Chemical formula: C₁₄H₉I₃O₄ Molecular mass: 621.932 g/mol PubChem compound: 5803
Tiratricol interacts in the following cases:
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.
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.
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.
No specific studies have been performed in patients with hepatic impairment. In these patients, careful dose titration and regular monitoring of serum concentrations of T3 are recommended.
No specific studies have been performed in patients with renal impairment. In these patients, careful dose titration and regular monitoring of serum concentrations of T3 are recommended.
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.
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.
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.
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.
Orlistat may decrease tiratricol absorption which may result in hypothyroidism (changes in thyroid function should be monitored).
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.
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.
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.
Caution should be used in patients with diabetes.
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.
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. Tiratricol is contraindicated during pregnancy.
MCT8 deficiency is an X-linked disease that almost exclusively affects males.
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 tiratricol therapy considering the benefit of breast-feeding for the child and the benefit of therapy for the woman.
MCT8 deficiency is an X-linked disease that almost exclusively affects males.
Women of childbearing potential have to use effective contraception during treatment.
A study in rats showed no impact on fertility and mating ability.
Tiratricol 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).
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.
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.
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