Vyndaqel

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Health care professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 20 mg soft capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each soft capsule contains 20 mg of micronized tafamidis meglumine equivalent to 12.2 mg tafamidis.

Excipient with known effect

Each soft capsule contains no more than 44 mg of sorbitol (E 420).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Soft capsule.

Yellow, opaque, oblong (approximately 21 mm) capsule imprinted with “VYN 20” in red.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Vyndaqel is indicated for the treatment of transthyretin amyloidosis in adult patients with stage 1 
symptomatic polyneuropathy to delay peripheral neurologic impairment.

4.2 Posology and method of administration

Treatment should be initiated under the supervision of a physician knowledgeable in the management 
of patients with transthyretin amyloid polyneuropathy (ATTR-PN).

Posology

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 Vyndaqel capsule is identified, then an additional dose 
of Vyndaqel 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.

Special populations

Elderly

No dosage adjustment is required for elderly patients (≥ 65 years) (see section 5.2).



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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 (see section 5.2).

Paediatric population

There is no relevant use of tafamidis in the paediatric population. 

Method of administration

Oral use.

The soft capsules should be swallowed whole and not crushed or cut. Vyndaqel may be taken with or 
without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use 

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 (see section 4.6).

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, tafamidis meglumine 
should be discontinued in patients who undergo liver transplantation.

This medicinal product contains no more than 44 mg sorbitol in each capsule.

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.

4.5 Interaction with other medicinal products and other forms of interaction 

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 



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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.

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.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

Contraceptive measures should be used by women of childbearing potential during treatment with 
tafamidis meglumine, and for one month after stopping treatment, due to the prolonged half-life.

Pregnancy

There are no data on the use of tafamidis meglumine in pregnant women. Studies in animals have 
shown developmental toxicity (see section 5.3). Tafamidis meglumine is not recommended during 
pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

Available data in animals have shown excretion of tafamidis in milk. A risk to the newborns/infants 
cannot be excluded. Tafamidis meglumine should not be used during breast-feeding.

Fertility

No impairment of fertility has been observed in nonclinical studies (see section 5.3).

4.7 Effects on ability to drive and use machines

On the basis of the pharmacodynamic and pharmacokinetic profile, tafamidis meglumine is believed to 
have no or negligible influence on the ability to drive or use machines.

4.8 Undesirable effects

Summary of the safety profile

The overall clinical data reflect exposure of 127 patients with ATTR-PN to 20 mg of tafamidis 
meglumine administered daily for an average of 538 days (ranging from 15 to 994 days). The adverse 
reactions were generally mild or moderate in severity.

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA System Organ Class (SOC) and frequency categories 
using the standard convention: Very common ( 1/10), Common ( 1/100 to < 1/10), and Uncommon 
( 1/1,000 to < 1/100). Within the frequency group, adverse reactions are presented in order of 
decreasing seriousness. Adverse reactions reported from the clinical programme in the tabular listing 
below reflect the rates at which they occurred in the Phase 3, double-blind, placebo-controlled study 
(Fx-005).



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System Organ Class Very Common
Infections and infestations Urinary tract infection

Vaginal infection
Gastrointestinal disorders Diarrhoea

Upper abdominal pain

Reporting of suspected adverse reactions

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.

4.9 Overdose

Symptoms

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.

5. PHARMACOLOGIC PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other nervous system drugs, ATC code N07XX08

Mechanism of action

Tafamidis is a selective stabiliser of TTR. Tafamidis binds to TTR at the thyroxine binding sites, 
stabilising the tetramer and slowing dissociation into monomers, the rate-limiting step in the 
amyloidogenic process.

Pharmacodynamic effects

Transthyretin amyloidosis is a severely debilitating condition induced by the accumulation of various 
insoluble fibrillar proteins, or amyloid, within the tissues in amounts sufficient to impair normal 
function. The dissociation of the transthyretin tetramer to monomers is the rate-limiting step in the 
pathogenesis of transthyretin amyloidosis. The folded monomers undergo partial denaturation to 
produce alternatively folded monomeric amyloidogenic intermediates. These intermediates then 
misassemble into soluble oligomers, profilaments, filaments, and amyloid fibrils. Tafamidis binds with 
negative cooperativity to the two thyroxine binding sites on the native tetrameric form of transthyretin 
preventing dissociation into monomers. The inhibition of TTR tetramer dissociation forms the 
rationale for the use of tafamidis to slow disease progression in stage 1 ATTR-PN patients.

A TTR stabilisation assay was utilised as a pharmacodynamic marker and assessed the stability of the 
TTR tetramer. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Tafamidis stabilised both the wild-type TTR tetramer and the tetramers of 14 TTR variants tested 
clinically after once-daily dosing with tafamidis. Tafamidis also stabilised the TTR tetramer for 
25 variants tested ex vivo, thus demonstrating TTR stabilisation of 40 amyloidogenic TTR genotypes.

Clinical efficacy and safety 

The pivotal study of tafamidis meglumine in stage 1 ATTR-PN patients was an 18-month, multicentre, 
randomised, double-blind, placebo-controlled study. The study evaluated the safety and efficacy of 
once-daily 20 mg tafamidis meglumine in 128 patients with ATTR-PN with the V30M mutation and 
primarily stage 1 disease; 126 of the 128 patients did not routinely require assistance with ambulation. 
The primary outcome measures were the Neuropathy Impairment Score of the Lower Limb (NIS-LL –
a physician assessment of the neurologic exam of the lower limbs) and the Norfolk Quality of Life -
Diabetic Neuropathy (Norfolk QOL-DN – a patient reported outcome, total quality of life score 
[TQOL]). Other outcome measures included composite scores of large nerve fibre (nerve conduction, 
vibration threshold and heart rate response to deep breathing - HRDB) and small nerve fibre function 
(heat pain and cooling threshold and HRDB) and nutritional assessments utilizing the modified body 
mass index (mBMI – BMI multiplied by serum albumin in g/L). Eighty-six of the 91 patients 
completing the 18 month treatment period subsequently enrolled in an open-label extension study, 
where they all received once daily 20 mg tafamidis meglumine for an additional 12 months.

Following 18 months of treatment, more tafamidis meglumine-treated patients were NIS-LL 
Responders (change of less than 2 points on NIS-LL) Outcomes for the pre-specified analyses of the 
primary endpoints are provided in the following table:

Vyndaqel versus Placebo: NIS-LL and TQOL at Month 18 (Study Fx-005)
Placebo Vyndaqel

Pre-specified ITT Analysis N=61 N=64
NIS-LL Responders (% Patients) 29.5% 45.3%

Difference (Vyndaqel minus Placebo)
95% CI of Difference (p-value)

15.8%
-0.9%, 32.5% (0.068)

TQOL Change from Baseline LSMean (SE) 7.2 (2.36) 2.0 (2.31)
Difference in LSMeans (SE)
95% CI of Difference (p-value)

-5.2 (3.31)
-11.8, 1.3 (0.116)

Pre-specified Efficacy Evaluable Analysis N=42 N=45
NIS-LL Responders (% Patients) 38.1% 60.0%

Difference (Vyndaqel minus Placebo)
95% CI of Difference (p-value)

21.9%
1.4%, 42.4% (0.041)

TQOL Change from Baseline LSMean (SE) 8.9 (3.08) 0.1 (2.98)
Difference in LSMeans (SE)
95% CI of Difference (p-value)

-8.8 (4.32)
-17.4, -0.2 (0.045)

In the pre-specified ITT NIS-LL Responder analysis, patients who discontinued prior to the 18-month time point due to liver 
transplantation were categorized as non-responders. The pre-specified Efficacy Evaluable analysis used observed data for those patients 
who completed the 18 month treatment per protocol.

The secondary endpoints demonstrated that tafamidis meglumine treatment resulted in less 
deterioration of neurologic function and improved nutritional status (mBMI) compared with placebo, 
as shown in the following table. 

