x
For Healthcare Professionals Only

SYMTUZA®800 mg/150 mg/200 mg/10 mg film coated tablets PRESCRIBING INFORMATION

ACTIVE INGREDIENT(S):

darunavir, cobicistat, emtricitabine, tenofovir alafenamide

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

INDICATION(S):

Treatment of human immunodeficiency virus type 1 (HIV 1) infection in adults and adolescents (aged 12 years and older with body weight at least 40 kg). Genotypic testing should guide use.

DOSAGE & ADMINISTRATION:

Initiate by physician experienced in management of HIV 1 infection.

Adults and adolescents aged ≥ 12 years weighing ≥ 40 kg: one tablet daily with food in ART-naïve patients. ART-experienced patients: one tablet daily with food if no darunavir resistance associated mutations (DRV-RAMs) and plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l. If dose > 12 hours late, do not take missed dose and resume usual dosing schedule.

Children: Not established in children aged 3-11 years, or weighing < 40 kg. No data available. Should not be used below 3 years of age.
Elderly: Limited information; use with caution in patients > 65 years of age.
Renal impairment: eGFRCG ≥ 30 mL/min: no dose adjustment. eGFRCG < 30 mL/min: do not start/discontinue treatment as no data.
Hepatic impairment: mild (Child Pugh Class A)/moderate (Child Pugh Class B) hepatic impairment: no dose adjustment; use with caution. Severe hepatic impairment (Child Pugh Class C): not studied; do not use.

CONTRAINDICATIONS:

Hypersensitivity to active substances/excipients.
Severe (Child Pugh Class C) hepatic impairment.
Co-administration with carbamazepine, phenobarbital, phenytoin, rifampicin, lopinavir/ritonavir, St. John’s wort (Hypericum perforatum), alfuzosin, amiodarone, dronedarone, quinidine, ranolazine, colchicine (with renal and/or hepatic impairment), ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine), pimozide, quetiapine, sertindole, lurasidone, triazolam, midazolam administered orally, sildenafil (for treatment of pulmonary arterial hypertension), avanafil, simvastatin, lovastatin, lomitapide, ticagrelor.

SPECIAL WARNINGS & PRECAUTIONS:

Take precautions to prevent viral transmission.

ART-experienced patients: not for treatment-experienced patients with one or more DRV-RAMs or with HIV-1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 106/1.

Co-infection with hepatitis B/C virus: increased risk for severe, potentially fatal hepatic adverse reactions. Safety/efficacy not established when co infection with HIV 1 and hepatitis C virus (HCV). Tenofovir alafenamide active against HBV. Discontinuation of Symtuza may result in severe acute exacerbations of hepatitis if co-infection with HBV; monitor closely (clinical/laboratory follow up for at least several months after stopping Symtuza). With advanced liver disease or cirrhosis, discontinuation not recommended; post-treatment exacerbation of hepatitis may lead to hepatic decompensation. Do not use concomitantly with medicinal products containing tenofovir disoproxil (e.g. fumarate, phosphate, succinate), lamivudine, or adefovir dipivoxil (for HBV).

Mitochondrial dysfunction: mitochondrial dysfunction reported in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues. Main adverse reactions (often transitory) are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactataemia, hyperlipasaemia). Late onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour); not known if transient or permanent. Follow up/investigate any child exposed in utero. Follow current national recommendations for pregnant women.

Hepatotoxicity: Drug induced hepatitis reported with darunavir/ritonavir. Increased if pre existing liver dysfunction, including severe/potentially fatal hepatic adverse reactions. If concomitant antiviral therapy for hepatitis B or C, refer to relevant SmPCs. Conduct laboratory tests prior to initiating therapy; monitor during treatment. Consider increased AST/ALT monitoring with underlying chronic hepatitis, cirrhosis, pre treatment transaminase elevations, especially during first months. Consider prompt interruption/discontinuation of Symtuza if evidence of new/worsening liver dysfunction.

Nephrotoxicity: potential risk from chronic exposure to low levels of tenofovir alafenamide.

Renal impairment: Cobicistat decreases estimated creatinine clearance.

