FDA approves dolutegravir formulations to treat infants and young children

On 12 June 2020 the US Food and Drug Administration (FDA) approval dolutegravir (Tivicay) tablets and dolutegravir tablets for oral suspension (Tivicay PD) for infants and children in combination with other antiretrovirals.

Approval was granted to the originator manufacturer, ViiV Healthcare. The new formulations are indicated for paediatric patients at least 4 weeks old and weighing at least 3 kg who are ART-naive or ART-experienced but have not previously received an integrase strand transferase inhibitor (INSTI).

The safety and pharmacokinetics (PK) of the two formulations in this weight-band/age group were evaluated in the IMPAACT P1093 trial and two weight-band-based PK substudies of the PENTA ODYSSEY trial.

Overall, the safety data in these paediatric studies were similar to those in adults and there was no clinically significant difference in dolutegravir exposure.

IMPAACT P1093 is an ongoing, multicentre, open-label, non-comparative trial of paediatric participants aged 4 weeks to less than 18 years.

The safety analysis – based on week 24 data in 75 participants with a median age of 27 months – found 11% experienced drug-related clinical adverse events. Grade 1 to 2 drug-related IRIS was reported in two participants. No Grade 3 or 4 drug-related adverse events were reported. No participants discontinued due to adverse events.

The dolutegravir tablets for oral suspension are 5 mg dispersible: weight-based dosage for infants and young children aged 4 weeks and older at weighing at least 3 kg is shown in Table 1.

Table 1: Recommended weight-based dosage for dolutegravir tablets for oral suspension

The 5 mg tablets must be dispersed in 5 mL of drinking water (if using 1 or 3 tablets) or 10 mL (if using 4, 5, or 6 tablets) and the oral suspension administered within 30 minutes of mixing.

Alternatively, paediatric patients weighing 14 kg or more can receive dolutegravir oral 10 mg or 50 mg tablets (although the tablets for oral suspension are preferred in those weighing less than 20 mg). The dosages are 40 mg (4 x 10 mg tablets) and 50 mg (1 x 50 mg adult tablet) for the 14 to 20 kg and 20 kg and above weight-bands respectively. The 10 mg and 50 mg tablets cannot be crushed, cut, chewed or dispersed.

The label includes a warning that dolutegravir 10 mg tablets and 5 mg tablets for oral suspension are not bioequivalent (tablets for oral suspension approximately 1.6-fold that of oral tablets) so cannot be interchanged on a milligram-per-milligram basis and to follow the respective recommended dosing.

This application received priority review designation (usually within six months).

comments

This approval represents a welcome addition to the treatment of infants and young children with HIV and an excellent collaboration between the IMPAACT and PENTA networks.

A generic 10 mg scored, dispersible formulation of dolutegravir, to simplify weight-band dosing, is currently under review by the FDA (with approval expected by the end of the year) and another version close behind.

Body weight	Once-daily dose*	Number of tablets
3 kg to less than 6 kg	5 mg	1
6 kg to less than 10 kg	15 mg	3
10 kg to less than 14 kg	20 mg	4
14 kg to less than 20 kg	25 mg	5
20 kg and greater	30 mg	6