to reduce gastric acid production, which may impair levothyroxine absorption from the intestine and reduce its effectiveness. If the patient is taking levothyroxine during treatment with proton pump inhibitors, the doctor should monitor thyroid function and, if necessary, modify the dose of Novothyral.

Orlistat
If the patient is taking orlistat (a drug used in the treatment of obesity), or if treatment with orlistat is discontinued or changed, the patient should inform the doctor, as more frequent monitoring and appropriate dose adjustment of Novothyral may be necessary. Concomitant use of Novothyral and orlistat may lead to hypothyroidism and/or worsening of hypothyroidism control.

Sevelamer
Sevelamer may reduce levothyroxine absorption; therefore, patients should be monitored for changes in thyroid function at the beginning or end of concomitant treatment with these drugs, and the dose of Novothyral should be adjusted if necessary.

Tyrosine kinase inhibitors
Tyrosine kinase inhibitors (e.g., imatinib, sunitinib) may reduce the effectiveness of levothyroxine. Therefore, patients should be monitored for changes in thyroid function at the beginning or end of concomitant treatment with these drugs, and the dose of Novothyral should be adjusted if necessary.

Cholestyramine, colestipol
Cholestyramine or colestipol inhibit the absorption of thyroid hormones. Therefore, Novothyral should be taken 4 to 5 hours before these products.

Antacids (used to relieve indigestion), sucralfate (used in the treatment of gastric and intestinal ulcers), other aluminium-containing drugs, iron-containing drugs, calcium-containing drugs:
Novothyral should be taken at least 2 hours before such drugs, as otherwise they may reduce the effectiveness of Novothyral.

Propylthiouracil, glucocorticosteroids, β-blockers, amiodarone, and iodine-containing contrast agents
These substances inhibit the conversion of T(_4) to T(_3) in peripheral tissues.
Due to its high iodine content, amiodarone may cause both hyperthyroidism and hypothyroidism. Particular caution is advised in cases of nodular goitre with possible undiagnosed autonomous thyroid function.

Sertraline, chloroquine/proguanil
These substances reduce the effectiveness of thyroid hormones and cause increased serum TSH levels.

Drugs causing hepatic enzyme induction
Drugs causing hepatic enzyme induction, such as barbiturates (sedatives, hypnotics), carbamazepine (an antiepileptic drug also used to alleviate certain types of pain and control mood disorders), and St. John's wort-containing products (some herbal medicines), may increase hepatic clearance of levothyroxine, leading to reduced serum thyroid hormone levels.

Estrogens
During use of estrogen-containing contraceptives or postmenopausal hormone replacement therapy, the requirement for thyroid hormones may increase.

Novothyral with food and drink
The full daily dose should be taken in the morning on an empty stomach, half an hour before breakfast, without chewing the tablet, with a small amount of liquid (e.g., half a glass of water).
Soy products
Soy products may reduce intestinal absorption of Novothyral. Therefore, dose adjustment of Novothyral may be necessary, especially at the beginning or after discontinuation of soy-containing products.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a doctor before using this medicine.
The decision whether to use this medicine during pregnancy or breastfeeding will be made by the doctor.
Levothyroxine treatment should be continued consistently, especially during pregnancy and breastfeeding.

Pregnancy
An increased dose of the medicine may be required during pregnancy. Pregnant women should monitor TSH levels during each trimester of pregnancy.
Excessively high thyroid hormone levels during pregnancy may have a negative impact on the fetus and postnatal development.
Novothyral is a combination medicine containing levothyroxine and liothyronine.
The use of liothyronine during pregnancy is not recommended. If the patient plans to become pregnant or becomes pregnant, the doctor will switch treatment to levothyroxine alone, if possible.

Breastfeeding
Levothyroxine/liothyronine passes into human milk during breastfeeding; however, the concentration achieved during recommended therapeutic doses is not sufficient to cause hyperthyroidism or suppress TSH secretion in the infant.

Driving and operating machinery
No studies on the effects on the ability to drive vehicles and operate machinery have been conducted. However, since levothyroxine and liothyronine are identical to naturally occurring hormones, Novothyral is not expected to affect the ability to drive vehicles or operate machinery.

3. How to use Novothyral

This medicine should always be taken as directed by the physician. In case of doubt, consult
your doctor or pharmacist.
Individual patients may differ in their response to thyroid hormones in terms of both efficacy and tolerance; therefore, clinical monitoring of the patient and control of hormone levels are of decisive importance for treatment (liothyronine, TSH).
If adverse effects occur, the physician will reduce the daily dose or temporarily discontinue the medicine for several days.
As soon as the adverse effects subside, treatment may be continued with caution.
The following doses are recommended (guideline values):

Hypothyroidism
Children aged 4 to 12 years: ½ - 1 Novothyral tablet per day.
Adolescents and adults: ½ - 2 Novothyral tablets per day.

The usual starting dose is ½ tablet of Novothyral per day. Depending on individual tolerance, the daily dose is increased every two weeks by ½ tablet of Novothyral.

