isorders
depressed mood
anxiety
uncommon
suicidal ideation or suicide attempt (particularly in patients with a pre-existing history of depression or psychiatric illness)
Nervous system disorders
very common
headache
dizziness
common
somnolence
Gastrointestinal disorders
very common
nausea
increased pancreatic amylase
diarrhoea
common
abdominal pain
vomiting
flatulence
increased lipase
abdominal discomfort
upper abdominal pain
dry mouth
Hepatobiliary disorders
very common
increased transaminases
(alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations)
common
increased bilirubin
uncommon
hepatitis
rare
acute hepatic failure**
Skin and subcutaneous tissue disorders
common
rash
pruritus
Musculoskeletal and connective tissue disorders
uncommon
arthralgia
myalgia
General disorders and administration site conditions
common
fatigue
Investigations
common
creatine phosphokinase (CPK) elevations
* Frequencies are assigned based on the maximum frequencies observed in the pooled SWORD studies or studies with the individual components
** This adverse reaction was identified through post-marketing surveillance for dolutegravir in combination with other ARVs. The frequency category of rare was estimated based on post-marketing reports.
Description of selected adverse reactions
Changes in laboratory biochemistries
Dolutegravir and rilpivirine have been associated with increases in serum creatinine occuring in the first week of treatment when administered with other antiretroviral medicinal products. Increases in serum creatinine occurred within the first four weeks of treatment with Juluca and remained stable through 48 weeks. A mean change from baseline of 8.22 μmol/L (range -26.5 to 51.2 μmol/L) was observed after 48 weeks treatment. These changes are related to inhibition of active transport, and are not considered to be clinically relevant as they do not reflect a change in glomerular filtration rate.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: http://www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
No specific symptoms or signs have been identified following acute overdose with dolutegravir or rilpivirine 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 Juluca. If overdose occurs, the patient should be treated supportively with appropriate monitoring, including monitoring of vital signs and ECG (QT interval), as necessary. As dolutegravir and rilpivirine are highly bound to plasma proteins, dialysis is unlikely to result in significant removal of the active substances.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antivirals for systemic use, antivirals for treatment of HIV infections, combinations. ATC code: J05AR21
Mechanism of action
Dolutegravir inhibits HIV integrase by binding to th |
