TIVICAY Film-coated tablet Ref.[7495] Active ingredients: Dolutegravir

Tivicay should be prescribed by physicians experienced in the management of HIV infection.

Posology

Adults

Patients infected with HIV-1 without documented or clinically suspected resistance to the integrase class

The recommended dose of dolutegravir is 50 mg 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.

Patients infected with HIV-1 with resistance to the integrase class (documented or clinically suspected)

The recommended dose of dolutegravir is 50 mg 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).

Adolescents aged 12 and above, to less than 18 years, and weighing at least 20 kg

In patients infected with HIV-1 without resistance to the integrase class, the recommended dose of dolutegravir is 50 mg once daily. Alternatively, if preferred 25 mg may be taken twice daily (see section 5.2). In the presence of integrase inhibitor resistance, there are insufficient data to recommend a dose for olutegravir in adolescents.

Children aged 6 and above, to less than 12 years, and weighing at least 14 kg

In patients infected with HIV-1 without resistance to the integrase class, the recommended dose ofdolutegravir is determined according to the weight of the child (see Table 1 and section 5.2).

Table 1. Paediatric dose recommendations for film-coated tablets:

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 film-coated tablets:

In the presence of integrase inhibitor resistance, there are insufficient data to recommend a dose for dolutegravir in children.

Dispersible Tablets

Tivicay is available as film-coated tablets for patients aged 6 years and above and weighing at least 14 kg. Tivicay is also 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. Patients can change between film-coated tablets and dispersible tablets. However, the bioavailability of film-coated tablets and dispersible 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 film-coated tablets is 50 mg versus 30 mg for dispersible tablets. Patients changing between film-coated and dispersible tablets should follow the dosing recommendations that are specific for the formulation.

Missed doses

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.

Elderly

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).

Renal impairment

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).

Hepatic impairment

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).

Paediatric population

Dolutegravir is also available in dispersible tablets for children aged 4 weeks and above and weighing at least 3 kg. However, the safety and efficacy of dolutegravir in children aged less than 4 weeks or weighing less than 3 kg have not yet been established. In the presence of integrase inhibitor resistance, there are insufficient data to recommend a dose for dolutegravir in children and adolescents. Currently available data are described in section 4.8, 5.1 and 5.2, but no recommendation on a posology can be made.

Method of administration

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).

To reduce the risk of choking, patients should not swallow more than one tablet at a time, and where possible, children weighing 14 to less than 20 kg should preferentially take the dispersible tablet formulation.

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.

Shelf life

Tivicay 10 mg film-coated tablets: 5 years.

Tivicay 25 mg film-coated tablets: 4 years.

Tivicay 50 mg film-coated tablets: 5 years.

Tivicay 10 mg film-coated tablets: 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.

Tivicay 25 mg and 50 mg film-coated tablets: This medicinal product does not require any special storage conditions. 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 30 or 90 film-coated tablets.

Tivicay 10 mg film-coated tablets: Each bottle contains a desiccant.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.