Secondary Endpoints Changes from Baseline to Month 18 LSMean (Standard Error) 
(Intent-to-Treat Population) (Study Fx-005)

Placebo
N=61

Vyndaqel
N=64

P-value Vyndaqel % change 
relative to Placebo

NIS-LL change from BL
LSMean (SE)

5.8 (0.96) 2.8 (0.95) 0.027 -52%

Large Fibre change from BL
LSMean (SE)

3.2 (0.63) 1.5 (0.62) 0.066 -53%



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Secondary Endpoints Changes from Baseline to Month 18 LSMean (Standard Error) 
(Intent-to-Treat Population) (Study Fx-005)

Placebo
N=61

Vyndaqel
N=64

P-value Vyndaqel % change 
relative to Placebo

Small Fibre change from BL
LSMean (SE)

1.6 (0.32) 0.3 (0.31) 0.005 -81%

mBMI change from BL
LSMean (SE)

-33.8 
(11.8)

39.3 (11.5) < 0.0001 NA

mBMI was derived as the product of serum albumin and Body Mass Index.
Based on repeated measures analysis of variance with change from baseline as the dependent variable, an unstructured covariance matrix, 
treatment, month and treatment-by-month as fixed effects, and subject as a random effect in the model.
NA=not applicable.

In the open-label extension study, the rate of change in the NIS-LL during the 12 months of treatment 
was similar to that observed in those patients randomised and treated with tafamidis in the previous 
double blind 18 month period.

Although data are limited, (one open-label study in 21 patients), taking into account the mechanism of 
action of tafamidis and the results on TTR stabilisation, tafamidis meglumine is expected to be 
beneficial in patients with stage 1 ATTR-PN due to mutations other than V30M.

The effects of tafamidis have been assessed in a double-blind, placebo-controlled, randomised 3-arm 
study in 441 patients with wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM).
The primary analysis of pooled tafamidis meglumine (20 mg and 80 mg) versus placebo demonstrated 
a significant reduction (p=0.0006) in all-cause mortality and frequency of cardiovascular-related 
hospitalisations.

A supra-therapeutic, single, 400 mg oral dose of tafamidis solution in healthy volunteers demonstrated 
no prolongation of the QTc interval.

The European Medicines Agency has waived the obligation to submit the results of studies with 
tafamidis in all subsets of the paediatric population in transthyretin amyloidosis (see section 4.2 for 
information on paediatric use).

This medicinal product has been authorised under ‘exceptional circumstances’. This means that due to 
the rarity of the disease it has not been possible to obtain complete information on this medicinal 
product. The European Medicines Agency will review any new information which may become 
available every year and this SmPC will be updated as necessary.

5.2 Pharmacokinetic properties 

Absorption

After oral administration of the soft capsule once daily, the maximum peak concentration (Cmax) is 
achieved within a median time (tmax) of 4 hours after dosing in the fasted state. Concomitant 
administration of a high fat, high calorie meal altered the rate of absorption, but not the extent of 
absorption. These results support the administration of tafamidis with or without food.

Distribution

Tafamidis is highly protein bound (> 99%) in plasma. The apparent steady-state volume of distribution 
is 16 litres. 

The extent of tafamidis binding to plasma proteins has been evaluated using animal and human 
plasma. The affinity of tafamidis for TTR is greater than that for albumin. Therefore, in plasma, 
tafamidis is likely to bind preferentially to TTR despite the significantly higher concentration of 
albumin (600 μM) relative to TTR (3.6 μM).



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Biotransformation and elimination

There is no explicit evidence of biliary excretion of tafamidis in humans. Based on preclinical data, it 
is suggested that tafamidis is metabolised by glucuronidation and excreted via the bile. This route of 
biotransformation is plausible in humans, as approximately 59% of the total administered dose is 
recovered in faeces, and approximately 22% recovered in urine. Based on population pharmacokinetic 
results, the apparent oral clearance of tafamidis meglumine is 0.228 L/h and the population mean 
half-life is approximately 49 hours.

Dose and time linearity

Exposure from once-daily dosing with tafamidis meglumine increased with increasing dose up to 
480 mg single dose and multiple doses up to 80 mg/day. In general, increases were proportional or 
near proportional to dose and tafamidis clearance was stationary over time.

Pharmacokinetic parameters were similar after single and repeated administration of 20 mg tafamidis 
meglumine, indicating a lack of induction or inhibition of tafamidis metabolism.

Results of once-daily dosing with 15 mg to 60 mg oral solution tafamidis meglumine for 14 days 
demonstrated that steady-state was achieved by Day 14. 

Special populations

Hepatic impairment

Pharmacokinetic data indicated decreased systemic exposure (approximately 40%) and increased total 
clearance (0.52 L/h versus 0.31 L/h) of tafamidis meglumine in patients with moderate hepatic 
impairment (Child-Pugh Score of 7-9 inclusive) compared to healthy subjects due to a higher unbound 
fraction of tafamidis. As patients with moderate hepatic impairment have lower TTR levels than 
healthy subjects, dosage adjustment is not necessary as the stoichiometry of tafamidis with its target 
protein TTR would be sufficient for stabilisation of the TTR tetramer. The exposure to tafamidis in 
patients with severe hepatic impairment is unknown.

Renal impairment

Tafamidis has not specifically been evaluated in a dedicated study of patients with renal impairment. 
The influence of creatinine clearance on tafamidis pharmacokinetics was evaluated in a population 
pharmacokinetic analysis in patients with creatinine clearance greater than 18 mL/min. 
Pharmacokinetic estimates indicated no difference in apparent oral clearance of tafamidis in patients 
with creatinine clearance less than 80 mL/min compared to those with creatinine clearance greater than 
or equal to 80 mL/min. Dosage adjustment in patients with renal impairment is considered not 
necessary.

Elderly

Based on population pharmacokinetic results, subjects ≥ 65 years had an average 15% lower estimate 
of apparent oral clearance at steady-state compared to subjects less than 65 years old. However, the 
difference in clearance results in < 20% increases in mean Cmax and AUC compared to younger 
subjects and is not clinically significant.

Pharmacokinetic/pharmacodynamic relationships

In vitro data indicated that tafamidis does not significantly inhibit cytochrome P450 enzymes 
CYP1A2, CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. Tafamidis is 
not expected to cause clinically relevant drug interaction due to induction of CYP1A2, CYP2B6 or 
CYP3A4.



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In vitro studies suggest that it is unlikely tafamidis will cause drug interactions at clinically relevant 
concentrations with substrates of UDP glucuronosyltransferase (UGT) systemically. Tafamidis may 
inhibit intestinal activities of UGT1A1.

Tafamidis showed a low potential to inhibit Multi-Drug Resistant Protein (MDR1) (also known as 
P-glycoprotein; P-gp) systemically and in the gastrointestinal (GI) tract, organic cation transporter 2 
(OCT2), multidrug and toxin extrusion transporter 1 (MATE1) and MATE2K, organic anion 
transporting polypeptide 1B1 (OATP1B1) and OATP1B3 at clinically relevant concentrations.

5.3 Preclinical safety data 

Nonclinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, fertility and early embryonic development, genotoxicity and carcinogenic potential. In 
repeat-dose toxicity and the carcinogenicity studies, the liver appeared as a target organ for toxicity in 
the different species tested. Liver effects were seen at exposures approximately ≥ 2.5-times the human 
AUC at steady-state at the clinical dose of 20 mg tafamidis meglumine.

In a developmental toxicity study in rabbits, a slight increase in skeletal malformations and variations, 
abortions in few females, reduced embryo-foetal survival, and reduction in foetal weights were 
observed at exposures approximately ≥ 7.2 times the human AUC at steady-state at the clinical dose of 
20 mg tafamidis meglumine.

