Dosing

SmPC Contraindications, special warnings, precautions for use and medicinal interactions:

• Contraindicationsexpand_more
  • Hypersensitivity to active substance or to any of the excipients.
• Information about excipientsexpand_more
  • Sodium - This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free’.
• Precautions for Use, inc. pregnancy, lactation and fertilityexpand_more
  • Pregnancy
    : There are no data on the use of acoramidis in pregnant women. Studies in animals have shown developmental toxicity at a dose which also caused maternal toxicity. Acoramidis is not recommended during pregnancy and in women of childbearing potential not using contraception.
  • Lactation
    : It is unknown whether acoramidis or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Acoramidis should not be used during breast feeding.
  • Fertility
    : No human data on fertility is available. Impairment of fertility has not been observed in non-clinical studies in supratherapeutic exposures.
• Special Warningsexpand_more
  • Hepatic impairment
    : Beyonttra has not been studied in patients with hepatic impairment and therefore is not recommended for use in this population.
  • Renal impairment
    : Based on low renal clearance of Beyonttra, no dose adjustment is required. Data in patients with severe renal impairment (creatinine clearance <30 mL/min) are limited. There are no data for patients on dialysis hence acoramidis should be used with caution in this population.
  • Renal Haemodynamic parameters:
    • Patients treated with Beyonttra experienced an initial drop in eGFR in the first month of treatment and a corresponding increase in measured serum creatinine.
    • This change in eGFR and creatinine was non-progressive, reversible in those patients whose treatment was interrupted, and not associated with kidney injury, consistent with a haemodynamic effect.
• Interactions with other medicinal products and other forms of interactionsexpand_more

  Effect of Acoramidis on other medicinal products:

  • Based on a clinical study in healthy adult volunteers, inhibition of organic anion transporter (OAT)-1 and -3 is not expected to result in clinically relevant drug-drug interactions with OAT-1 and OAT-3 substrates (e.g., non-steroidal anti-inflammatory medicines, bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, zalcitabine).
  • Based on an in vitro study, no drug-drug interaction with co-administered breast cancer resistance protein (BCRP) substrates is anticipated at clinically relevant concentrations.  
  • Based on in vitro studies, acoramidis is unlikely to cause any clinically relevant uridine 5'-diphospho (UDP)-glucuronosyl transferase-dependent or Cytochrome P450-dependent interactions. However, acoramidis was shown to be an inhibitor of CYP2C8 and CYP2C9 in vitro. No in vivo study has been performed. Therefore, concomitant CYP2C8 and CYP2C9 substrates with narrow therapeutic index should be used with caution.

  Effect of other medicinal products on acoramidis:

  Diuretics:

  • Based on population pharmacokinetic (PK) analysis, concomitant diuretic use in patients does not affect steady-state plasma acoramidis concentrations.

  Breast Cancer Resistance Protein (BCRP) inhibitors:

  • Acoramidis is a substrate for BCRP. Based on an in vitro study, a clinically relevant interaction with BCRP inhibitors is not expected.

  Gastric acid reducing agents:

  • No dedicated in vivo drug-drug interaction study with gastric acid reducing agents was performed. Thus, the effect of gastric acid reducing agents on the pharmacokinetics of acoramidis is unknown. Despite the marked pH dependent solubility of acoramidis in the physiological pH range, no differences were observed in the systemic exposure to acoramidis or in the pharmacodynamic marker (TTR stabilisation) between patients taking acid reducing agents and patients not taking acid reducing agents, in the phase 3 study.

  Effect on laboratory test:

  • Acoramidis may decrease serum concentrations of free thyroxine without an accompanying change in thyroid stimulating hormone (TSH). No corresponding clinical findings consistent with thyroid dysfunction have been observed.