verse development outcomes, including neural tube defects, were identified (see section 5.3). Dolutegravir was shown to cross the placenta in animals.
Animal studies with rilpivirine do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
Lower exposures of dolutegravir and rilpivirine were observed during pregnancy (see sections 4.2, 4.4, 5.1, 5.2).
The use of Juluca during pregnancy is not recommended.
Breast-feeding
It is unknown whether dolutegravir or rilpivirine are excreted in human milk. Available toxicological data in animals has shown excretion of dolutegravir and rilpivirine in milk. In lactating rats that received a single oral dose of dolutegravir 50 mg/kg at 10 days postpartum, dolutegravir was detected in milk at concentrations typically higher than blood. It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Fertility
There are no data on the effects of dolutegravir or rilpivirine on human male or female fertility. Animal studies indicate no clinically relevant effects on male or female fertility (see section 5.3).
4.7 Effects on ability to drive and use machines
Patients should be informed that fatigue, dizziness and somnolence have been reported during treatment with the components of Juluca. The clinical status of the patient and the adverse reaction profile of Juluca should be borne in mind when considering the patient's ability to drive or operate machinery.
4.8 Undesirable effects
Summary of the safety profile
Clinical safety data with Juluca is limited. The most frequently reported adverse reactions considered possibly or probably related to the combined administration of dolutegravir plus rilpivirine in 513 HIV-1 infected subjects in the Phase III clinical trials (see section 5.1), were diarrhoea (2%) and headache (2%).
The most severe adverse reaction, possibly related to the treatment with dolutegravir (from pooled from 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 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 summary of adverse reactions to Juluca based on clinical study and post-marketing experience with Juluca and its individual components
System Organ Class (SOC)
Frequency category*
Adverse drug reactions
Blood and lymphatic systems disorders:
common
decreased white blood cell count
decreased haemoglobin
decreased platelet count
Immune system disorders
uncommon
hypersensitivity (see section 4.4)
not known
immune reconstitution syndrome
Metabolism and nutrition disorders
very common
increased total cholesterol (fasted)
increased LDL cholesterol (fasted)
common
decreased appetite
increased triglycerides (fasted)
Psychiatric disorders
very common
insomnia
common
abnormal dreams
depression
sleep d |