In the rat pre- and postnatal development study with tafamidis, decreased pup survival and reduced 
pup weights were noted following maternal dose administration during pregnancy and lactation at 
doses of 15 and 30 mg/kg/day. Decreased pup weights in males were associated with delayed sexual 
maturation (preputial separation) at 15 mg/kg/day. Impaired performance in a water-maze test for 
learning and memory was observed at 15 mg/kg/day. The NOAEL for viability and growth in the F1 
generation offspring following maternal dose administration during pregnancy and lactation with 
tafamidis was 5 mg/kg/day (human equivalent dose = 0.8 mg/kg/day), a dose approximately 4.6 times 
the clinical dose of 20 mg tafamidis meglumine.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule shell 

Gelatine (E 441)
Glycerine (E 422)
Yellow iron oxide (E 172)
Sorbitan
Sorbitol (E 420)
Mannitol (E 421)
Titanium dioxide (E 171)
Purified water

Capsule contents 

Macrogol 400 (E 1521)
Sorbitan monooleate (E 494)
Polysorbate 80 (E 433)

Printing ink (Opacode purple)

Ethyl alcohol
Isopropyl alcohol



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Purified water
Macrogol 400 (E 1521)
Polyvinyl acetate phthalate
Propylene glycol (E 1520)
Carmine (E 120)
Brilliant Blue FCF (E 133)
Ammonium hydroxide (E 527) 28%

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

PVC/PA/alu/PVC-alu/PET/Paper perforated unit dose blisters.

Pack sizes: a pack of 30 x 1 soft capsules and a multipack containing 90 (3 packs of 30 x 1) soft 
capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/001
EU/1/11/717/002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 16 November 2011
Date of latest renewal: 22 July 2016



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10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu.

http://www.ema.europa.eu/


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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 61 mg soft capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each soft capsule contains 61 mg of micronized tafamidis.

Excipient with known effect

Each soft capsule contains no more than 44 mg of sorbitol (E 420).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Soft capsule.

Reddish brown, opaque, oblong (approximately 21 mm) capsule printed with “VYN 61” in white.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Vyndaqel is indicated for the treatment of wild-type or hereditary transthyretin amyloidosis in adult 
patients with cardiomyopathy (ATTR-CM).

4.2 Posology and method of administration

Treatment should be initiated under the supervision of a physician knowledgeable in the management 
of patients with amyloidosis or cardiomyopathy.

When there is a suspicion in patients presenting with specific medical history or signs of heart failure 
or cardiomyopathy, etiologic diagnosis must be done by a physician knowledgeable in the 
management of amyloidosis or cardiomyopathy to confirm ATTR-CM and exclude AL amyloidosis 
before starting tafamidis, using appropriate assessment tools such as: bone scintigraphy and 
blood/urine assessment, and/or histological assessment by biopsy, and transthyretin (TTR) genotyping 
to characterise as wild-type or hereditary.

Posology

The recommended dose is one capsule of Vyndaqel 61 mg (tafamidis) orally once daily (see section 
5.1).

Vyndaqel 61 mg (tafamidis) corresponds to 80 mg tafamidis meglumine. Tafamidis and tafamidis 
meglumine are not interchangeable on a per mg basis (see section 5.2).

Vyndaqel should be started as early as possible in the disease course when the clinical benefit on 
disease progression could be more evident. Conversely, when amyloid-related cardiac damage is more 
advanced, such as in NYHA Class III, the decision to start or maintain treatment should be taken at the 



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discretion of a physician knowledgeable in the management of patients with amyloidosis or 
cardiomyopathy (see section 5.1). There are limited clinical data in patients with NYHA Class IV.

If vomiting occurs after dosing, and the intact Vyndaqel capsule is identified, then an additional dose 
of Vyndaqel 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.

Special populations

Elderly

No dosage adjustment is required for elderly patients (≥ 65 years) (see section 5.2).

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 has not been studied in patients with severe hepatic impairment and 
caution is recommended (see section 5.2).

Paediatric population

There is no relevant use of tafamidis in the paediatric population.

Method of administration

Oral use.

The soft capsules should be swallowed whole and not crushed or cut. Vyndaqel may be taken with or 
without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use 

Women of childbearing potential should use appropriate contraception when taking tafamidis and 
continue to use appropriate contraception for 1-month after stopping treatment with tafamidis (see 
section 4.6).

Tafamidis should be added to the standard of care for the treatment of patients with transthyretin 
amyloidosis. Physicians should monitor patients and continue to assess the need for other therapy, 
including the need for organ transplantation, as part of this standard of care. As there are no data 
available regarding the use of tafamidis in organ transplantation, tafamidis should be discontinued in 
patients who undergo organ transplantation.

Increase in liver function tests and decrease in thyroxine may occur (see section 4.5 and 4.8).

This medicinal product contains no more than 44 mg sorbitol in each capsule.

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.



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4.5 Interaction with other medicinal products and other forms of interaction 

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) at the 
61 mg/day tafamidis dose 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 61 mg/day tafamidis 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 61 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.

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 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.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

Contraceptive measures should be used by women of childbearing potential during treatment with 
tafamidis, and for one month after stopping treatment, due to the prolonged half-life.

Pregnancy

There are no data on the use of tafamidis in pregnant women. Studies in animals have shown 
developmental toxicity (see section 5.3). Tafamidis is not recommended during pregnancy and in 
women of childbearing potential not using contraception.

Breast-feeding

Available data in animals have shown excretion of tafamidis in milk. A risk to the newborns/infants 
cannot be excluded. Tafamidis should not be used during breast-feeding.

Fertility

No impairment of fertility has been observed in nonclinical studies (see section 5.3).

4.7 Effects on ability to drive and use machines

On the basis of the pharmacodynamic and pharmacokinetic profile, tafamidis is believed to have no or 
negligible influence on the ability to drive or use machines.



15

4.8 Undesirable effects

Summary of the safety profile

The safety data reflect exposure of 176 patients with ATTR-CM to 80 mg (administered as 4 x 20 mg) 
of tafamidis meglumine administered daily in a 30-month placebo-controlled trial in patients 
diagnosed with ATTR-CM (see section 5.1). 

The frequency of adverse events in patients treated with 80 mg tafamidis meglumine was generally
similar and comparable to placebo.

The following adverse events were reported more often in patients treated with tafamidis meglumine 
80 mg compared to placebo: flatulence [8 patients (4.5%) versus 3 patients (1.7%)] and liver function 
test increased [6 patients (3.4%) versus 2 patients (1.1%)]. A causal relationship has not been 
established.

Safety data for tafamidis 61 mg are not available as this formulation was not evaluated in the 
double-blind, placebo-controlled, randomised phase 3 study.

Reporting of suspected adverse reactions

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.

4.9 Overdose

Symptoms

There is minimal clinical experience with overdose. During clinical trials, two patients diagnosed with 
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.

5. PHARMACOLOGIC PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other nervous system drugs, ATC code: N07XX08

Mechanism of action

Tafamidis is a selective stabiliser of TTR. Tafamidis binds to TTR at the thyroxine binding sites, 
stabilising the tetramer and slowing dissociation into monomers, the rate-limiting step in the 
amyloidogenic process.

Pharmacodynamic effects

Transthyretin amyloidosis is a severely debilitating condition induced by the accumulation of various 
insoluble fibrillar proteins, or amyloid, within the tissues in amounts sufficient to impair normal 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


16

function. The dissociation of the transthyretin tetramer to monomers is the rate-limiting step in the 
pathogenesis of transthyretin amyloidosis. The folded monomers undergo partial denaturation to 
produce alternatively folded monomeric amyloidogenic intermediates. These intermediates then 
misassemble into soluble oligomers, profilaments, filaments, and amyloid fibrils. Tafamidis binds with 
negative cooperativity to the two thyroxine binding sites on the native tetrameric form of transthyretin 
preventing dissociation into monomers. The inhibition of TTR tetramer dissociation forms the 
rationale for the use of tafamidis in ATTR-CM patients.

