Vyndamax

Other Cardiovascular Agents

 
NOTE: Prescribers and patients may participate in the voluntary Transthyretin Amyloidosis Outcome Survey (THAOS) registry, a longitudinal, observational survey to obtain additional clinical data on this condition. Information regarding this registry may be found at https://clinicaltrials.gov.

Vyndaqel and Vyndamax are not equivalent on a mg-per-mg basis.
Swallow capsules whole. Do not crush or chew.
Do not double doses. Take missed doses as soon as remembered or skip the dose and take at next regularly scheduled time.[64127]

Vyndamax, Vyndaqel

Rx

Selective stabilizer of transthyretin (TTR) for cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults
Reduces cardiovascular mortality and cardiovascular-related hospitalizations
Potential to cause fetal harm; advise women of child-bearing potential to use contraception during therapy

80 mg (four 20 mg capsules) PO once daily. Tafamidis therapy is recommended for patients with wild type or hereditary transthyretin-mediated amyloidosis and NYHA class I to III symptoms. No benefit has been observed with tafamidis therapy in patients with NYHA class IV symptoms, severe aortic stenosis, or impaired renal function (defined as a glomerular filtration rate less than 25 mL/min/1.73 m2 body surface area).  

61 mg PO once daily. Tafamidis therapy is recommended for patients with wild type or hereditary transthyretin-mediated amyloidosis and NYHA class I to III symptoms. No benefit has been observed with tafamidis therapy in patients with NYHA class IV symptoms, severe aortic stenosis, or impaired renal function (defined as a glomerular filtration rate less than 25 mL/min/1.73 m2 body surface area).  

