Pifeltro

Therapy should be initiated by a physician experienced in the management of HIV infection. Posology The recommended dose is one 100 mg tablet taken orally once daily with or without food. 5). Co-administration of doravirine with other moderate CYP3A inducers has not been evaluated, but decreased doravirine concentrations are expected.

, dabrafenib, lesinurad, bosentan, thioridazine, nafcillin, modafinil, telotristat ethyl) cannot be avoided, one 100 mg tablet of Pifeltro should be taken twice daily (approximately 12 hours apart). Missed dose If the patient misses a dose of Pifeltro within 12 hours of the time it is usually taken, the patient should take as soon as possible and resume the normal dosing schedule.

If a patient misses a dose by more than 12 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not take 2 doses at one time. 2). Renal impairment No dose adjustment of doravirine is required in patients with mild, moderate, or severe renal impairment.

2). Hepatic impairment No dose adjustment of doravirine is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Doravirine has not been studied in patients with severe hepatic impairment (Child-Pugh Class C).

It is not known whether the exposure to doravirine will increase in patients with severe hepatic impairment. 2). Paediatric population Safety and efficacy of Pifeltro in children aged less than 12 years or weighing less than 35 kg have not been established.

No data are available. 2).

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 14 Frequency Adverse reactions Metabolism and nutrition disorders 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 Hepatobiliary disorders Not known hepatitis 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 15 Frequency Adverse reactions 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 syndrome In 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.

NNRTI substitutions and use of doravirine Doravirine has not been evaluated in patients with previous virologic failure to any other antiretroviral therapy. NNRTI-associated mutations detected at screening were part of exclusion criteria in the Phase 2b/3-studies.

1). There is not sufficient clinical evidence to support the use of doravirine in patients infected with HIV-1 with evidence of resistance to the NNRTI class. 8). At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions.

If signs and symptoms suggestive of 4 these reactions appear, doravirine-containing regimens should be withdrawn immediately and an alternative treatment considered (as appropriate). Clinical status should be closely monitored, and appropriate therapy should be initiated.

If the patient has developed a serious reaction such as TEN, with the use of doravirine-containing regimens, treatment with doravirine-containing regimens must not be restarted in this patient at any time. 5). Immune reactivation syndrome Immune reactivation syndrome has been reported in patients treated with combination antiretroviral therapy.

During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, autoimmune hepatitis, polymyositis, and Guillain- Barré syndrome) have also been reported to occur in the setting of immune reactivation; however, the time to onset is more variable and can occur many months after initiation of treatment.

Lactose The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

1. 5). These medicinal products include, but are not limited, to the following: • carbamazepine, oxcarbazepine, phenobarbital, phenytoin • rifampicin, rifapentine • St. John’s wort (Hypericum perforatum) • mitotane • enzalutamide • lumacaftor