What are the side effects of Vyndamax (Tafamidis)?

From the Guidelines

Vyndamax (tafamidis) can cause several side effects, though many patients tolerate it well, and it is essential to weigh these against its benefits in reducing morbidity and mortality in patients with transthyretin amyloidosis. Common side effects include respiratory tract infections, urinary tract infections, diarrhea, and peripheral edema (swelling in the extremities) 1. Some patients may experience dizziness, headache, or nausea. More serious but less common side effects can include heart rhythm abnormalities and liver function test abnormalities. If you're taking Vyndamax, it's crucial to report any unusual symptoms to your healthcare provider promptly, especially shortness of breath, unusual fatigue, swelling, or heart palpitations.

These side effects occur because Vyndamax works by stabilizing transthyretin proteins to prevent amyloid formation in the heart, and this mechanism can affect other bodily systems. Regular monitoring by your healthcare provider is essential while on this medication to catch any potential issues early. The standard dose is 61 mg once daily, and the medication should be taken as prescribed even if side effects are mild. It's also important to note that tafamidis has been shown to improve cardiovascular outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), with lower all-cause mortality and lower cardiovascular-related hospitalization compared to placebo 1.

In terms of management, patients with ATTR-CM and reduced ejection fraction may not tolerate traditional heart failure medications well due to the risk of exacerbating hypotension or worsening heart failure symptoms 2. Therefore, the use of Vyndamax and other medications should be carefully considered and monitored by a healthcare provider. Additionally, the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for patients with cardiac amyloidosis highlights the importance of disease-directed therapy and symptom management in patients with amyloid neuropathy, including the use of tafamidis and other TTR stabilizers or silencers 3.

Overall, while Vyndamax can cause side effects, its benefits in reducing morbidity and mortality in patients with transthyretin amyloidosis make it a crucial medication for many patients, and regular monitoring and careful management can help minimize its risks. The most recent and highest quality evidence supports the use of Vyndamax at a dose of 61 mg once daily, with careful monitoring for side effects and adjustment of treatment as needed 1.

From the FDA Drug Label

6. ADVERSE REACTIONS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice The data reflect exposure of 377 ATTR-CM patients to 20 mg or 80 mg (administered as four 20-mg capsules) of VYNDAQEL administered daily for an average of 24. 5 months (ranging from 1 day to 111 months). Adverse events were assessed from ATTR-CM clinical trials with VYNDAQEL, primarily a 30-month placebo-controlled trial [see Clinical Studies (14)]. The frequency of adverse events in patients treated with VYNDAQEL 20 mg (n=88) or 80 mg (n=176; administered as four 20-mg capsules) was similar to that with placebo (n=177) In the 30-month placebo-controlled trial, similar proportions of VYNDAQEL-treated patients and placebo-treated patients discontinued the study drug because of an adverse event: 12 (7%), 5 (6%), and 11 (6%) from the VYNDAQEL 80-mg, VYNDAQEL 20-mg, and placebo groups, respectively.

The most common adverse events for Vyndamax (tafamidis) are not explicitly stated in the provided text, but it is mentioned that the frequency of adverse events in patients treated with VYNDAQEL (which contains the same active ingredient as VYNDAMAX) was similar to that with placebo.

• The discontinuation rates due to adverse events were also similar between VYNDAQEL-treated patients and placebo-treated patients. However, the exact side effects of Vyndamax are not directly provided in the given text 4.

From the Research

Vyndamax Side Effects

• The studies 5, 6, 7 suggest that Vyndamax (tafamidis) is generally well tolerated in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and has a safety profile similar to that of placebo.
• The incidence and types of adverse events were similar in the tafamidis and placebo groups in the ATTR-ACT trial 6.
• Tafamidis was found to have fewer adverse events, with no difference found compared with placebo 5.
• The most common adverse events associated with tafamidis were not specified in the studies, but it was noted that tafamidis is suitable for long-term use 7.

Mechanism of Action and Efficacy

• Tafamidis stabilizes both wild-type and mutant transthyretin (TTR), inhibiting the formation of TTR amyloid fibrils 7, 8.
• Tafamidis binds to the thyroxine-binding sites of the TTR tetramer and inhibits its dissociation into monomers, which is the rate-limiting step in the amyloidogenic process 5, 8.
• Treatment with tafamidis was significantly associated with a reduction in mortality, lowered cardiovascular-related hospitalizations, less functional decline, and improved TTR stabilization compared with placebo 5, 6.

Clinical Application

• Tafamidis is approved for the treatment of adults with ATTR-CM and has been shown to reduce all-cause mortality and frequency of cardiovascular-related hospitalizations relative to placebo 6, 7.
• Tafamidis is also approved for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP) and has been shown to slow disease progression and reduce the burden of disease 9, 8.