A TTR stabilisation assay was utilised as a pharmacodynamic marker, and assessed the stability of the 
TTR tetramer. 

Tafamidis stabilised both the wild-type TTR tetramer and the tetramers of 14 TTR variants tested 
clinically after once-daily dosing with tafamidis. Tafamidis also stabilised the TTR tetramer for 
25 variants tested ex vivo, thus demonstrating TTR stabilisation of 40 amyloidogenic TTR genotypes. 

In a multicentre, international, double-blind, placebo-controlled, randomised study (see Clinical 
efficacy and safety section), TTR stabilisation was observed at Month 1 and was maintained through 
Month 30. 

Biomarkers associated with heart failure (NT-proBNP and Troponin I) favoured Vyndaqel over 
placebo. 

Clinical efficacy and safety 

Efficacy was demonstrated in a multicentre, international, double-blind, placebo-controlled, 
randomised 3-arm study in 441 patients with wild-type or hereditary ATTR-CM. 

Patients were randomised to either tafamidis meglumine 20 mg (n=88) or 80 mg [administered as 
four 20 mg tafamidis meglumine capsules] (n=176) or matching placebo (n=177) once daily, in 
addition to standard of care (e.g. diuretics) for 30 months. Treatment assignment was stratified by the 
presence or absence of a variant TTR genotype as well as by baseline severity of disease (NYHA 
Class). Table 1 describes the patient demographics and baseline characteristics.

Table 1: Patient demographics and baseline characteristics

Characteristic Pooled Tafamidis
N=264

Placebo
N=177

Age — year
Mean (standard deviation) 74.5 (7.2) 74.1 (6.7)
Median (minimum, maximum) 75 (46, 88) 74 (51, 89)

Sex — number (%)
Male 241 (91.3) 157 (88.7)
Female 23 (8.7) 20 (11.3)

TTR genotype — number (%)
ATTRm 63 (23.9) 43 (24.3)
ATTRwt 201 (76.1) 134 (75.7)

NYHA Class — number (%)
NYHA Class I 24 (9.1) 13 (7.3)
NYHA Class II 162 (61.4) 101 (57.1)
NYHA Class III 78 (29.5) 63 (35.6)

Abbreviations: ATTRm=variant transthyretin amyloid, ATTRwt=wild-type transthyretin amyloid, NYHA=New York Heart Association.

The primary analysis used a hierarchical combination applying the method of Finkelstein-Schoenfeld 
(F-S) to all-cause mortality and frequency of cardiovascular-related hospitalisations, which is defined 
as the number of times a subject is hospitalised (i.e., admitted to a hospital) for cardiovascular-related 
morbidity. The method compared each patient to every other patient within each stratum in a pair-wise 



17

manner that proceeds in a hierarchical fashion using all-cause mortality followed by frequency of 
cardiovascular-related hospitalisations when patients cannot be differentiated based on mortality. 

This analysis demonstrated a significant reduction (p=0.0006) in all-cause mortality and frequency of 
cardiovascular-related hospitalisations in the pooled tafamidis 20 mg and 80 mg dose group versus 
placebo (Table 2). 

Table 2: Primary analysis using Finkelstein-Schoenfeld (F-S) Method of all-cause mortality and 
frequency of cardiovascular-related hospitalisations

Primary analysis Pooled Tafamidis
N=264

Placebo
N=177

Number (%) of subjects alive* at month 30 186 (70.5) 101 (57.1)
Average cardiovascular-related hospitalisations during 
30 months (per patient per year) among those alive at 
month 30†

0.297 0.455

p-value from F-S Method 0.0006
* Heart transplantation and cardiac mechanical assist device implantation are considered indicators of approaching end stage. As such, these 
subjects are treated in the analysis as equivalent to death. Therefore, such subjects are not included in the count of “Number of Subjects Alive 
at Month 30” even if such subjects are alive based on 30 month vital status follow-up assessment. 
† Descriptive mean among those who survived the 30 months.

Analysis of the individual components of the primary analysis (all-cause mortality and 
cardiovascular-related hospitalisation) also demonstrated significant reductions for tafamidis versus 
placebo. 

The hazard ratio from the all-cause mortality Cox-proportional hazard model for pooled tafamidis was 
0.698 (95% CI 0.508, 0.958), indicating a 30.2% reduction in the risk of death relative to the placebo 
group (p=0.0259). A Kaplan-Meier plot of time to event all-cause mortality is presented in Figure 1.



18

Figure 1: All-cause mortality*

* Heart transplants and cardiac mechanical assist devices treated as death. Hazard ratio from Cox-proportional hazards model with treatment, 
TTR genotype (variant and wild-type), and New York Heart Association (NYHA) Baseline classification (NYHA Classes I and II combined 
and NYHA Class III) as factors.

There were significantly fewer cardiovascular-related hospitalisations with tafamidis compared with 
placebo with a reduction in risk of 32.4% (Table 3).

Table 3: Cardiovascular-related hospitalisation frequency

Pooled Tafamidis
N=264

Placebo
N=177

Total (%) number of subjects with 
Cardiovascular-related hospitalisations

138 (52.3) 107 (60.5)

Cardiovascular-related hospitalisations per year* 0.4750 0.7025
Pooled tafamidis versus placebo treatment 
difference (relative risk ratio)*

0.6761

p-value* < 0.0001
Abbreviation: NYHA=New York Heart Association.
* This analysis was based on a Poisson regression model with treatment, TTR genotype (variant and wild-type), New York Heart Association 
(NYHA) Baseline classification (NYHA Classes I and II combined and NYHA Class III), treatment-by-TTR genotype interaction, and 
treatment-by-NYHA Baseline classification interaction terms as factors. 

The treatment effect of tafamidis on functional capacity and health status was assessed by the 
6-Minute Walk Test (6MWT) and the Kansas City Cardiomyopathy Questionnaire-Overall Summary 
(KCCQ-OS) score (composed of the Total Symptom, Physical Limitation, Quality of Life, and Social 
Limitation domains), respectively. A significant treatment effect favouring tafamidis was first 
observed at Month 6 and remained consistent through Month 30 on both the 6MWT distance and 
KCCQ-OS score (Table 4). 



19

Table 4: 6MWT and KCCQ-OS and component domain scores

Endpoints Baseline Mean (SD) Change from Baseline to 
Month 30, LS mean (SE)

Treatment 
difference 

from placebo 
LS mean 
(95% CI)

p-value

Pooled 
Tafamidis

N=264

Placebo
N=177

Pooled 
Tafamidis 

Placebo

6MWT* 
(metres)

350.55
(121.30)

353.26
(125.98)

-54.87
(5.07)

-130.55
(9.80)

75.68
(57.56, 93.80)

p< 0.0001

KCCQ-OS* 67.27
(21.36)

65.90
(21.74)

-7.16 
(1.42)

-20.81
(1.97)

13.65
(9.48, 17.83)

p< 0.0001

* Higher values indicate better health status.  
Abbreviations: 6MWT=6-Minute Walk Test; KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary; LS=least squares; 
CI=confidence interval.

Results from F-S method represented by win ratio for the combined endpoint and its components 
(all-cause mortality and frequency of cardiovascular-related hospitalisation) consistently favoured 
tafamidis versus placebo by dose and across all subgroups (wild-type, variant and NYHA Class I & II, 
and III) except for cardiovascular-related hospitalisation frequency in NYHA Class III (Figure 2)
which is higher in the tafamidis treated group compared to placebo (see section 4.2). Analyses of 
6MWT and KCCQ-OS also favoured tafamidis relative to placebo within each subgroup.

Figure 2: Results from F-S Method and components by subgroup and dose 

Abbreviations: ATTRm=variant transthyretin amyloid, ATTRwt=wild type transthyretin amyloid, F-S=Finkelstein-Schoenfeld, 
CI=Confidence Interval.
* F-S results presented using win ratio (based on all-cause mortality and frequency of cardiovascular hospitalisation). The Win ratio is the 
number of pairs of treated-patient “wins” divided by number of pairs of placebo patient “wins.”
Heart transplants and cardiac mechanical assist devices treated as death.

