REYATAZ Hard capsule Ref.[6232] Active ingredients: Atazanavir

Therapy should be initiated by a physician experienced in the management of HIV infection.

Posology

Adults

The recommended dose of REYATAZ capsules is 300 mg once daily taken with ritonavir 100 mg once daily and with food. Ritonavir is used as a booster of atazanavir pharmacokinetics (see sections 4.5 and 5.1). (See also section 4.4 Withdrawal of ritonavir only under restrictive conditions).

Paediatric patients (6 years to less than 18 years of age and weighing at least 15 kg)

The dose of atazanavir capsules for paediatric patients is based on body weight as shown in Table 1 and should not exceed the recommended adult dose. REYATAZ capsules must be taken with ritonavir and have to be taken with food.

Table 1. Dose for paediatric patients (6 years to less than 18 years of age and weighing at least 15 kg) for REYATAZ capsules with ritonavir:

^a Ritonavir capsules, tablets or oral solution.

Paediatric patients (at least 3 months of age and weighing at least 5 kg)

REYATAZ oral powder is available for paediatric patients at least 3 months of age and weighing at least 5 kg (see Summary of Product Characteristics for REYATAZ oral powder). Switching to REYATAZ capsules from REYATAZ oral powder is encouraged as soon as patients are able to consistently swallow capsules.

When transitioning between formulations, a change in dose may be needed. Consult the dosing table for the specific formulation (see Summary of Product Characteristics for REYATAZ oral powder).

Special populations

Renal impairment

No dosage adjustment is needed. REYATAZ with ritonavir is not recommended in patients undergoing haemodialysis (see sections 4.4 and 5.2).

Hepatic impairment

REYATAZ with ritonavir has not been studied in patients with hepatic impairment. REYATAZ with ritonavir should be used with caution in patients with mild hepatic impairment. REYATAZ with ritonavir must not be used in patients with moderate to severe hepatic impairment (see sections 4.3, 4.4 and 5.2).

In case of withdrawal of ritonavir from the initial recommended ritonavir boosted regimen (see section 4.4), unboosted REYATAZ could be maintained in patients with mild hepatic impairment at a dose of 400 mg, and in patients with moderate hepatic impairment with a reduced dose of 300 mg once daily with food (see section 5.2). Unboosted REYATAZ must not be used in patients with severe hepatic impairment.

Pregnancy and Postpartum

During the second and third trimesters of pregnancy:

REYATAZ 300 mg with ritonavir 100 mg may not provide sufficient exposure to atazanavir, especially when the activity of atazanavir or the whole regimen may be compromised due to drug resistance. Since there are limited data available and due to inter-patient variability during pregnancy, Therapeutic Drug Monitoring (TDM) may be considered to ensure adequate exposure.

The risk of a further decrease in atazanavir exposure is expected when atazanavir is given with medicinal products known to reduce its exposure (e.g. tenofovir disoproxil or H₂-receptor antagonists).

• If tenofovir disoproxil or an H₂-receptor antagonist is needed, a dose increase to REYATAZ 400 mg with ritonavir 100 mg with TDM may be considered (see sections 4.6 and 5.2).
• It is not recommended to use REYATAZ with ritonavir for pregnant patients who are receiving both tenofovir disoproxil and an H₂-receptor antagonist. (See section 4.4 Withdrawal of ritonavir only under restrictive conditions).

During postpartum:

Following a possible decrease in atazanavir exposure during the second and third trimester, atazanavir exposures might increase during the first two months after delivery (see section 5.2). Therefore, postpartum patients should be closely monitored for adverse reactions.

• During this time, postpartum patients should follow the same dose recommendation as for nonpregnant patients, including those for co-administration of medicinal products known to affect atazanavir exposure (see section 4.5).

Paediatric patients (less than 3 months of age)

REYATAZ should not be used in children less than 3 months because of safety concerns especially taking into account the potential risk of kernicterus.

Method of administration

For oral use. The capsules should be swallowed whole.

Human experience of acute overdose with REYATAZ is limited. Single doses up to 1,200 mg have been taken by healthy volunteers without symptomatic untoward effects. At high doses that lead to high drug exposures, jaundice due to indirect (unconjugated) hyperbilirubinaemia (without associated liver function test changes) or PR interval prolongations may be observed (see sections 4.4 and 4.8).

Treatment of overdose with REYATAZ should consist of general supportive measures, including monitoring of vital signs and electrocardiogram (ECG), and observations of the patient’s clinical status. If indicated, elimination of unabsorbed atazanavir should be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid removal of unabsorbed drug. There is no specific antidote for overdose with REYATAZ. Since atazanavir is extensively metabolised by the liver and is highly protein bound, dialysis is unlikely to be beneficial in significant removal of this medicinal product.

2 years.

Do not store above 25°C.

REYATAZ 100 mg hard capsules: Each carton contains one high-density polyethylene (HDPE) bottle closed with child-resistant polypropylene closure. Each bottle contains 60 hard capsules.

Each carton contains 60 × 1 capsules; 10 blister cards of 6 × 1 capsules each in Alu/Alu perforated unit dose blisters.

REYATAZ 150 mg hard capsules: Each carton contains one high-density polyethylene (HDPE) bottle closed with child-resistant polypropylene closure. Each bottle contains 60 hard capsules.

Each carton contains 60 × 1 capsules; 10 blister cards of 6 × 1 capsules each in Alu/Alu perforated unit dose blisters.

REYATAZ 200 mg hard capsules: Each carton contains one high-density polyethylene (HDPE) bottle or three high-density polyethylene (HDPE) bottles closed with child-resistant polypropylene closure. Each bottle contains 60 hard capsules.

Each carton contains 60 × 1 capsules; 10 blister cards of 6 × 1 capsules each in Alu/Alu perforated unit dose blisters.

REYATAZ 300 mg hard capsules: Each carton contains one high-density polyethylene (HDPE) bottle or three high-density polyethylene (HDPE) bottles closed with child-resistant polypropylene closure. Each bottle contains 30 hard capsules.

Each carton contains 30 × 1 capsules; 5 blister cards of 6 × 1 capsules each in Alu/Alu perforated unit dose blisters.

Not all pack sizes may be marketed.

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