Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions with Juluca (from clinical studies – see section 5.1) were diarrhoea (2%) and headache (2%).

The most severe adverse reaction, related to the treatment with dolutegravir (from pooled Phase IIb and Phase III clinical studies), seen in an individual patient, was a hypersensitivity reaction that included rash and severe liver effects (see section 4.4).

Tabulated list of adverse reactions

The sources of information for the safety database include 2 identical, randomised, open-label studies SWORD-1 and SWORD-2 (see section 5.1), pooled studies from individual components and post-marketing experience.

The adverse reactions considered at least possibly related to treatment with the components of Juluca from clinical studies and post-marketing experience are listed in Table 2 by body system, organ class and frequency. Frequencies are defined as very common (1/10), common (1/100 to <1/10), uncommon (1/1 000 to <1/100), rare (1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data).

Table 2:      Tabulated list of adverse reactions to Juluca based on clinical study and post- marketing experience with Juluca and its individual components

System organ class         Frequency          Adverse drug reactions
(SOC)                      category*
Blood and lymphatic        common             decreased white blood cell count systems disorders: decreased haemoglobin
 decreased platelet count
Immune system              uncommon           hypersensitivity (see section 4.4) disorders                  not known          immune reconstitution syndrome Metabolism and             very common        increased total cholesterol (fasted) nutrition disorders increased LDL cholesterol (fasted) common             decreased appetite
 increased triglycerides (fasted)
Psychiatric disorders      very common        insomnia common             abnormal dreams
 depression sleep disorders
 depressed mood
 anxiety uncommon           suicidal ideation or suicide attempt (particularly in patients with a pre-existing history of depression or psychiatric illness), panic attack

rare              completed suicide (particularly in patients with a pre- existing history of depression or psychiatric illness)
Nervous system            very common       headache disorders dizziness common            somnolence
Gastrointestinal          very common       nausea disorders increased pancreatic amylase
 diarrhoea common            abdominal pain
 vomiting flatulence
 increased lipase
 abdominal discomfort upper abdominal pain
 dry mouth
Hepatobiliary             very common       increased transaminases disorders                                   (alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations) common            increased bilirubin uncommon          hepatitis rare              acute hepatic failure**
Skin and subcutaneous     common            rash tissue disorders pruritus
Musculoskeletal and       uncommon          arthralgia connective tissue disorders                                   myalgia
General disorders and     common            fatigue administration site conditions
Investigations            common            creatine phosphokinase (CPK) elevations, weight increased

*     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 or rilpivirine have been associated with increases in serum creatinine occurring 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 dolutegravir/rilpivirine and remained stable through 148 weeks. A mean change from baseline of 9.86 mol/L (SD 10.4 mol/L) was observed after 148 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.

Metabolic parameters

Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 4.4).
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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il

Additionally, you should also report to GSK Israel (il.safety@gsk.com).