In children and patients at risk, Novothyral should be administered with extreme caution.
The physician should prescribe a low initial dose and gradually increase it at longer intervals, frequently monitoring thyroid hormone levels.

The following dosing recommendations apply to adolescents and adults:

Treatment of non-neoplastic goiter
½ - 1 Novothyral tablet per day.

Prevention of goiter recurrence after resection
½ - 1 Novothyral tablet per day.

Postoperative state following surgery due to malignant thyroid tumor
1 - 2 Novothyral tablets per day.

Elderly patients, those with low body weight, and patients with large nodular goiter generally require a lower total dose, based on clinical experience.
In elderly patients, a higher dose of levothyroxine and a lower dose of liothyronine than usual should additionally be administered.

The longer hypothyroidism has persisted and the older the patient, the more cautiously substitution therapy should be initiated, as in individual cases exacerbation of symptoms of angina pectoris in coronary heart disease or the occurrence of cardiac arrhythmias may occur.

In patients with coronary heart disease, heart failure, or tachycardia-type cardiac arrhythmias, hyperthyroidism—even to a minor degree—induced by pharmacotherapy must absolutely be avoided; therefore, in such cases, regular clinical and laboratory monitoring is essential.

The total daily dose should be taken in the morning on an empty stomach, half an hour before breakfast, without chewing the tablet, together with a small amount of liquid.

In cases of hypothyroidism and thyroidectomy due to malignant thyroid tumor, treatment is usually lifelong. In cases of euthyroid goiter and prevention of goiter recurrence, treatment duration may vary from several months to lifelong, depending on individual circumstances.

Use of a higher than recommended dose of Novothyral
If a higher than recommended dose of Novothyral is taken, seek immediate medical advice from a doctor or pharmacist.
Overdose may cause a marked increase in metabolism. Description of typical symptoms: see section 4. In predisposed patients, isolated seizures have been reported at the moment of exceeding the individual tolerance threshold.
There have been several reported cases of sudden cardiac death in individuals who chronically abused levothyroxine over many years.
If an excessive dose is taken, symptoms such as tachycardia, anxiety states, agitation, and hyperkinesis may occur.
Overdose may induce hyperthyroidism and lead to symptoms of acute psychosis.

Missed dose of Novothyral
Do not take a double dose to make up for a missed dose of Novothyral.
If a dose of Novothyral is missed, contact your doctor.

4. Possible adverse reactions

Like any medicine, Novothyral may cause adverse reactions, although not everyone experiences them.
If Novothyral is used according to recommendations and clinical and laboratory parameters are monitored, adverse reactions should not be expected.
Treatment must be discontinued and immediate consultation with a doctor or admission to the nearest hospital emergency department is required if sudden symptoms of hypersensitivity to the components of Novothyral occur: allergic reactions (rash, urticaria); angioedema (a severe allergic reaction involving swelling of the face, tongue or throat, which may cause difficulty in swallowing or breathing). The frequency of these adverse reactions is unknown.
If intolerance to the administered dose or overdose occurs, particularly if the dose is increased too rapidly at the beginning of treatment, symptoms typical of hyperthyroidism may appear, such as cardiac rhythm disturbances (including atrial fibrillation and extrasystoles), tachycardia (excessively rapid heartbeat), palpitations, angina attacks, headache, weakness and muscle cramps, hot flushes, fever, vomiting, menstrual disorders, pseudotumor cerebri, tremors, motor restlessness, insomnia, excessive sweating, weight loss, diarrhoea.
If any of the above adverse reactions occur, contact a doctor as soon as possible. The doctor will decide whether to discontinue treatment for several days or reduce the daily dose until symptoms resolve. After the adverse reactions subside, treatment may be continued with cautious dose titration.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: + 48 22 49 21 301
fax: + 48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to collect further information on the safety of the medicine.

5. How to store Novothyral

Keep this medicine out of sight and reach of children.
Do not use Novothyral after the expiry date stated on the packaging following:
Expiry date (EXP). The expiry date refers to the last day of the stated month.
Do not store above 25°C.
To protect from light and moisture, store in the outer packaging.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Novothyral contains

• The active substances are levothyroxine sodium and liothyronine sodium. Each Novothyral tablet contains: 100 micrograms of levothyroxine sodium and 20 micrograms of liothyronine sodium.
• Other components: monohydrate lactose, maize starch, gelatin, sodium croscarmellose, magnesium stearate.

What Novothyral looks like and contents of the pack
Novothyral is a white, round tablet with a break line on both sides.

Pack contains 50 or 100 tablets.
Marketing Authorisation Holder
Merck Sp. z o.o.
Al. Jerozolimskie 142B
02-305 Warsaw, Poland
tel. + 48 22 53 59 700
Logo of the marketing authorisation holder
Manufacturer
Merck Healthcare KGaA
Frankfurter Strasse 250
64293 Darmstadt, Germany