Delstrigo

Therapy should be initiated by a physician experienced in the management of HIV infection. Posology The recommended dose of Delstrigo is one 100/300/245 mg tablet taken orally once daily with or without food. Dose adjustment If Delstrigo is co-administered with rifabutin, the doravirine dose should be increased to 100 mg twice daily.

5). Co-administration of doravirine with other moderate CYP3A inducers has not been evaluated, but decreased doravirine concentrations are expected. 5). 3 Missed dose If the patient misses a dose of Delstrigo within 12 hours of the time it is usually taken, the patient should take Delstrigo as soon as possible and resume the normal dosing schedule.

If a patient misses a dose of Delstrigo 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. Special populations Elderly There are limited data available on the use of doravirine, lamivudine, and tenofovir disoproxil in patients aged 65 years and over.

2). 4). Renal impairment No dose adjustment of Delstrigo is required in patients with estimated creatinine clearance (CrCl) ≥ 50 mL/min. 2). 4). 2). Hepatic impairment No dose adjustment of doravirine/lamivudine/tenofovir disoproxil 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 Delstrigo 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 post-marketing 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), very rare (< 1/10 000), or not known (cannot be estimated from the available data).

Table 2:

Tabulated summary of adverse reactions associated with doravirine/lamivudine/tenofovir disoproxil Frequency Adverse reactions Infections and infestations Rare rash pustular Blood and lymphatic systems disorders Uncommon neutropenia*, anaemia*, thrombocytopenia* Very rare pure red cell aplasia* Metabolism and nutrition disorders Uncommon hypophosphataemia, hypokalaemia* Rare hypomagnesaemia, lactic acidosis* 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 Very rare peripheral neuropathy (or paraesthesia)* Vascular disorders Uncommon hypertension Respiratory, thoracic and mediastinal disorders Common cough*, nasal symptoms* Rare dyspnoea, tonsillar hypertrophy Gastrointestinal disorders Common nausea, diarrhoea, abdominal pain4, vomiting, flatulence Uncommon constipation, abdominal discomfort5, abdominal distension, dyspepsia, faeces soft6, gastrointestinal motility disorder7, pancreatitis* Rare rectal tenesmus Hepatobiliary disorders Rare hepatic steatosis*, hepatitis† 18 Frequency Adverse reactions Skin and subcutaneous tissue disorders Common alopecia*, rash8 Uncommon pruritus Rare dermatitis allergic, rosacea, angioedema* Not known toxic epidermal necrolysis Musculoskeletal and connective tissue disorders Common muscle disorders*, bone mineral density decreased* Uncommon myalgia, arthralgia, rhabdomyolysis*‡, muscular weakness*‡ Rare musculoskeletal pain, osteomalacia (manifested as bone pain and infrequently contributing to fractures)*, myopathy* Renal and urinary disorders Uncommon increased creatinine*, proximal renal tubulopathy (including Fanconi syndrome)* Rare acute kidney injury, renal disorder, calculus urinary, nephrolithiasis, acute renal failure*, renal failure*, acute tubular necrosis*, nephritis (including acute interstitial)*, nephrogenic diabetes insipidus* General disorders and administration site conditions Common fatigue, fever* Uncommon asthenia, malaise Rare chest pain, chills, pain, thirst Investigations Common alanine aminotransferase increased9 Uncommon aspartate aminotransferase increased, lipase increased, amylase increased, haemoglobin decreased Rare blood creatine phosphokinase increased *This adverse reaction was not identified as an adverse reaction associated with doravirine from the Phase 3 clinical studies (DRIVE-FORWARD, DRIVE-AHEAD, DRIVE-SHIFT), but is included in this table as an adverse reaction based on the Summary of Product Characteristics (SmPC) of 3TC and/or TDF.

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 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. Severe acute exacerbation of hepatitis B in patients co-infected with HIV-1 and HBV All patients with HIV-1 should be tested for the presence of hepatitis B virus (HBV) before initiating antiretroviral therapy.

, liver decompensated and liver failure) have been reported in patients who are co-infected with HIV-1 and HBV, and have discontinued lamivudine or tenofovir disoproxil, two of the components of Delstrigo. Patients who are co-infected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with Delstrigo.

If appropriate, initiation of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

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 4