Emtriva 10 mg/ml oral solution

Update to section 4.4 and 4.6 to update wording related to the risk of HIV transmission and the removal of the disease information relating to sexual transmission of HIV and amendment of the sections relating to breast-feeding.

An editorial change has also been made to the SmPC for Emtriva 10 mg/ml oral solution to correct an error in the sodium content.

To update wording in section 2 related to the risk of HIV transmission - removal of the disease information relating to sexual transmission of HIV and amendment of the sections relating to breast-feeding. Also update the contact details of the local representative listed in the Package Leaflet for Estonia, Latvia, Lithuania and Romania. An editorial change has also been made to the for Emtriva 10 mg/ml oral solution to correct an error in the sodium content.

Type 1B variation for Emtriva 10 mg/mL oral solution to update the package information leaflet, labelling  and SmPC in accordance with the release of the Annex to the European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’.

In line with the aforementioned guidance the following wording has been added to section 2 of the PIL, sections 2 and 4.4 of the SmPC  and section 3 of the labeling for the Emtriva oral solution only;

Approval of MA Transfer application changing the Emtriva MA Holder (MAH) from Gilead Sciences International Ltd., Cambridge - UK (GSIL; ‘transferor’) to Gilead Sciences Ireland UC, Cork - Ireland (GSIUC; ‘transferee’) as a result of ‘BREXIT’. The full details of the new MAH is:

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

·         Section 4.4 

o    Revise the HIV class label wording on mitochondrial dysfunction following the review of existing data on mitochondrial toxicity including the Mitochondrial Toxicity in Children (MITOC) Study

o    The PILs were also updated accordingly

·         Update to section 4.4 of the SmPC “Special warnings and precautions for use” to revise the wording regarding the risk of sexual transmission of HIV infection following CHMP request adopted in December 2013.

- Sections 4.4 and 4.8 of the SPC have been updated to include the below wording:

·         “Autoimmune disorders (such as Graves’ disease) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment”

- Additional changes to sections 4.4 and 4.8 are as follows:

• Expression of combination antiretroviral therapy (CART) was amended throughout sections 4.4 and 4.8 of the SPC

Section 10

- Change to date of revision to May 2013

- Section 4.1 – Update to the indication statement ‘Emtriva is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected adults and children aged 4 months and over’

- Section 4.2 – Additional statements for the Posology section - inclusion of paragraphs describing what to do when a dose of Emtriva is missed or when a patient vomits within an hour of taking Emtriva

- Section 4.2- Removal of statement that no data is available on which to make a dosage recommendation in paediatric patients with renal insufficiency

- Section 4.2- Addition of paragraph on dose recommendations in paediatric population......

Paediatric population: The recommended dose of Emtriva for children aged 4 months and over and adolescents up to 18 years of age weighing at least 33 kg who are able to swallow hard capsules is one 200 mg hard capsule, taken orally, once daily.

There are no data regarding the efficacy and only very limited data regarding the safety of emtricitabine in infants below 4 months of age.  Therefore Emtriva is not recommended for use in those aged less than 4 months (for pharmacokinetic data in this age group, see section 5.2).

No data are available on which to make a dose recommendation in paediatric patients with renal insufficiency.

Method of administration

Emtriva 200 mg hard capsules should be taken once daily, orally with or without food.

Emtriva is also available as a 10 mg/ml oral solution for use in infants aged 4 months and over, children and patients who are unable to swallow hard capsules and patients with renal insufficiency.  Please refer to the Summary of Product Characteristics for Emtriva 10 mg/ml oral solution.  Due to a difference in the bioavailability of emtricitabine between the hard capsule and oral solution presentations, 240 mg emtricitabine administered as the oral solution should provide similar plasma levels to those observed after administration of one 200 mg emtricitabine hard capsule (see section 5.2).

- Section 4.4- Co‑administration of other medicinal products- inclusion of the statement that Emtriva should not be taken with any medicinal products containing emtricitabine or lamivudine

- Section 4.4- Inclusion of statements on elderly and paediatric populations..........
 
Elderly: Emtriva has not been studied in patients over the age of 65.  Elderly patients are more likely to have decreased renal function; therefore caution should be exercised when treating elderly patients with Emtriva.

Paediatric population: In addition to the adverse reactions experienced by adults, anaemia and skin discolouration occurred more frequently in clinical trials involving HIV infected paediatric patients (see section 4.8).

- Section 4.6 – Titled ‘Fertility, pregnancy and lactation’ – within this section amendments to the pregnancy, breast-feeding & fertility statements..........

Pregnancy
A moderate amount of data on pregnant women (between 300‑1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine.  Animal studies do not indicate reproductive toxicity.  The use of emtricitabine may be considered during pregnancy, if necessary.

Breast‑feeding

Emtricitabine has been shown to be excreted in human milk.  There is insufficient information on the effects of emtricitabine in newborns/infants.  Therefore Emtriva should not be used during breast-feeding.

As a general rule, it is recommended that HIV infected women do not breast‑feed their infants under any circumstances in order to avoid transmission of HIV to the infant.

Fertility

No human data on the effect of emtricitabine are available.  Animal studies do not indicate harmful effects of emtricitabine on fertility.

- Section 5.1 - Inclusion of statement ‘Paediatric population: There is no clinical experience of the use of emtricitabine in infants less than 4 months of age’

- Section 5.2 – Inclusion of statements on gender, ethnicity and paediatric populations..........

Age: Pharmacokinetic data are not available in the elderly (over 65 years of age). 

Gender: Although the mean C_max and C_min were approximately 20% higher and mean AUC was 16% higher in females compared to males, this difference was not considered clinically significant.

Ethnicity: No clinically important pharmacokinetic difference due to ethnicity has been identified.

Paediatric population: In general, the pharmacokinetics of emtricitabine in infants, children and adolescents (aged 4 months up to 18 years) are similar to those seen in adults.

- Section 10 – Change to the date of revision

Change to Section 10: Date of revision of text on the SPC to September 2008.

MAH post code updated following post office notification