Symtuza

Darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir alafenamide 10 mg

HIV-1 infection in adults & adolescents ≥12 yr w/ body wt at least 40 kg.

Antiretroviral therapy-naïve or -experienced patient 1 tab once daily.

Should be taken with food.

Hypersensitivity. Severe (Child-Pugh Class C) hepatic impairment. Co-administration w/ strong CYP3A inducers eg, carbamazepine, phenobarb, phenytoin, rifampicin, lopinavir/ritonavir, St. John's wort (Hypericum perforatum); alfuzosin; amiodarone, dronedarone, ivabradine, quinidine, ranolazine; colchicine when used in patients w/ renal &/or hepatic impairment; ergot derivatives (eg, dihydroergotamine, ergometrine, ergotamine, methylergonovine); dapoxetine; domperidone; naloxegol; pimozide, quetiapine, sertindole, lurasidone; elbasvir/grazoprevir; triazolam, midazolam administered orally; sildenafil when used for the treatment of pulmonary arterial HTN, avanafil, simvastatin, lovastatin & lomitapide; dabigatran, ticagrelor.

Discontinue immediately if signs or symptoms of severe skin reactions develop. Residual risk of HIV transmission. Should not be used in treatment-experienced patients w/ ≥1 DRV-RAMs or w/ HIV-1 RNA ≥100,000 copies/mL or CD4+ cell count <100 cells x 10⁶/L. Increased risk for liver function abnormalities in patients w/ pre-existing liver dysfunction, including chronic hepatitis B or C. Interrupt or discontinue treatment in case of evidence of new or worsening liver dysfunction. Safety & efficacy in patients co-infected w/ HIV-1 & HCV have not been established. Discontinuation of Symtuza in patients co-infected w/ HIV & HBV may be associated w/ severe acute exacerbations of hepatitis. Reports of mitochondrial dysfunction in HIV -ve infants following exposure in utero &/or postnatally to nucleoside analogues. Reports of cases of renal impairment w/ tenofovir alafenamide-containing products. Assess serum creatinine, estimated CrCl, urine glucose & urine protein in all patients prior to or when initiating therapy, & during treatment; in patients w/ CKD, assess also serum P. Cobicistat decreases estimated CrCl due to inhibition of tubular secretion of creatinine. Reports of increased bleeding, including spontaneous skin haematomas & haemarthrosis in patients w/ haemophilia type A & B treated w/ HIV PIs. Darunavir contains a sulphonamide moiety; caution in patients w/ known sulphonamide allergy. Increases in wt & blood lipid & glucose levels may occur during antiretroviral therapy. Reports of osteonecrosis particularly in patients w/ advanced HIV disease &/or long-term exposure to combination antiretroviral therapy. Reports of immune reactivation syndrome. Opportunistic infections & other HIV infection complications may continue to develop. Do not co-administer w/ other antiretroviral agents; medicinal products requiring pharmacokinetic enhancement w/ ritonavir or cobicistat; medicinal products containing tenofovir disoproxil (eg, fumarate, phosphate, or succinate), lamivudine, or adefovir dipivoxil used for HBV infection treatment. Caution in patients w/ mild or moderate hepatic impairment. Should not be initiated in patients w/ eGFR <30 mL/min. Dizziness may occur & may affect ability to drive & use machines. Women who become pregnant during therapy should be switched to an alternative regimen. Should not be initiated during pregnancy. Do not breastfeed while on treatment. Should not be used in childn <3 yr. Safety & efficacy in childn 3-11 yr, or weighing <40 kg, have not yet been established. Caution in elderly ≥65 yr.

Headache; diarrhoea; rash. Anaemia; hypersensitivity; DM, anorexia, hypercholesterolaemia, increased LDL, hypertriglyceridaemia, hyperlipidaemia, dyslipidaemia; abnormal dreams; dizziness; vomiting, nausea, abdominal pain & distension, dyspepsia, flatulence; increased hepatic enzyme; pruritus, urticaria; arthralgia, myalgia; asthenia, fatigue; increased blood creatinine.

Darunavir & cobicistat: Increased plasma conc of drugs that are primarily metabolised by CYP3A &/or CYP2D6 or are substrates of P-gp, BCRP, MATE1, OATP1B1 or OATP1B3. Co-administration w/ medicinal products that have active metabolite(s) formed by CYP3A may result in reduced plasma conc of these active metabolite(s). Lowered plasma conc w/ CYP3A inducers eg, efavirenz, carbamazepine, phenytoin, phenobarb, rifampicin, rifapentine, rifabutin, St. John's wort. Increased plasma conc w/ CYP3A inhibitors eg, azole antifungals. Emtricitabine: Co-administration w/ medicinal products that are eliminated by active tubular secretion may increase conc of emtricitabine, &/or the co-administered medicinal product. Increased conc w/ drugs that decrease renal function. Tenofovir alafenamide: Decreased absorption leading to loss of effect & development of resistance w/ P-gp inducers eg, rifampicin, rifabutin, carbamazepine, phenobarb. Increased absorption & plasma conc w/ P-gp inhibitors eg, cobicistat, ritonavir, ciclosporin. Distribution may be affected by OATP1B1 & OATP1B3 inducers/inhibitors.

Antivirals

J05AR22 - emtricitabine, tenofovir alafenamide, darunavir and cobicistat ; Belongs to the class of antivirals for treatment of HIV infections, combinations.

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