Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Rare Thyroid Therapeutics International AB, Klara Norra Kyrkogata 26, 111 22, Stockholm, Sweden
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hyperthyroidism for other reasons than MCT8 deficiency (e.g. Grave’s Disease).
Pregnancy (see section 4.6).
At initiation of Emcitate treatment and/or during dose titration, new onset or worsening of hypermetabolic signs and symptoms, such as hyperhidrosis, irritability, anxiety, insomnia, nightmares, hyperthermia, tachycardia, transient elevations in systolic blood pressure (SBP), or diarrhoea, may occur (see section 4.8). These signs and symptoms are usually transient and resolve spontaneously within a few days. If hypermetabolic signs and symptoms do not resolve within 2 weeks, the dose should be reduced according to the steps in the dose titration regimen (see section 4.2). Following the resolution of hypermetabolic signs and symptoms, dose titration may be resumed, as clinically appropriate.
Caution should be used during dose titration in patients with cardiac disease, as they may be at increased risk of adverse reactions associated with a hypermetabolic state (see section 4.8).
Tiratricol cross-reacts with T3 if assessed by immunoassay, which may cause unreliable test results. It is recommended to use an LC/MS/MS method to measure T3 levels. Care should be taken if an immunoassay method is used. Specific guidelines should be followed for interpreting T3 test results when determining or adjusting the dose of tiratricol (see section 4.2).
Caution should be used in patients with diabetes (see section 4.5).
The safety and efficacy of Emcitate in patients with hepatic impairment have not been studied. Special care is required in these patients (see section 4.2).
The safety and efficacy of Emcitate in patients with renal impairment have not been studied. Special care is required in these patients (see section 4.2).
Tiratricol should not be taken for weight reduction. It may cause serious or life-threatening undesirable effects, particularly in combination with orlistat (see section 4.5 under “Orlistat”).
Emcitate tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
No clinical interaction studies have been performed evaluating the effect of other medicinal products on tiratricol. The potential interactions described below are based on the in vitro characterisation of tiratricol and on known pharmacokinetic or pharmacodynamic interactions of thyromimetic agents with other medicinal products and not specifically studied with tiratricol.
Antacids, charcoal, calcium, cationic resins (e.g. cholestyramine), iron, sucralphate, and other gastrointestinal agents may interfere with the gastrointestinal absorption of tiratricol. These treatments should be taken before or after tiratricol (more than 2 hours before or after if possible). In the case of cholestyramine, tiratricol should be taken 1 hour before or 4 hours after the resin dose. Adjustment of the tiratricol dose may be required to obtain the desired effect.
Co-administration with PPIs may cause a decrease in the absorption of the thyroid hormones, due to the increase of the intragastric pH caused by PPIs such as omeprazole, esomeprazole, pantoprazole, rabeprazole and lansoprazole. Serum concentrations of T3 should be monitored and dose adjustment of tiratricol considered when initiating, changing or discontinuing PPI treatment.
Sevelamer may decrease the concentration of thyroid hormones and result in reduced efficacy of tiratricol. Sevelamer should be taken more than 2 hours before or after administration of tiratricol.
Medicinal products that can induce the enzyme system in the liver, such as barbiturates, phenytoin carbamazepine, rifabutin, rifampicin or products containing St. John’s wort (Hypericum perforatum) may increase the hepatic clearance of tiratricol. Serum concentrations of T3 should be monitored and dose adjustment of tiratricol considered when initiating, changing or discontinuing an antiepileptic treatment regimen or other enzyme inducing agents.
Concomitant use of tiratricol and antimalarial medicinal products (chloroquine, proguanil) may cause clinical hypothyroidism. Monitoring of serum concentrations of T3 and dose adjustment of tiratricol may be necessary during and after treatment with antimalarial medicinal products.
Anabolic steroids and glucocorticoids are known to decrease serum Thyroxine-Binding Globulin (TBG) concentration and may result in lower T3 and tiratricol serum concentration.
Salicylates, anti-coagulants, anti-inflammatory and anti-convulsant medicinal products may cause protein binding site displacement of T3, and potentially tiratricol, from (TBG) and thereby altering serum levels of thyroid hormones, i.e. lower total concentrations but free concentrations remain the same.
