Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands
Tivicay is indicated in combination with other anti-retroviral medicinal products for the treatment of Human Immunodeficiency Virus (HIV) infected adults, adolescents and children of at least 4 weeks of age or older and weighing at least 3 kg.
Tivicay should be prescribed by physicians experienced in the management of HIV infection.
The recommended dose of dolutegravir is 30 mg (six 5 mg dispersible tablets) orally once daily.
Dolutegravir should be administered twice daily in this population when co-administered with some medicines (e.g. efavirenz, nevirapine, tipranavir/ritonavir, or rifampicin). Please refer to section 4.5.
The recommended dose of dolutegravir is 30 mg (six 5 mg dispersible tablets) twice daily.
In the presence of documented resistance that includes Q148 + ≥2 secondary mutations from G140A/C/S, E138A/K/T, L74I, modelling suggests that an increased dose may be considered for patients with limited treatment options (less than 2 active agents) due to advanced multi class resistance (see section 5.2).
The decision to use dolutegravir for such patients should be informed by the integrase resistance pattern (see section 5.1).
The recommended dose of dolutegravir is determined according to weight and age (see Table 1 and section 5.2).
Table 1. Paediatric dose recommendations for dispersible tablets:
| Body weight (kg) | Dose |
|---|---|
| 3 to less than 6 | 5 mg once daily |
| 6 to less than 10 <6 months ≥6 months | 10 mg once daily 15 mg once daily |
| 10 to less than 14 | 20 mg once daily |
| 14 to less than 20 | 25 mg once daily |
| 20 or greater | 30 mg once daily |
Alternatively, if preferred the dose may be divided equally into 2 doses, with one dose taken in the morning and one dose taken in the evening (see Table 2 and section 5.2).
Table 2. Alternative paediatric dose recommendations for dispersible tablets:
| Body weight (kg) | Dose |
|---|---|
| 3 to less than 6 | --- |
| 6 to less than 10 <6 months ≥6 months | 5 mg twice daily 10 mg twice daily |
| 10 to less than 14 | 10 mg twice daily |
| 14 to less than 20 | 15 mg twice daily |
| 20 or greater | 15 mg twice daily |
There are insufficient data to recommend a dose for dolutegravir in integrase inhibitor resistant adolescents, children and infants.
Tivicay is available as dispersible tablets for patients aged 4 weeks and above and weighing at least 3 kg, or for patients in whom film-coated tablets are not appropriate. Tivicay is available as film-coated tablets for patients aged 6 years and above and weighing at least 14 kg. Patients can change between dispersible tablets and film-coated tablets. However, the bioavailability of dispersible tablets and film-coated tablets is not comparable, therefore they are not interchangeable on a milligram per milligram basis (see section 5.2). For example, the recommended adult dose for dispersible tablets is 30 mg versus 50 mg for film-coated tablets. Patients changing between dispersible and film-coated tablets should follow the dosing recommendations that are specific for the formulation.
If the patient misses a dose of Tivicay, the patient should take Tivicay as soon as possible, providing the next dose is not due within 4 hours. If the next dose is due within 4 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
There are limited data available on the use of dolutegravir in patients aged 65 years and over. There is no evidence that elderly patients require a different dose than younger adult patients (see section 5.2).
No dosage adjustment is required in patients with mild, moderate or severe (CrCl <30 mL/min, not on dialysis) renal impairment. No data are available in subjects receiving dialysis although differences in pharmacokinetics are not expected in this population (see section 5.2).
No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh grade A or B). No data are available in patients with severe hepatic impairment (Child-Pugh grade C); therefore dolutegravir should be used with caution in these patients (see section 5.2).
The safety and efficacy of dolutegravir in children aged less than 4 weeks or weighing less than 3 kg have not yet been established. There are insufficient data to recommend a dose for dolutegravir in integrase inhibitor resistant adolescents, children and infants. Currently available data are described in section 4.8, 5.1 and 5.2, but no recommendation on a posology can be made.
Oral use.
Tivicay can be taken with or without food (see section 5.2). In the presence of integrase class resistance, Tivicay should preferably be taken with food to enhance exposure (particularly in patients with Q148 mutations) (see section 5.2). The dispersible tablets may be dispersed in drinking water, or swallowed whole with drinking water.
When dispersed, the amount of water will depend on the number of tablets prescribed. The tablet(s) should be fully dispersed before swallowing. However, tablets should not be chewed, cut or crushed. The dose of medicine must be given within 30 minutes of preparation. If it has been more than 30 minutes the dose should be washed away and a new dose should be prepared. Comprehensive instructions for dispersing the tablet are provided in the package leaflet (see Step-by-step instructions for use).
If swallowing tablets whole, patients should not swallow more than one tablet at a time, to reduce the risk of choking.
There is currently limited experience with overdosage in dolutegravir.
Limited experience of single higher doses (up to 250 mg in healthy subjects) revealed no specific symptoms or signs, apart from those listed as adverse reactions.
Further management should be as clinically indicated or as recommended by the national poisons centre, where available. There is no specific treatment for an overdose of dolutegravir. If overdose occurs, the patient should be treated supportively with appropriate monitoring, as necessary. As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.
3 years.
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not remove the desiccant. Do not swallow the desiccant. This medicinal product does not require any special temperature storage conditions.
HDPE (high density polyethylene) bottles closed with child resistant polypropylene screw closures, with a polyethylene faced induction heat seal liner. The bottles contain 60 dispersible tablets and a desiccant.
A dosing cup and oral syringe, both made from polypropylene with graduation marks, are supplied with the pack. The syringe’s plunger is made from HDPE.
Comprehensive instructions for dispersing the tablet are provided in the package leaflet (see Step-by-step instructions for use).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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