In applying the F-S method to each dose group individually, tafamidis reduced the combination of 
all-cause mortality and frequency of cardiovascular-related hospitalisations for both the 80 mg and 
20 mg doses compared to placebo (p=0.0030 and p=0.0048, respectively). Results of the primary 
analysis, 6MWT at Month 30 and KCCQ-OS at Month 30 were statistically significant for both the 
tafamidis meglumine 80 mg and 20 mg doses versus placebo, with similar results for both doses.

Efficacy data for tafamidis 61 mg are not available as this formulation was not evaluated in the 
double-blind, placebo-controlled, randomised phase 3 study. The relative bioavailability of tafamidis 
61 mg is similar to tafamidis meglumine 80 mg at steady-state (see section 5.2).

A supra-therapeutic, single, 400 mg oral dose of tafamidis meglumine solution in healthy volunteers 
demonstrated no prolongation of the QTc interval.

The European Medicines Agency has waived the obligation to submit the results of studies with
tafamidis in all subsets of the paediatric population in transthyretin amyloidosis (see section 4.2 for 
information on paediatric use).



20

5.2 Pharmacokinetic properties 

Absorption

After oral administration of the soft capsule once daily, the maximum peak concentration (Cmax) is 
achieved within a median time (tmax) of 4 hours for tafamidis 61 mg and 2 hours for tafamidis 
meglumine 80 mg (4 x 20 mg) after dosing in the fasted state. Concomitant administration of a high 
fat, high calorie meal altered the rate of absorption, but not the extent of absorption. These results 
support the administration of tafamidis with or without food.

Distribution

Tafamidis is highly protein bound (> 99%) in plasma. The apparent steady-state volume of distribution 
is 18.5 litres. 

The extent of tafamidis binding to plasma proteins has been evaluated using animal and human 
plasma. The affinity of tafamidis for TTR is greater than that for albumin. Therefore, in plasma, 
tafamidis is likely to bind preferentially to TTR despite the significantly higher concentration of 
albumin (600 μM) relative to TTR (3.6 μM).

Biotransformation and elimination

There is no explicit evidence of biliary excretion of tafamidis in humans. Based on preclinical data, it 
is suggested that tafamidis is metabolised by glucuronidation and excreted via the bile. This route of 
biotransformation is plausible in humans, as approximately 59% of the total administered dose is 
recovered in faeces, and approximately 22% recovered in urine. Based on population pharmacokinetic 
results, the apparent oral clearance of tafamidis is 0.263 L/h and the population mean half-life is 
approximately 49 hours.

Dose and time linearity

Exposure from once-daily dosing with tafamidis meglumine increased with increasing dose up to 
480 mg single dose and multiple doses up to 80 mg/day. In general, increases were proportional or 
near proportional to dose and tafamidis clearance was stationary over time.

The relative bioavailability of tafamidis 61 mg is similar to tafamidis meglumine 80 mg at 
steady-state. Tafamidis and tafamidis meglumine are not interchangeable on a per mg basis.

Pharmacokinetic parameters were similar after single and repeated administration of 20 mg dose of 
tafamidis meglumine, indicating a lack of induction or inhibition of tafamidis metabolism.

Results of once-daily dosing with 15 mg to 60 mg oral solution tafamidis meglumine for 14 days 
demonstrated that steady-state was achieved by Day 14.

Special populations

Hepatic impairment

Pharmacokinetic data indicated decreased systemic exposure (approximately 40%) and increased total 
clearance (0.52 L/h versus 0.31 L/h) of tafamidis meglumine in patients with moderate hepatic 
impairment (Child-Pugh Score of 7-9 inclusive) compared to healthy subjects due to a higher unbound 
fraction of tafamidis. As patients with moderate hepatic impairment have lower TTR levels than 
healthy subjects, dosage adjustment is not necessary as the stoichiometry of tafamidis with its target 
protein TTR would be sufficient for stabilisation of the TTR tetramer. The exposure to tafamidis in 
patients with severe hepatic impairment is unknown.



21

Renal impairment

Tafamidis has not specifically been evaluated in a dedicated study of patients with renal impairment. 
The influence of creatinine clearance on tafamidis pharmacokinetics was evaluated in a population 
pharmacokinetic analysis in patients with creatinine clearance greater than 18 mL/min. 
Pharmacokinetic estimates indicated no difference in apparent oral clearance of tafamidis in patients 
with creatinine clearance less than 80 mL/min compared to those with creatinine clearance greater than 
or equal to 80 mL/min. Dosage adjustment in patients with renal impairment is considered not 
necessary.

Elderly

Based on population pharmacokinetic results, subjects ≥ 65 years had an average 15% lower estimate 
of apparent oral clearance at steady-state compared to subjects less than 65 years old. However, the 
difference in clearance results in < 20% increases in mean Cmax and AUC compared to younger 
subjects and is not clinically significant.

Pharmacokinetic/pharmacodynamic relationships

In vitro data indicated that tafamidis does not significantly inhibit cytochrome P450 enzymes 
CYP1A2, CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. Tafamidis is 
not expected to cause clinically relevant drug interaction due to induction of CYP1A2, CYP2B6 or 
CYP3A4.

In vitro studies suggest that it is unlikely tafamidis will cause drug interactions at clinically relevant 
concentrations with substrates of UDP glucuronosyltransferase (UGT) systemically. Tafamidis may 
inhibit intestinal activities of UGT1A1.

Tafamidis showed a low potential to inhibit Multi-Drug Resistant Protein (MDR1) (also known as 
P-glycoprotein; P-gp) systemically and in the gastrointestinal (GI) tract, organic cation transporter 2 
(OCT2), multidrug and toxin extrusion transporter 1 (MATE1) and MATE2K, organic anion 
transporting polypeptide 1B1 (OATP1B1) and OATP1B3 at clinically relevant concentrations. 

5.3 Preclinical safety data 

Nonclinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, fertility and early embryonic development, genotoxicity, and carcinogenic potential. In 
repeat-dose toxicity and the carcinogenicity studies, the liver appeared as a target organ for toxicity in 
the different species tested. Liver effects were seen at exposures approximately equal to the human 
AUC at steady-state at the clinical dose of 61 mg tafamidis.

In a developmental toxicity study in rabbits, a slight increase in skeletal malformations and variations, 
abortions in few females, reduced embryo-foetal survival, and reduction in foetal weights were 
observed at exposures approximately ≥ 2.1 times the human AUC at steady-state at the clinical dose of 
61 mg tafamidis.

In the rat pre- and postnatal development study with tafamidis, decreased pup survival and reduced 
pup weights were noted following maternal dose administration during pregnancy and lactation at 
doses of 15 and 30 mg/kg/day. Decreased pup weights in males were associated with delayed sexual 
maturation (preputial separation) at 15 mg/kg/day. Impaired performance in a water-maze test for 
learning and memory was observed at 15 mg/kg/day. The NOAEL for viability and growth in the F1 
generation offspring following maternal dose administration during pregnancy and lactation with 
tafamidis was 5 mg/kg/day (human equivalent dose of tafamidis = 0.8 mg/kg/day), a dose 
approximately equal to the clinical dose of 61 mg tafamidis.



22

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule shell 

Gelatine (E 441)
Glycerine (E 422)
Red iron oxide (E 172)
Sorbitan
Sorbitol (E 420)
Mannitol (E 421)
Purified water

Capsule contents 

Macrogol 400 (E 1521)
Polysorbate 20 (E 432)
Povidone (K-value 90)
Butylated hydroxytoluene (E 321)

Printing ink (Opacode white)

Ethyl alcohol
Isopropyl alcohol
Purified water
Macrogol 400 (E 1521)
Polyvinyl acetate phthalate
Propylene glycol (E 1520)
Titanium dioxide (E 171)
Ammonium hydroxide (E 527) 28%

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

None.

