Vyndaqel

/ Pfizer

Treatment should be initiated under the supervision of a physician knowledgeable in the management of patients with transthyretin amyloid polyneuropathy (ATTR-PN).
The recommended dose of tafamidis meglumine is 20 mg orally once daily.
Tafamidis and tafamidis meglumine are not interchangeable on a per mg basis. If vomiting occurs after dosing, and the intact capsule is identified, then an additional dose of the drug should be administered if possible. If no capsule is identified, then no additional dose is necessary, with resumption of dosing the next day as usual.
Elderly
No dosage adjustment is required for elderly patients (≥ 65 years).
Hepatic and renal impairment
No dosage adjustment is required for patients with renal or mild and moderate hepatic impairment.
Limited data are available in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min). Tafamidis meglumine has not been studied in patients with severe hepatic impairment and caution is recommended.
Pediatric population
There is no relevant use of tafamidis in the pediatric population.
The soft capsules should be swallowed whole not crushed or cut taken with or without food.

Treatment of transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment.

Hypersensitivity to the active substance or to any of the excipients.

Women of childbearing potential should use appropriate contraception when taking tafamidis meglumine and continue to use appropriate contraception for 1-month after stopping treatment with tafamidis meglumine.
Tafamidis meglumine should be added to the standard of care for the treatment of patients with ATTR-PN . Physicians should monitor patients and continue to assess the need for other therapy, including the need for liver transplantation, as part of this standard of care. As there are no data available regarding the use of tafamidis meglumine post-liver transplantation, this drug  should be discontinued in patients who undergo liver transplantation.
This medicinal product contains no more than 44 mg sorbitol in each capsule. Sorbitol is a source of fructose.
The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.

Very common: Urinary tract infection, vaginal infection, diarrhoea, upper abdominal pain.
See prescribing information for full details.

In a clinical study in healthy volunteers, 20 mg tafamidis meglumine did not induce or inhibit the cytochrome P450 enzyme CYP3A4 .
In vitro Tafamidis inhibits the efflux transporter BCRP (breast cancer resistant protein) with IC50=1.16 μM and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter (e.g. methotrexate, rosuvastatin, imatinib) following a 20 mg tafamidis meglumine dose. Likewise, tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) with IC50=2.9 μM and IC50=2.36 μM, respectively, and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters (e.g. non-steroidal anti-inflammatory drugs, bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, zalcitabine).
Based on in vitro data, the maximal predicted changes in AUC of OAT1 and OAT3 substrates were determined to be less than 1.25 for the tafamidis meglumine 20 mg dose, therefore, inhibition of OAT1 or OAT3 transporters by tafamidis is not expected to result in clinically significant interactions.
No interaction studies have been performed evaluating the effect of other medicinal products on tafamidis meglumine.

Pregnancy
There are no data on the use of tafamidis megluminein pregnant women. See prescribing information for full details.
Lactation: Tafamidis meglumine should not be used during breast-feeding. See prescribing information for full details.

There is minimal clinical experience with overdose. During clinical trials, two patients diagnosed with transthyretin amyloid cardiomyopathy (ATTR-CM) accidentally ingested a single tafamidis meglumine dose of 160 mg without the occurrence of any associated adverse events. The highest dose of tafamidis meglumine given to healthy volunteers in a clinical trial was 480 mg as a single dose . There was one reported treatment-related adverse event of mild hordeolum at this dose Management
In case of overdose, standard supportive measures should be instituted as required.

Laboratory test abnormality
Tafamidis may decrease serum concentrations of total thyroxine, without an accompanying change in free thyroxine (T4) or thyroid stimulating hormone (TSH). This observation in total thyroxine values may likely be the result of reduced thyroxine binding to or displacement from transthyretin (TTR) due to the high binding affinity tafamidis has to the TTR thyroxine receptor. No corresponding clinical findings consistent with thyroid dysfunction have been observed.