Vindamex (Capsules) Instructions for Use

Marketing Authorization Holder

Pfizer, Inc. (USA)

Manufactured By

Catalent Pharma Solutions LLC (USA)

Primary Packaging

ANDERSONBRECON, Inc. (USA)

Packaging and Quality Control Release

ANDERSONBRECON (UK), Limited (UK)

ATC Code

N07XX08 (Tafamidis)

Active Substance

Tafamidis (Rec.INN WHO registered)

Dosage Form

Vindamex

Capsules 61 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Capsules are soft gelatin, reddish-brown, oblong, opaque, with a white inscription “VYN 61”; the capsule contents are a white to pink suspension.

Excipients: macrogol 400 – 471.1 mg, polysorbate 80 – 55.5 mg, povidone (K90) – 12 mg, butylated hydroxytoluene – 0.4 mg.

Gelatin shell composition: transparent gelatin (L3DXHBAHR) – 367.9 mg consists of: gelatin (195 Acid type) – 217.3 mg, sorbitol special glycerin mixture – 150.6 mg; iron oxide red dye (E172) – 1.29 mg.
The amount of solids from the printing ink remaining on the capsule is trace (not more than 0.8 mg/capsule).
The inscription “VYN 61” is applied with white ink Opacode^® (WB) NSP-78-18022.
Colorcon^® Ink, White Opacode^® (WB) NSP-78-18022 contains the following components: alcohol SDA 35A* (24.9% w/w), ammonium hydroxide* 28% (0.9% w/w), isopropanol* (8.2% w/w), purified water* (9.9% w/w), macrogol MW400 (polyethylene glycol) (2.3% w/w), polyvinyl acetate phthalate (10.4% w/w), propylene glycol (24% w/w), titanium dioxide (19.6% w/w).

* removed during the manufacturing process and absent in the final product.
Soy lecithin and triglycerides are used in the manufacturing process as lubricants for the gelatin band.

10 pcs. – blisters (3) – cardboard packs with first-opening control.

Clinical-Pharmacological Group

Selective transthyretin stabilizer to slow the progression of amyloid polyneuropathy

Pharmacotherapeutic Group

Other drugs for the treatment of nervous system diseases

Pharmacological Action

Selective transthyretin stabilizer. Tafamidis binds with negative cooperativity to the two thyroxine-binding sites of transthyretin in its native (tetrameric) form, which prevents the dissociation of the complex into monomers and slows amyloidogenesis. The inhibition of dissociation of tetrameric forms of transthyretin justifies the use of tafamidis to slow the progression of transthyretin amyloidosis, primarily hereditary transthyretin-mediated amyloid polyneuropathy.

Pharmacokinetics

After a single oral dose of 20 mg tafamidis taken on an empty stomach, the C_max in plasma was reached after 1.75 hours. Concurrent food intake reduces the rate, but not the extent, of absorption.

Tafamidis is highly bound to plasma proteins (99.9%), primarily to transthyretin. The observed equilibrium V_d is 25.7 L. When tafamidis was administered at doses of 15, 30, or 60 mg once daily for 14 days, the C_max and AUC values increased proportionally to the dose in the range from 15 to 30 mg and increased less intensively than the dose increase in the range from 30 to 60 mg.

Steady-state was reached by day 14 of tafamidis administration at a dose of 20 mg once daily. The C_max^ss and C_min^ss values were 2.7 and 1.6 mcg/mL, respectively.

Based on the results of preclinical studies, it is assumed that tafamidis metabolism occurs via glucuronidation followed by biliary excretion. Approximately 59% of the total administered dose is excreted via the intestine, predominantly unchanged, and about 22% is excreted by the kidneys, mainly as a glucuronidated metabolite.

When tafamidis was administered at a dose of 20 mg once daily for 14 days, the mean T_1/2 at steady state in healthy subjects was 59 hours, and the mean total clearance was 0.42 L/h. After multiple doses of tafamidis 20 mg, the mean T_1/2 and oral clearance were similar to those recorded after a single dose, indicating no induction or inhibition of tafamidis metabolism.

Indications

Treatment of transthyretin amyloidosis in adults with clinically manifest polyneuropathy to delay the development of peripheral nerve impairments.

ICD codes

Dosage Regimen

Administer orally. Take one 61 mg capsule once daily. This constitutes the recommended daily dose.

Ingest the capsule whole with water. Do not chew, crush, or open the capsule.

Take Vindamex with or without food. Food intake does not affect the overall extent of absorption.

Adhere strictly to the once-daily dosing schedule. For optimal results, take the capsule at approximately the same time each day.

If a dose is missed, take it as soon as remembered on the same day. If a full day has passed, skip the missed dose and resume the usual schedule. Do not take a double dose to compensate for a missed one.

No dose adjustment is required for patients with mild to moderate renal impairment or mild to moderate hepatic impairment.

Use with caution in patients with severe hepatic impairment. The safety and efficacy in patients with severe renal impairment (CrCl <30 mL/min) have not been established.

No dose adjustment is necessary for elderly patients.

Adverse Reactions

Digestive system disorders very common – diarrhea, upper abdominal pain.

Urinary system disorders very common – urinary tract infection.

Reproductive system disorders very common – vaginal infection.

Contraindications

Hypersensitivity to tafamidis; pregnancy, breastfeeding period; congenital fructose intolerance; age under 18 years.

Use in Pregnancy and Lactation

The use of tafamidis is not recommended during pregnancy, in women of childbearing potential not using contraception, as well as during lactation.

Use in Hepatic Impairment

No dose adjustment is required in patients with mild or moderate hepatic impairment. Tafamidis should be used with caution in patients with severe hepatic impairment.

Use in Renal Impairment

No dose adjustment is required in patients with mild or moderate renal impairment. Data on the use of the drug in patients with severe renal impairment (CrCl <30 mL/min) are not available.

Pediatric Use

Tafamidis is not used in children because transthyretin amyloid polyneuropathy does not occur in this patient group.

Geriatric Use

No dose adjustment of the drug is required in elderly patients.

Special Precautions

Tafamidis should be used with caution in patients with severe hepatic impairment.

Drug Interactions

In vitro studies, Tafamidis inhibits the breast cancer resistance protein (BCRP) efflux transporter and may increase the systemic exposure of substrates of this transporter (e.g., methotrexate, rosuvastatin, and imatinib).

Tafamidis inhibits the activity of organic anion transporters OAT1 and OAT3. When present in the body at clinically significant concentrations, Tafamidis may interact with substrates of these transporters (e.g., NSAIDs, bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, and zalcitabine).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.