6.5 Nature and contents of container

PVC/PA/alu/PVC-alu/PET/Paper perforated unit dose blisters.

Pack sizes: a pack of 30 x 1 soft capsules and a multipack containing 90 (3 packs of 30 x 1) soft 
capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.



23

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/003
EU/1/11/717/004

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 16 November 2011
Date of latest renewal: 22 July 2016

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu.

http://www.ema.europa.eu/


24

ANNEX II

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT

E. SPECIFIC OBLIGATION TO COMPLETE 
POST-AUTHORISATION MEASURES FOR THE 
MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES



25

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Penn Pharmaceutical Services Limited
Units 23-24, Tafarnaubach Industrial Estate
Tafarnaubach
Tredegar
Gwent
NP22 3AA
United Kingdom

Or

Millmount Healthcare Limited
Block-7, City North Business Campus,
Stamullen,
Co. Meath,
Ireland

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



26

 Additional risk minimisation measures

Prior to the launch of Vyndaqel (tafamidis) in each Member State, the MAH must agree on the content 
and format of the Healthcare Professional Guide, including communication media, distribution 
modalities, and any other aspects of the programme, with the National Competent Authority.

The Healthcare Professional Guide is aimed at raising prescribers awareness around:
- The need to counsel patients on appropriate precautions when using tafamidis, particularly the 

avoidance of pregnancy and the need to use effective contraception methods.
- Advising female patients to inform their doctor immediately in case of exposure to tafamidis 

during (or within 1 month prior to) pregnancy for physicians’ reporting and assessment.
- Joining the Tafamidis Enhanced Surveillance for Pregnancy Outcomes (TESPO) program in 

case of exposure to tafamidis during pregnancy to collect additional data on pregnancy outcome, 
birth, neonate/infant health and 12 month follow-up with milestones reached; details on how to 
report pregnancies for women receiving Vyndaqel (tafamidis) will be provided.

- Advising patients to contact their doctor about any adverse events while taking tafamidis and 
reminding physicians and pharmacists of the requirement to report suspected adverse reactions 
related to Vyndaqel (tafamidis).

- The clinical criteria for the diagnosis of ATTR-CM before prescribing tafamidis, to avoid 
administration to non-qualifying patients.

- Encouraging patients to enter the Transthyretin-Associated Amyloidosis Outcome Survey 
(THAOS). Details will be provided on how to enroll patients into this international disease 
registry through participating sites (list of EU participating sites will be provided).

The MAH shall ensure that in each Member State where tafamidis is marketed, all Healthcare 
Professionals who are expected to prescribe tafamidis have access to/are provided with the following 
educational material:

The Healthcare Professional Guide with a list of EU participating sites for the 
Transthyretin-Associated Amyloidosis Outcome Survey (THAOS) study.

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES

This being an approval under exceptional circumstances and pursuant to Article 14(8) of Regulation 
(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measure:

Description Due date

Within the planned post-authorisation sub-study of the THAOS registry the 
MAH shall evaluate in non-V30M patients the effects of Vyndaqel on disease 
progression and its long term safety as detailed in a CHMP agreed protocol, and 
shall provide yearly updates on the collected data within the annual re-
assessment.

Annual 
Reassessment 



27

ANNEX III

LABELLING AND PACKAGE LEAFLET



28

A. LABELLING



29

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON 

Pack of 30 x 1 soft capsules – WITH BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 20 mg soft capsules
tafamidis meglumine

2. STATEMENT OF ACTIVE SUBSTANCES

Each soft capsule contains 20 mg micronized tafamidis meglumine equivalent to 12.2 mg tafamidis.

3. LIST OF EXCIPIENTS

The capsule contains sorbitol (E 420). See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

30 x 1 soft capsules

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use
To remove capsule: tear off one individual blister, peel the paper at the curved arrow and push through 
the aluminium foil.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 25°C.



30

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Vyndaqel 20 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC {number}
SN {number}
NN {number}



31

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON 

Multipack of 90 (3 packs of 30 x 1) soft capsules – WITH BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 20 mg soft capsules
tafamidis meglumine

2. STATEMENT OF ACTIVE SUBSTANCES

Each soft capsule contains 20 mg micronized tafamidis meglumine equivalent to 12.2 mg tafamidis.

3. LIST OF EXCIPIENTS

The capsule contains sorbitol (E 420). See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Multipack: 90 (3 packs of 30 x 1) soft capsules.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use
To remove capsule: tear off one individual blister, peel the paper at the curved arrow and push through 
the aluminium foil.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 25°C.



32

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Vyndaqel 20 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC {number}
SN {number}
NN {number}



33

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INNER CARTON 

Pack of 30 – for multipack of 90 (3 packs of 30 x 1) soft capsules – WITHOUT BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 20 mg soft capsules
tafamidis meglumine

2. STATEMENT OF ACTIVE SUBSTANCES

Each soft capsule contains 20 mg micronized tafamidis meglumine equivalent to 12.2 mg tafamidis.

3. LIST OF EXCIPIENTS

The capsule contains sorbitol (E 420). See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

30 x 1 soft capsules. Component of a multipack, can’t be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use
To remove capsule: tear off one individual blister, peel the paper at the curved arrow and push through 
the aluminium foil.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 25°C.



34

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Vyndaqel 20 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

Not applicable.



35

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER

Perforated unit dose blisters of 10 x 20 mg Vyndaqel soft capsules

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 20 mg soft capsules
tafamidis meglumine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG (as MA Holder logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



36

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON 

Pack of 30 x 1 soft capsules – WITH BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 61 mg soft capsules
tafamidis

2. STATEMENT OF ACTIVE SUBSTANCES

Each soft capsule contains 61 mg micronized tafamidis.

3. LIST OF EXCIPIENTS

The capsule contains sorbitol (E 420). See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

30 x 1 soft capsules

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use
To remove capsule: tear off one individual blister, peel the paper at the curved arrow and push through 
the aluminium foil.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



37

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/003

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Vyndaqel 61 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC {number}
SN {number}
NN {number}



38

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON 

Multipack of 90 (3 packs of 30 x 1) soft capsules – WITH BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 61 mg soft capsules
tafamidis

2. STATEMENT OF ACTIVE SUBSTANCES

Each soft capsule contains 61 mg micronized tafamidis.

3. LIST OF EXCIPIENTS

The capsule contains sorbitol (E 420). See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Multipack: 90 (3 packs of 30 x 1) soft capsules.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use
To remove capsule: tear off one individual blister, peel the paper at the curved arrow and push through 
the aluminium foil.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



39

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/004

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Vyndaqel 61 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC {number}
SN {number}
NN {number}



40

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INNER CARTON 

Pack of 30 – for multipack of 90 (3 packs of 30 x 1) soft capsules – WITHOUT BLUE BOX

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 61 mg soft capsules
tafamidis

2. STATEMENT OF ACTIVE SUBSTANCES

Each soft capsule contains 61 mg micronized tafamidis.

3. LIST OF EXCIPIENTS

The capsule contains sorbitol (E 420). See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

30 x 1 soft capsules. Component of a multipack, can’t be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use
To remove capsule: tear off one individual blister, peel the paper at the curved arrow and push through 
the aluminium foil.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



41

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/717/004

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Vyndaqel 61 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

Not applicable.



42

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER

Perforated unit dose blisters of 10 x 61 mg Vyndaqel soft capsules

1. NAME OF THE MEDICINAL PRODUCT

Vyndaqel 61 mg soft capsules
tafamidis

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG (as MA Holder logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



43

B. PACKAGE LEAFLET



44

Package leaflet: Information for the user

Vyndaqel 20 mg soft capsules
tafamidis meglumine

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

1. What Vyndaqel is and what it is used for

Vyndaqel contains the active substance tafamidis.

