Symtuza

HIV-1 infection in adults & adolescents (≥12 yr weighing at least 40 kg).

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

Should be taken with food: Do not crush.

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

Do not use in treatment-experienced patients w/ ≥1 darunavir resistance associated mutations (DRV-RAMs) or w/ HIV-1 RNA ≥100,000 copies/mL or CD4+ cell count <100 cells x 10⁶/L. Increased risk for severe & potentially fatal hepatic adverse reactions in patients w/ chronic hepatitis B or C treated w/ antiretroviral therapy. Safety & efficacy have not been established in patients co-infected w/ HIV-1 & HCV. Risk for severe acute exacerbations of hepatitis in patients co-infected w/ HIV & HBV who discontinue Symtuza, therefore closely monitor w/ both clinical & lab follow-up for at least several mth after stopping treatment. Treatment discontinuation is not recommended in patients w/ advanced liver disease or cirrhosis. Reports of mitochondrial dysfunction in HIV -ve infants exposed in utero &/or postnatally to nucleoside analogues. Increased risk for liver function abnormalities in patients w/ pre-existing liver dysfunction, including chronic hepatitis B or C. Interrupt or discontinue treatment if there is evidence of new or worsening liver dysfunction. Risk of renal impairment, including acute renal failure, proximal renal tubulopathy, & Fanconi syndrome. Increased risk of developing renal-related adverse reactions in patients taking tenofovir prodrugs who have impaired renal function & those taking nephrotoxic agents, including NSAIDs. Assess serum creatinine, estimated CrCl, urine glucose, & urine protein prior to or when initiating treatment & during treatment on a clinically appropriate schedule, & also assess serum P in patients w/ CKD. Discontinue treatment in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Cobicistat decreases estimated CrCl due to inhibition of tubular secretion of creatinine. Possibility of increased bleeding in haemophiliac patients. Reports of DRESS, SJS, TEN & acute generalised exanthematous pustulosis. Immediately discontinue treatment if signs or symptoms of severe skin reactions develop. Caution in patients w/ known sulphonamide allergy due to sulphonamide moiety in darunavir. Risk of increases in wt & in blood lipid & glucose levels. Reports of osteonecrosis, particularly in patients w/ advanced HIV disease &/or long-term exposure to combination antiretroviral therapy (CART). Reports of immune reconstitution inflammatory syndrome in HIV-infected patients treated w/ CART. Risk of opportunistic infections & other complications of HIV infection. Do not administer w/ other antiretroviral products. Do not concomitantly administer w/ medicinal products requiring pharmacokinetic enhancement w/ ritonavir or cobicistat. Do not concomitantly administer w/ medicinal products containing tenofovir disoproxil (as fumarate, phosphate or succinate), lamivudine, or adefovir dipivoxil used for HBV infection treatment. Minor influence on the ability to drive & use machines. Caution in patients w/ mild or moderate hepatic impairment. Do not initiate in patients w/ eGFR <30 mL/min. Discontinue in patients w/ eGFR that declines <30 mL/min during treatment. Do not initiate therapy during pregnancy. Women who become pregnant during therapy should be switched to an alternative regimen. Do not breastfeed while on treatment. Safety & efficacy have not yet been established in childn 3-11 yr or weighing <40 kg. Do not use in paed patients <3 yr. 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.

Increased plasma conc of apixaban, rivaroxaban; clonazepam; bosentan; elbasvir/grazoprevir; lomitapide. Decreased plasma conc of clopidogrel active metabolite. Darunavir & cobicistat: Increased systemic exposure of medicinal products primarily metabolised by CYP3A or transported by P-gp, BCRP, MATE1, OATP1B1 & 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). Decreased plasma conc w/ CYP3A inducers (eg, carbamazepine, phenobarb, phenytoin, oxcarbazepine, St. John's wort, rifampicin, rifabutin, rifapentine, systemic dexamethasone, bosentan, efavirenz). Increased plasma conc w/ CYP3A inhibitors (eg, clarithromycin, clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole). Increased plasma conc of alfuzosin; alfentanil; disopyramide, flecainide, mexiletine, propafenone, systemic lidocaine, amiodarone, dronedarone, ivabradine, quinidine, ranolazine, digoxin; clarithromycin; dabigatran etexilate, ticagrelor; paroxetine, sertraline, amitriptyline, desipramine, imipramine, nortriptyline, trazodone; metformin; clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole; colchicine; lumefantrine; dasatinib, nilotinib, vinblastine, vincristine, everolimus, irinotecan; perphenazine, risperidone, thioridazine, lurasidone, pimozide, quetiapine, sertindole; carvedilol, metoprolol, timolol; amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil; CYP3A-metabolised corticosteroids (including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone); ergot derivatives (eg, dihydroergotamine, ergometrine, ergotamine, methylergonovine); glecaprevir/pibrentasvir; atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, lovastatin, simvastatin; ciclosporin, sirolimus, tacrolimus, everolimus; salmeterol; buprenorphine &/or norbuprenorphine, methadone, fentanyl, oxycodone, tramadol; sildenafil, tadalafil, vardenafil, avanafil; buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam, zolpidem, triazolam. Altered plasma conc of warfarin; norethindrone. Increased or decreased plasma conc of voriconazole. 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/ medicinal products that decrease renal function. Tenofovir alafenamide: Decreased plasma conc w/ P-gp inducers (eg, carbamazepine, phenobarb, phenytoin, oxcarbazepine, St. John's wort, rifampicin, rifabutin, rifapentine). Increased plasma conc w/ P-gp inhibitors (eg, clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole, ciclosporin, cobicistat, ritonavir). Distribution may be affected by OATP1B1 & OATP1B3 activity.

Antivirals

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

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