Non-contraceptive oestrogen and oestrogen containing products (including hormone replacement therapy) may increase the requirement of tiratricol treatment dose.
Orlistat may decrease tiratricol absorption which may result in hypothyroidism (changes in thyroid function should be monitored).
Based on in vitro data there is an indication that tiratricol may induce CYP3A4 at a gut level and therefore medicinal products with narrow therapeutic indices that are dependent on CYP3A4, including but not limited to: alfentanil, cisapride, cyclosporine, ergot derivatives, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, atorvastatin, lovastatin, and simvastatin should be used with caution. Similar precautions should be applied to other agents that are known to depend on CYP3A4 for metabolism. Medicinal products that are substrates of P-glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP) efflux transporters with narrow therapeutic indices should also be used with caution.
Taking tiratricol in combination with other thyromimetic medicinal products or other medicinal products used to treat thyroid conditions (e.g. levothyroxine, propylthiouracil, and carbimazole) may increase the risk of symptoms of hyperthyroidism or hypothyroidism.
Administration of psychostimulants (e.g. caffeine, norepinephrine–dopamine reuptake inhibitors (NDRIs), and amphetamines) in combination with high doses of tiratricol may lead to increased heart rate and blood pressure. Concomitant use of psychostimulants and tiratricol is not recommended.
Tiratricol may reduce blood glucose levels. The dose of anti-diabetic agents may need to be adjusted if administered concomitantly with tiratricol. Periodic monitoring of blood glucose is necessary (see section 4.4).
The effect of anti-coagulant therapy may be increased during treatment with tiratricol. This may increase the risk of haemorrhage. The dose of anti-coagulant therapy may have to be adjusted if administered concomitantly with tiratricol.
MCT8 deficiency is an X-linked disease that almost exclusively affects males.
Tiratricol crosses the placenta. There are no or limited amount of data from the use of tiratricol in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Emcitate is contraindicated during pregnancy (see section 4.3).
Women of childbearing potential have to use effective contraception during treatment.
It is unknown whether tiratricol/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Emcitate therapy considering the benefit of breast-feeding for the child and the benefit of therapy for the woman.
A study in rats showed no impact on fertility and mating ability (see section 5.3).
Emcitate has no or negligible influence on the ability to drive and use machines.
The most commonly reported adverse reactions associated with the use of tiratricol treatment were hyperhidrosis (7%), diarrhoea (6%), irritability (2%), anxiety (2%), and nightmares (2%). These reactions usually occurred at the start of treatment and/or when the dose was increased, and generally resolved within a few days.
The safety assessment of tiratricol is based on data from clinical trials. Adverse reactions are listed by MedDRA system organ class and frequency convention as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data).
Table 3. Adverse reactions:
| System organ class | Adverse reaction | Frequency category |
|---|---|---|
| Psychiatric disorders | Irritability Anxiety Nightmares Insomnia | Common Common Common Not known |
| Cardiac disorders | Tachycardia | Not known |
| Gastrointestinal disorders | Diarrhoea | Common |
| Skin and subcutaneous tissue disorders | Hyperhidrosis | Common |
| General disorders and administration site conditions | Hyperthermia | Not known |
In clinical trials in patients with MCT8 deficiency, the onset of the observed adverse reactions hyperhidrosis, irritability, anxiety, and nightmares coincided with treatment initiation or dose modification. In all cases, these reactions were mild and resolved spontaneously.
At initiation of tiratricol treatment and/or during dose titration, new onset or worsening of hypermetabolic signs and symptoms, such as hyperhidrosis, irritability, anxiety, insomnia, nightmares, hyperthermia, tachycardia, transient elevations in systolic blood pressure (SBP), or diarrhoea, may occur (see section 4.4).
Safety data were evaluated in 63 patients between 0 and 17 years of age, in Triac Trial I and Triac Trial II combined. Thirty (30) patients were below 2 years of age at start of treatment, 25 patients were between 2 and 11 years of age and 8 patients were between 12 and 17 years of age. There is no indication from clinical trial data that the safety profile in any subset of the paediatric population is different from the safety profile in adult patients.
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 national reporting system listed in Appendix V.
Not applicable.
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