Vyndaqel is a medicine which treats a disease called transthyretin amyloidosis Transthyretin 
amyloidosis is caused by a protein called transthyretin (TTR) that does not work properly. TTR is a 
protein that carries other substances, such as hormones, through the body.

In patients with this disease, TTR breaks up and may form fibres called amyloid. Amyloid can build 
up around your nerves (known as transthyretin amyloid polyneuropathy or ATTR-PN) and in other 
places in your body. The amyloid causes the symptoms of this disease. When this occurs, it prevents
them from working normally. 

Vyndaqel, can prevent TTR from breaking up and forming amyloid. This medicine is used to treat 
adult patients with this disease whose nerves have been affected (people with symptomatic
polyneuropathy) to delay further progression.

2. What you need to know before you take Vyndaqel

Do not take Vyndaqel

If you are allergic to tafamidis meglumine or any of the other ingredients of this medicine (listed in 
section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Vyndaqel.



45

 Women that can become pregnant should use birth control while taking Vyndaqel and should 
continue using birth control for one month after stopping treatment with Vyndaqel. There are no 
data on the use of Vyndaqel in pregnant women.

Children and adolescents

Children and adolescents do not have the symptoms of transthyretin amyloidosis. Vyndaqel is 
therefore not used for children and adolescents.

Other medicines and Vyndaqel

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.

You should inform your doctor or pharmacist if you are taking any of the following:

- non-steroidal anti-inflammatory drugs
- diuretic medicines (e.g. furosemide, bumetanide) 
- anti-cancer medicines (e.g. methotrexate, imatinib)
- statins (e.g. rosuvastatin)
- anti-viral medicines (e.g. oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, lamivudine, 

zidovudine, zalcitabine)

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.

 You should not take Vyndaqel if you are pregnant or breast-feeding.
 If you are able to become pregnant, you must use birth control during treatment and for 

one month after stopping treatment.

Driving and using machines

Vyndaqel is believed to have no or negligible influence on the ability to drive and use machines.

Vyndaqel contains sorbitol

This medicine contains no more than 44 mg sorbitol in each capsule.

3. How to take Vyndaqel

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

The recommended dose is one Vyndaqel 20 mg (tafamidis meglumine) capsule taken once a day.

If you vomit after taking this medicine and can identify the intact Vyndaqel capsule, then an additional 
dose of Vyndaqel should be taken in the same day; if you cannot identify the Vyndaqel capsule, then 
no additional dose of Vyndaqel is necessary, and you can resume taking Vyndaqel the next day as 
usual.

Method of administration

Vyndaqel is for oral use.
The soft capsule should be swallowed whole, not crushed or cut.



46

The capsule may be taken with or without food.

Instructions for opening the blisters

 Tear off one individual blister from the blister card along the perforated line.
 Peel back the paper at the curved arrow to expose the aluminium foil.
 Push capsule through the exposed aluminium foil.

If you take more Vyndaqel than you should

You should not take more capsules than your doctor tells you to. If you take more capsules than you 
have been told to take, contact your doctor.

If you forget to take Vyndaqel

If you forget to take a dose, take your capsules as soon as you remember. If it is within 6 hours before
your next dose, skip the missed dose and take the next dose at the usual time. Do not take a double 
dose to make up for a forgotten dose.

If you stop taking Vyndaqel

Do not stop taking Vyndaqel without first speaking to your doctor. As Vyndaqel works by stabilising 
the TTR protein, if you stop taking Vyndaqel, the protein will no longer be stabilised, and your disease 
may progress.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Very common: may affect more than 1 in 10 people are listed below:
 Diarrhoea
 Urinary tract infection (symptoms may include: pain or a burning sensation when you urinate or 

a frequent need to urinate)
 Vaginal infection in women
 Stomach ache or abdominal pain

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Vyndaqel

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister card and on the carton. The 
expiry date refers to the last day of that month.

Do not store above 25°C.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


47

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Vyndaqel contains

 The active substance is tafamidis. Each capsule contains 20 mg micronized tafamidis 
meglumine equivalent to 12.2 mg tafamidis.

 The other ingredients are: gelatine (E 441), glycerine (E 422), sorbitol (E 420) [see section 2], 
mannitol (E 421), sorbitan, yellow iron oxide (E 172), titanium dioxide (E 171), purified water, 
macrogol 400 (E 1521), sorbitan monooleate (E 494), polysorbate 80 (E 433), ethyl alcohol, 
isopropyl alcohol, polyvinyl acetate phthalate, propylene glycol (E 1520), carmine (E 120), 
brilliant blue FCF (E 133) and ammonium hydroxide (E 527).

What Vyndaqel looks like and contents of the pack

Vyndaqel soft capsules are yellow, opaque, oblong (approximately 21 mm) printed with “VYN 20” in 
red. Vyndaqel is available in two pack sizes of PVC/PA/alu/PVC-alu/PET/Paper perforated unit dose 
blisters: a pack of 30 x 1 soft capsules and a multipack of 90 soft capsules comprising of 3 cartons, 
each containing 30 x 1 soft capsules. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Penn Pharmaceutical Services Limited
Units 23-24, Tafarnaubach Industrial Estate
Tafarnaubach
Tredegar
Gwent
NP22 3AA
United Kingdom

Or

Millmount Healthcare Limited
Block-7, City North Business Campus,
Stamullen,
Co. Meath,
Ireland

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

België/Belgique/Belgien
Pfizer S.A. / N.V.
Tél/Tel: +32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

България
Пфайзер Люксембург САРЛ, Клон България
Тел.: +359 2 970 4333

Luxembourg/Luxemburg
Pfizer S.A. 
Tél/Tel: +32 (0)2 554 62 11

Česká Republika
Pfizer PFE, spol. s r.o. 
Tel: +420 283 004 111

Magyarország
Pfizer Kft.
Tel: +36 1 488 3700



48

Danmark
Pfizer ApS
Tlf: +45 44 20 11 00

Malta
Vivian Corporation Ltd.
Tel: +356 21344610

Deutschland
Pfizer Pharma GmbH
Tel: +49 (0)30 550055-51000

Nederland
Pfizer bv
Tel: +31 (0)10 406 43 01

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Norge
Pfizer Norge AS
Tlf: +47 67 52 61 00

Ελλάδα
PFIZER ΕΛΛΑΣ Α.Ε., 
Τηλ.: +30 210 67 85 800

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

España
Pfizer, S.L.
Télf: +34 91 490 99 00

Polska
Pfizer Polska Sp. z o.o.,
Tel.: +48 22 335 61 00

France
Pfizer
Tél +33 (0)1 58 07 34 40

Portugal
Pfizer Biofarmacêutica, Sociedade Unipessoal 
Lda
Tel: +351 21 423 5500

Hrvatska
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

România
Pfizer Romania S.R.L
Tel: +40 (0)21 207 28 00

Ireland
Pfizer Healthcare Ireland
Tel: +353 1800 633 363 (toll free)
Tel: +44 (0)1304 616161

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0)1 52 11 400

Ísland
Icepharma hf.
Tel: +354 540 8000

Slovenská Republika
Pfizer Luxembourg SARL, organizačná zložka 
Tel: +421 2 3355 5500

Italia
Pfizer S.r.l.
Tel: +39 06 33 18 21

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Κύπρος
PFIZER ΕΛΛΑΣ Α.Ε. (CYPRUS BRANCH), 
Τηλ: +357 22 817690

Sverige 
Pfizer Innovations AB
Tel: +46 (0)8 550 520 00

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

United Kingdom
Pfizer Limited
Tel: +44 (0)1304 616161

This leaflet was last revised in <{MM/YYYY}><{month YYYY}>.

This medicine has been authorised under ‘exceptional circumstances’.
This means that because of the rarity of this disease it has been impossible to get complete information 
on this medicine.