Haemophilia: reports of increased bleeding.

Severe skin reactions: Discontinue Symtuza immediately if signs/symptoms of severe skin reactions. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis reported with darunavir/ritonavir.

Sulphonamide allergy: caution; contains sulphonamide moiety.

Immune Reactivation Syndrome (IRIS):Inflammatory response to asymptomatic or residual opportunistic pathogens may arise in patients with severe immune deficiency at start of combination antiretroviral therapy (CART); evaluate symptoms when necessary. Herpes simplex/zoster reactivation observed with darunavir/ritonavir. Autoimmune disorders reported.

Opportunistic infections: can develop; close clinical observation required.

Other: Increase in weight, levels of blood lipids and glucose may occur, monitor blood lipids and glucose; refer to HIV treatment guidelines. Do not use Symtuza in combination with another antiretroviral requiring pharmaco-enhancement, with ritonavir, cobicistat, tenofovir disoproxil (as fumarate, phosphate or succinate), lamivudine or adefovir dipivoxil.

SIDE EFFECTS:

Very common: headache, diarrhoea, nausea, rash (including macular, maculopapular, papular, erythematous, pruritic rash, generalised rash, and allergic dermatitis), fatigue.
Common: hypersensitivity, anorexia, diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia, hyperlipidaemia, abnormal dreams, dizziness, vomiting, abdominal pain, abdominal distension, dyspepsia, flatulence, pancreatic enzymes increased, hepatic enzyme increased, angioedema, pruritus, urticaria, arthralgia, myalgia, asthenia, increased blood creatinine.
Other side effects: IRIS, pancreatitis acute, acute hepatitis, cytolytic hepatitis, DRESS, SJS, TEN, acute generalised exanthematous pustulosis, osteonecrosis.

Refer to SmPC for other side effects.

PREGNANCY:

Use only if potential benefit justifies potential risk.

LACTATION:

HIV infected women must not breast-feed under any circumstances.

INTERACTIONS:

Symtuza not studied; interactions identified in studies with individual components. Refer to the SmPC for full details before initiating therapy. See contraindications above.
Do not use: voriconazole (unless positive benefit risk ratio).
Not recommended: rifabutin, rifapentine, oxcarbazepine, efavirenz, bosentan, boceprevir, apixaban, dabigatran etexilate, rivaroxaban, everolimus, budesonide, fluticasone, simeprevir, salmeterol, tadalafil (for pulmonary arterial hypertension).
Use with caution: systemic dexamethasone, clarithromycin, artemether/lumefantrine, dasatinib, nilotinib, vinblastine, vincristine, sildenafil, vardenafil, tadalafil (erectile dysfunction).
Therapeutic drug monitoring advised: disopyramide, flecainide, mexiletine, propafenone, systemic lidocaine, ciclosporin, sirolimus, tacrolimus.
Clinical monitoring recommended &/or dose adjustment:alfentanil, digoxin, warfarin (monitor INR), clonazepam, paroxetine, sertraline, amitriptyline, desipramine, imipramine, nortriptyline, trazodone, metformin, clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole, colchicine (patients with normal renal/hepatic function), perphenazine, risperidone, thioridazine, carvedilol, metoprolol, timolol, amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil, prednisone, atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, methadone, buprenorphine/naloxone, fentanyl, oxycodone, tramadol, buspirone, clorazepate, diazepam, estazolam, flurazepam, parenteral midazolam, zolpidem, hormone replacement therapy (with oestrogen), drospirenone-containing product.
No dosing recommendations: oral contraceptives - alternative or additional contraceptive measures required.

Refer to SmPC for full details of interactions.

LEGAL CATEGORY: POM

PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS

PRESENTATIONS PACK SIZES MARKETING AUTHORISATION NUMBER(S) BASIC NHS COSTS
Bottle 30 tablets EU/1/17/1225/001 £672.97

MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.

FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.

Prescribing information last revised: February 2018

Adverse events should be reported. This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Janssen-Cilag Limited on 01494 567447 or at dsafety@its.jnj.com