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abacavir; Dolutegravir; Lamivudine: (Moderate) Caution is advised with the coadministration of tafamidis and dolutegravir as coadministration may increase the plasma concentrations of dolutegravir increasing the risk of adverse effects. Dolutegravir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Alpelisib: (Major) Avoid coadministration of alpelisib with tafamidis due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and tafamidis is a BCRP inhibitor.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking tafamidis. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a BCRP substrate and tafamidis is a BCRP inhibitor. Coadministration with another BCRP inhibitor increased berotralstat exposure by 69%.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Dolutegravir: (Moderate) Caution is advised with the coadministration of tafamidis and dolutegravir as coadministration may increase the plasma concentrations of dolutegravir increasing the risk of adverse effects. Dolutegravir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Dolutegravir; Lamivudine: (Moderate) Caution is advised with the coadministration of tafamidis and dolutegravir as coadministration may increase the plasma concentrations of dolutegravir increasing the risk of adverse effects. Dolutegravir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Caution is advised with the coadministration of tafamidis and dolutegravir as coadministration may increase the plasma concentrations of dolutegravir increasing the risk of adverse effects. Dolutegravir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of tafamidis and glecaprevir as coadministration may increase the plasma concentrations of glecaprevir increasing the risk of adverse effects. Glecaprevir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. (Moderate) Caution is advised with the coadministration of tafamidis and pibrentasvir due to the potential for increased plasma concentrations of pibrentasvir increasing the risk of adverse effects. Pibrentasvir dose adjustment may be needed with coadministration. Pibrentasvir is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Glyburide: (Moderate) Caution is advised with the coadministration of tafamidis and glyburide due to the potential for increased plasma concentrations of glyburide resulting in increased risk of adverse effects. Glyburide dose adjustment may be needed with coadministration. Glyburide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Glyburide; Metformin: (Moderate) Caution is advised with the coadministration of tafamidis and glyburide due to the potential for increased plasma concentrations of glyburide resulting in increased risk of adverse effects. Glyburide dose adjustment may be needed with coadministration. Glyburide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Imatinib: (Moderate) Caution is advised with the coadministration of tafamidis and imatinib due to the potential for increased plasma concentrations of imatinib resulting increasing the risk of adverse effects. Imatinib dose adjustment may be needed with coadministration. Imatinib is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Caution is advised with the coadministration of tafamidis and ledipasvir due to the potential for increased plasma concentrations of ledipasvir increasing the risk of adverse effects. Ledipasvir dose adjustment may be needed with coadministration. Ledipasvir is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. (Minor) Caution is advised with the coadministration of tafamidis and sofosbuvir as coadminstration may increase the plasma concentrations of sofosbuvir and increase the risk of adverse effects. Sofosbuvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Methotrexate: (Moderate) Caution is advised with the coadministration of tafamidis and methotrexate due to the potential for increased plasma concentrations of methotrexate increasing the risk of adverse effects. Methotrexate dose adjustment may be needed with coadministration. Methotrexate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Pazopanib: (Moderate) Caution is advised with the coadministration of tafamidis and pazopanib due to the potential for increased plasma concentrations of pazopanib increasing the risk of adverse effects. Pazopanib dose adjustment may be needed with coadministration. Pazopanib is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Prazosin: (Moderate) Caution is advised with the coadministration of tafamidis and prazosin due to the potential for increased plasma concentrations of prazosin increasing the risk of adverse effects. Prazosin dose adjustment may be needed with coadministration. Prazosin is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Rosuvastatin: (Major) Avoid concomitant use of rosuvastatin and tafamidis. Concomitant use may increase rosuvastatin exposure and the risk for rosuvastatin-related adverse reactions, such as myopathy and rhabdomyolysis. If concomitant use is necessary, initiate rosuvastatin at 5 mg once daily and do not exceed a rosuvastatin dose of 20 mg once daily; monitor for adverse effects. Rosuvastatin is a BCRP substrate and tafamidis is a BCRP inhibitor. Coadministration with tafamidis increased rosuvastatin exposure by almost 2-fold.
Rosuvastatin; Ezetimibe: (Major) Avoid concomitant use of rosuvastatin and tafamidis. Concomitant use may increase rosuvastatin exposure and the risk for rosuvastatin-related adverse reactions, such as myopathy and rhabdomyolysis. If concomitant use is necessary, initiate rosuvastatin at 5 mg once daily and do not exceed a rosuvastatin dose of 20 mg once daily; monitor for adverse effects. Rosuvastatin is a BCRP substrate and tafamidis is a BCRP inhibitor. Coadministration with tafamidis increased rosuvastatin exposure by almost 2-fold.
Sofosbuvir: (Minor) Caution is advised with the coadministration of tafamidis and sofosbuvir as coadminstration may increase the plasma concentrations of sofosbuvir and increase the risk of adverse effects. Sofosbuvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Sofosbuvir; Velpatasvir: (Minor) Caution is advised with the coadministration of tafamidis and sofosbuvir as coadminstration may increase the plasma concentrations of sofosbuvir and increase the risk of adverse effects. Sofosbuvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. (Minor) Caution is advised with the coadministration of tafamidis and velpatasvir as coadministration may increase plasma concentrations of velpatasvir and increase the risk of adverse effects. Velpatasvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Minor) Caution is advised with the coadministration of tafamidis and sofosbuvir as coadminstration may increase the plasma concentrations of sofosbuvir and increase the risk of adverse effects. Sofosbuvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. (Minor) Caution is advised with the coadministration of tafamidis and velpatasvir as coadministration may increase plasma concentrations of velpatasvir and increase the risk of adverse effects. Velpatasvir is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Sulfasalazine: (Moderate) Caution is advised with the coadministration of tafamidis and sulfasalazine due to the potential for increased plasma concentrations of sulfasalazine increasing the risk of adverse effects. Sulfasalazine dose adjustment may be needed with coadministration. Sulfasalazine is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of tafamidis is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and tafamidis is a BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir alafenamide due to the potential for increased plasma concentrations of tenofovir alafenamide increasing the risk of adverse effects. Tenofovir alafenamide dose adjustment may be needed with coadministration. Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised with the coadministration of tafamidis and tenofovir disoproxil fumarate due to the potential for increased plasma concentrations of tenofovir disoproxil fumarate increasing the risk of adverse effects. Tenofovir disoproxil fumarate dose adjustment may be needed with coadministration. Tenofovir disoproxil fumarate is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.
Topotecan: (Major) Avoid coadministration of tafamidis with oral topotecan due to increased topotecan exposure; tafamidis may be administered with intravenous topotecan. Oral topotecan is a substrate of the breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor. Coadministration increases the risk of topotecan-related adverse effects.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with tafamidis. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP drug transporter; tafamidis is a BCRP inhibitor.
Vemurafenib: (Moderate) Caution is advised with the coadministration of tafamidis and vemurafenib due to the potential for increased plasma concentrations of vemurafenib increasing the risk of adverse effects. Vemurafenib dose adjustment may be needed with coadministration. Vemurafenib is a substrate of breast cancer resistance protein (BCRP) and tafamidis is a BCRP inhibitor.