49

The European Medicines Agency will review any new information on this medicine every year and 
this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

If this leaflet is difficult to see or read or you would like it in a different format, please contact the 
Marketing Authorisation Holder’s local office number that is provided in this leaflet.

http://www.ema.europa.eu/


50

Package leaflet: Information for the user

Vyndaqel 61 mg soft capsules
tafamidis

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

1. What Vyndaqel is and what it is used for

Vyndaqel contains the active substance tafamidis.

Vyndaqel is a medicine which treats a disease called transthyretin amyloidosis. Transthyretin 
amyloidosis is caused by a protein called transthyretin (TTR) that does not work properly. TTR is a 
protein that carries other substances, such as hormones, through the body.

In patients with this disease, TTR breaks up and may form fibres called amyloid. Amyloid can build 
up between cells in your heart (known as transthyretin amyloid cardiomyopathy or ATTR-CM) and in 
other places in your body. The amyloid causes the symptoms of this disease. When this occurs in your 
heart, it prevents your heart from working normally.

Vyndaqel, can prevent TTR from breaking up and forming amyloid. This medicine is used to treat 
adult patients whose heart has been affected (people with symptomatic cardiomyopathy).

2. What you need to know before you take Vyndaqel

Do not take Vyndaqel

If you are allergic to tafamidis or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Vyndaqel.



51

 Women that can become pregnant should use birth control while taking Vyndaqel and should 
continue using birth control for one month after stopping treatment with Vyndaqel. There are no 
data on the use of Vyndaqel in pregnant women.

Children and adolescents

Children and adolescents do not have the symptoms of transthyretin amyloidosis. Vyndaqel is 
therefore not used for children and adolescents.

Other medicines and Vyndaqel

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.

You should inform your doctor or pharmacist if you are taking any of the following:

- non-steroidal anti-inflammatory drugs
- diuretic medicines (e.g. furosemide, bumetanide) 
- anti-cancer medicines (e.g. methotrexate, imatinib)
- statins (e.g. rosuvastatin)
- anti-viral medicines (e.g. oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, lamivudine, 

zidovudine, zalcitabine)

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.

 You should not take Vyndaqel if you are pregnant or breast-feeding.
 If you are able to become pregnant, you must use birth control during treatment and for 

one month after stopping treatment.

Driving and using machines

Vyndaqel is believed to have no or negligible influence on the ability to drive and use machines.

Vyndaqel contains sorbitol

This medicine contains no more than 44 mg sorbitol in each capsule.

3. How to take Vyndaqel

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

The recommended dose is one Vyndaqel 61 mg (tafamidis) capsule taken once a day.

If you vomit after taking this medicine and can identify the intact Vyndaqel capsule, then an additional 
dose of Vyndaqel should be taken in the same day; if you cannot identify the Vyndaqel capsule, then 
no additional dose of Vyndaqel is necessary, and you can resume taking Vyndaqel the next day as 
usual.

Method of administration

Vyndaqel is for oral use.
The soft capsule should be swallowed whole, not crushed or cut.



52

The capsule may be taken with or without food.

Instructions for opening the blisters

 Tear off one individual blister from the blister card along the perforated line.
 Peel back the paper at the curved arrow to expose the aluminium foil.
 Push capsule through the exposed aluminium foil.

If you take more Vyndaqel than you should

You should not take more capsules than your doctor tells you to. If you take more capsules than you 
have been told to take, contact your doctor.

If you forget to take Vyndaqel

If you forget to take a dose, take your capsules as soon as you remember. If it is within 6 hours before
your next dose, skip the missed dose and take the next dose at the usual time. Do not take a double 
dose to make up for a forgotten dose.

If you stop taking Vyndaqel

Do not stop taking Vyndaqel without first speaking to your doctor. As Vyndaqel works by stabilising 
the TTR protein, if you stop taking Vyndaqel, the protein will no longer be stabilised, and your disease 
may progress.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In clinical studies, the side effects in patients taking Vyndaqel were generally similar to that of patients 
not taking Vyndaqel. Flatulence and increase in liver function tests were reported more often in 
ATTR-CM patients treated with Vyndaqel.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Vyndaqel

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister card and on the carton. The 
expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


53

6. Contents of the pack and other information

What Vyndaqel contains

 The active substance is tafamidis. Each capsule contains 61 mg micronized tafamidis.

 The other ingredients are: gelatine (E 441), glycerine (E 422), sorbitol (E 420) [see section 2], 
mannitol (E 421), sorbitan, red iron oxide (E 172), purified water, macrogol 400 (E 1521), 
polysorbate 20 (E 432), povidone (K-value 90), butylated hydroxytoluene (E321), ethyl alcohol, 
isopropyl alcohol, polyvinyl acetate phthalate, propylene glycol (E 1520), titanium dioxide 
(E 171), and ammonium hydroxide (E 527).

What Vyndaqel looks like and contents of the pack

Vyndaqel soft capsules are reddish brown, opaque, oblong (approximately 21 mm) printed with 
“VYN 61” in white. Vyndaqel is available in two pack sizes of PVC/PA/alu/PVC-alu/PET/Paper 
perforated unit dose blisters: a pack of 30 x 1 soft capsules and a multipack of 90 soft capsules 
comprising of 3 cartons, each containing 30 x 1 soft capsules. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Millmount Healthcare Limited
Block-7, City North Business Campus,
Stamullen,
Co. Meath,
Ireland 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

België/Belgique/Belgien
Pfizer S.A. / N.V.
Tél/Tel: +32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

България
Пфайзер Люксембург САРЛ, Клон България
Тел.: +359 2 970 4333

Luxembourg/Luxemburg
Pfizer S.A. 
Tél/Tel: +32 (0)2 554 62 11

Česká Republika
Pfizer PFE, spol. s r.o. 
Tel: +420 283 004 111

Magyarország
Pfizer Kft.
Tel: +36 1 488 3700

Danmark
Pfizer ApS
Tlf: +45 44 20 11 00

Malta
Vivian Corporation Ltd.
Tel: +356 21344610

Deutschland
Pfizer Pharma GmbH
Tel: +49 (0)30 550055-51000

Nederland
Pfizer bv
Tel: +31 (0)10 406 43 01

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Norge
Pfizer Norge AS
Tlf: +47 67 52 61 00



54

Ελλάδα
PFIZER ΕΛΛΑΣ Α.Ε., 
Τηλ.: +30 210 67 85 800

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

España
Pfizer, S.L.
Télf: +34 91 490 99 00

Polska
Pfizer Polska Sp. z o.o.,
Tel.: +48 22 335 61 00

France
Pfizer
Tél +33 (0)1 58 07 34 40

Portugal
Pfizer Biofarmacêutica, Sociedade Unipessoal 
Lda
Tel: +351 21 423 5500

Hrvatska
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

România
Pfizer Romania S.R.L
Tel: +40 (0)21 207 28 00

Ireland
Pfizer Healthcare Ireland
Tel: +353 1800 633 363 (toll free)
Tel: +44 (0)1304 616161

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0)1 52 11 400

Ísland
Icepharma hf.
Tel: +354 540 8000

Slovenská Republika
Pfizer Luxembourg SARL, organizačná zložka 
Tel: +421 2 3355 5500

Italia
Pfizer S.r.l.
Tel: +39 06 33 18 21

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Κύπρος
PFIZER ΕΛΛΑΣ Α.Ε. (CYPRUS BRANCH), 
Τηλ: +357 22 817690

Sverige 
Pfizer Innovations AB
Tel: +46 (0)8 550 520 00

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

United Kingdom
Pfizer Limited
Tel: +44 (0)1304 616161

This leaflet was last revised in <{MM/YYYY}>.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

If this leaflet is difficult to see or read or you would like it in a different format, please contact the 
Marketing Authorisation Holder’s local office number that is provided in this leaflet.

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E.  SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET