Generiek versus merk LT4 bij kinderen

[laura]

Generic and Brand-Name l-Thyroxine Are Not Bioequivalent for Children With Severe Congenital Hypothyroidism

Abstract

Context:
In the United States, generic substitution of levothyroxine (l-T4) by pharmacists is permitted if the formulations are deemed to be bioequivalent by the Federal Drug Administration, but there is widespread concern that the pharmacokinetic standard used is too insensitive.

Objective:
We aimed to evaluate the bioequivalence of a brand-name l-T4 (Synthroid) and an AB-rated generic formulation (Sandoz, Princeton, NJ) in children with severe hypothyroidism.

Design:
This was a prospective randomized crossover study in which patients received 8 weeks of one l-T4 formulation followed by 8 weeks of the other.

Setting:
The setting was an academic medical center.

Patients:
Of 31 children with an initial serum TSH concentration >100 mU/L, 20 had congenital hypothyroidism (CH), and 11 had autoimmune thyroiditis.

Main Outcome Measures:
The primary endpoint was the serum TSH concentration. Secondary endpoints were the free T4 and total T3 concentrations.

Results:
The serum TSH concentration was significantly lower after 8 weeks of Synthroid than after generic drug (P = .002), but thyroid hormone levels did not differ significantly. Subgroup analysis revealed that the difference in TSH was restricted to patients with CH (P = .0005). Patients with CH required a higher l-T4 dose (P < .0004) and were younger (P = .003) but were not resistant to thyroid hormone; 15 of 16 CH patients had severe thyroid dysgenesis or agenesis on imaging. The response to generic vs brand-name preparation remained significant when adjusted for age.

Conclusions:
Synthroid and an AB-rated generic l-T4 are not bioequivalent for patients with severe hypothyroidism due to CH, probably because of diminished thyroid reserve. It would therefore seem prudent not to substitute l-T4 formulations in patients with severe CH, particularly in those <3 yr of age. Our results may have important implications for other severely hypothyroid patients in whom precise titration of l-T4 is necessary.

[Ber]

Zeker in interessant stuk om te lezen. Was er al alert op dat we bij de apotheek steeds thyrax krijgen, maar zal dit zeker goed in de gaten blijven houden.