Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
In phase 3 clinical trials with doravirine plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), the most frequently reported adverse reactions were nausea (4 %) and headache (3 %).

Tabulated summary of adverse reactions
The adverse reactions with doravirine plus 2 NRTIs from Phase 3 clinical trials (DRIVE FORWARD, DRIVE SHIFT and DRIVE AHEAD) and postmarketing experience are listed below by body system organ class and frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 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), or not known (cannot be estimated from the available data).

Table 2: Tabulated summary of adverse reactions associated with doravirine used in combination with other antiretrovirals

Frequency                                              Adverse reactions Infections and infestations
Rare                                                   rash pustular
Metabolism and nutrition disorders

Frequency                                                        Adverse reactions Uncommon                                                         hypophosphataemia Rare                                                             hypomagnesaemia Psychiatric disorders
Common                                                           abnormal dreams, insomnia1 Uncommon                                                         nightmare, depression2, anxiety3, irritability, confusional state, suicidal ideation
Rare                                                             aggression, hallucination, adjustment disorder, mood altered, somnambulism
Nervous system disorders
Common                                                           headache, dizziness, somnolence Uncommon                                                         disturbance in attention, memory impairment, paraesthesia, hypertonia, poor quality sleep
Vascular disorders
Uncommon                                       hypertension
Respiratory, thoracic and mediastinal disorders
Rare                                           dyspnoea, tonsillar hypertrophy Gastrointestinal disorders
Common                                         nausea, diarrhoea, flatulence, abdominal pain4, vomiting
Uncommon                                       constipation, abdominal discomfort5, abdominal distension, dyspepsia, faeces soft6,
gastrointestinal motility disorder7
Rare                                           rectal tenesmus
Skin and subcutaneous tissue disorders
Common                                         rash8
Uncommon                                       pruritus
Rare                                           dermatitis allergic, rosacea Not known                                      toxic epidermal necrolysis Musculoskeletal and connective tissue disorders
Uncommon                                       myalgia, arthralgia
Rare                                           musculoskeletal pain
Renal and urinary disorders
Rare                                           acute kidney injury, renal disorder, calculus urinary, nephrolithiasis
General disorders and administration site conditions
Common                                         fatigue
Uncommon                                       asthenia, malaise
Rare                                           chest pain, chills, pain, thirst Investigations
Common                                         alanine aminotransferase increased9 Uncommon                                       lipase increased, aspartate aminotransferase increased, amylase increased, haemoglobin decreased
Rare                                           blood creatine phosphokinase increased 1insomnia  includes: insomnia, initial insomnia and sleep disorder
2depression  includes: depression, depressed mood, major depression, and persistent depressive disorder
3anxiety includes: anxiety and generalised anxiety disorder

4abdominal pain includes: abdominal pain, and abdominal pain upper

5abdominal discomfort includes: abdominal discomfort, and epigastric discomfort 
6faeces soft includes: faeces soft and abnormal faeces

7gastrointestinal motility disorder includes: gastrointestinal motility disorder, and frequent bowel movements 8rash includes: rash, rash macular, rash erythematous, rash generalised, rash maculo-papular, rash papular, and urticarial 9alanine aminotransferase increased includes: alanine aminotransferase increased and hepatocellular injury 


Description of selected adverse reactions

Immune reactivation syndromeIn HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), such as toxic epidermal necrolysis (TEN), have been reported in association with doravirine-containing treatment regimens (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