Vyndamax/Vyndaqel Oral Cap: 20mg, 61mg

80 mg once daily (Vyndaqel); 61 mg once daily (Vyndamax).

80 mg once daily (Vyndaqel); 61 mg once daily (Vyndamax).

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Tafamidis is a selective transthyretin (TTR) stabilizer. Transthyretin protein binds and transports less than 10% of circulating thyroxine (T4). TTR also binds holo-retinol-binding protein (retinol-binding protein-vitamin A complex) and facilitates the transport of retinol to tissues; TTR is the only known holo-retinol binding protein transporter. TTR contains monomeric subunits that fold into a tetramer with distinct dimer-dimer interfaces within the cellular endoplasmic reticulum. Point gene mutations result in TTR instability, misfolding, and subsequent dissociation to folded monomers. Transthyretin amyloid fibrils, made up of TTR monomers, accumulate in the myocardium causing transthyretin amyloid cardiomyopathy. Tafamidis exerts its therapeutic effect in the rate-limiting step of the amyloidogenic process by binding to the thyroxine binding sites on TTR, stabilizing the tetramer and slowing monomer dissociation.[64125] [64126] [64127]

Tafamidis is administered orally. Greater than 99% of tafamidis is bound to plasma protein, primarily transthyretin (TTR). Exposure to tafamidis increased proportionally with multiple doses up to 80 mg once daily or a single dose up to 480 mg. The steady-state volume of distribution is reported to be 18.5 L for tafamidis and 16L for tafamidis meglumine. Oral clearance of tafamidis is 0.263 L/hr and tafamidis meglumine is 0.228 L/hr. The mean half-life is 49 hours. Glucuronidation appears to play a role; however, tafamidis metabolism has not been fully elucidated. Following oral administration of a single tafamidis 20 mg dose, approximately 59% of the drug was recovered in the feces as unchanged drug and about 22% in the urine as a glucuronide metabolite.[64127]
 
Affected cytochrome P450 enzymes or transporter: CYP2B6, CYP3A4, UGT1A1, BCRPTafamidis inhibits breast cancer resistant protein (BCRP) and UDP glucuronosyltransferase (UGT1A1). In a study involving healthy subjects, coadministration with tafamidis 61 mg once daily resulted in increases of 96.75% and 85.6% in the AUC and Cmax, respectively, of rosuvastatin, a BCRP substrate. Tafamidis induces CYP2B6 and CYP3A4. Tafamidis does not induce CYP1A2 or inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5, or CYP2D6. In vitro studies suggest a low potential for tafamidis inhibition of organic anion transporters, OAT1 and OAT3.[64127]

The median time to peak plasma concentrations was within 4 hours. Administration with a high-fat, high-calorie meal did not have a clinical impact on pharmacokinetics. Tafamidis meglumine (Vyndaqel) 80 mg (four-20 mg capsules) and tafamidis (Vyndamax) 61 mg were not found to have any clinically significant differences in AUC and Cmax at steady-state.[64127]

Tafamidis has been found to cause fetal harm when administered to pregnant rats and rabbits; however, data on the use of tafamidis during pregnancy in humans is limited. Oral administration of tafamidis at approximately 10 times the maximum human recommended dose (MHRD) to pregnant rats resulted in decreased fetal body weights. The no-observed-adverse-effect-level for teratogenic effects in pregnant rats was found to be at 7 times the MHRD. Tafamidis at doses 2 times MHRD administered to rats during pregnancy and lactation resulted in postnatal mortality, growth retardation, impaired learning, decreased body weight, delayed male sexual maturation, and impaired memory. Increased embryofetal mortality, reduced fetal body weights, and an increased incidence of fetal malformations occurred in pregnant rabbits that received approximately 9 times the MHRD of oral tafamidis; this dose was also found to be maternally toxic. At almost equivalent human tafamidis doses in pregnant rabbits, there was an increased incidence of fetal skeletal variations. Based on the results of animal studies, tafamidis may cause teratogenic effects when administered to pregnant females. Counsel patients on the potential risks of tafamidis to the fetus. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to tafamidis; information about the registry can be obtained by calling 1-800-438-1985. [64127]

The manufacturer recommends against breast-feeding during tafamidis treatment. Data on the presence of tafamidis in human milk, the effect on the breast-fed infant, or the effect on milk production are unavailable.