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For Healthcare Professionals Only

PREZISTA® ORAL SUSPENSION and FILM-COATED TABLETS PRESCRIBING INFORMATION

ACTIVE INGREDIENT(S):

Darunavir (as ethanolate).

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

The PREZISTA SmPCs are available at:

Please click the following product name to access the full SmPC
PREZISTA 75 mg film-coated tablets
PREZISTA 100 mg/ml oral suspension
PREZISTA 150 mg film-coated tablets
PREZISTA 400 mg film-coated tablets
PREZISTA 600 mg film-coated tablets
PREZISTA 800 mg film coated tablets

INDICATION(S):

PREZISTA, co-administered with low dose ritonavir in combination with other antiretroviral medicinal products for treatment of patients with human immunodeficiency virus (HIV-1) infection.

PREZISTA Oral suspension, 400 mg and 800 mg tablets co-administered with cobicistat, in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in adults for once daily regimens. Cobicistat is not indicated in children.

PREZISTA Oral suspension, 75 mg, 150 mg and 600 mg tablets may be used to provide suitable dose regimens:

PREZISTA Oral suspension, 400 mg and 800 mg tablets may be used to provide suitable dose regimens in adult and paediatric patients from age 3 and at least 40kg body weight who are:

Genotypic or phenotypic testing (when available) and treatment history should guide use of PREZISTA.

DOSAGE & ADMINISTRATION:

Therapy should be initiated by health care provider experienced in management of HIV. Must be taken with food. PREZISTA oral suspension for patients unable to swallow tablets.

Adults:
ART-naïve adults: PREZISTA 800 mg once daily with cobicistat 150 mg or ritonavir 100 mg, once daily.
ART-experienced adults with no DRV-RAMs; PREZISTA 800 mg once daily with cobicistat 150 mg or ritonavir 100 mg, once daily.
All other ART-experienced adults: 600 mg PREZISTA with 100 mg ritonavir twice daily.

Children:
ART-naïve children (3-17 years of age):
Body weight ≥15kg to <30kg: 600 mg (6ml) PREZISTA/100 mg (1.2ml) ritonavir, once daily.
Body weight ≥30kg to <40kg: 675 mg (6.8ml) PREZISTA/100 mg (1.2ml) ritonavir, once daily.
Body weight ≥40kg: 800 mg (8ml) PREZISTA/100 mg (1.2ml) ritonavir, once daily.
ART-experienced children (3-17 years of age, weighing at least 15kg) with no DRV-RAMs: a regimen of PREZISTA, twice daily with ritonavir is usually recommended.
Please refer to SmPC for dosage regimens.

Children:
<3 years or <15 kg body weight: Not recommended.

Elderly: Caution; limited information.
Renal impairment: No dose adjustment required for PREZISTA/ritonavir patients. No experience with PREZISTA/cobicistat. Cobicistat should not be initiated in patients with creatinine clearance less than 70ml/min if any co-administered agent requires dose adjustment based on creatinine clearance. Refer to the cobicistat SmPC.
Hepatic impairment: Caution with mild/moderate hepatic impairment; contraindicated with severe hepatic impairment.
Pregnancy and postpartum: No dose adjustment required.

CONTRAINDICATIONS:

Hypersensitivity to active substance or any excipients. Severe hepatic impairment.

Applicable to PREZISTA/ritonavir or cobicistat: Co-administration with rifampicin or lopinavir/ritonavir combination product. Preparations containing St John's wort. Active substances highly dependent on CYP3A for clearance including alfuzosin, amiodarone, bepridil, dronedarone, quinidine, ranolazine, lidocaine (systemic), astemizole, terfenadine, colchicine (in patients with renal and/or hepatic impairment), dihydroergotamine, ergometrine, ergotamine, methylergonovine, elbasvir/grazoprevir, cisapride, lurasidone, pimozide, quetiapine, sertindole, triazolam, midazolam (oral), sildenafil (for pulmonary arterial hypertension), avanafil, simvastatin, lovastatin, ticagrelor.

Applicable to PREZISTA/cobicistat: Active substances highly dependent on CYP3A for clearance including carbamazepine, phenobarbital and phenytoin.

SPECIAL WARNINGS & PRECAUTIONS:

Regular assessment of virological response advised. Perform resistance testing if lack/loss of virological response. Do not use PREZISTA/ritonavir or cobicistat once daily dose regimen in ART-experienced patients with one or more DRV-RAMs. Advise patients to take precautions to avoid transmission. PREZISTA must always be given with cobicistat or ritonavir, consult the cobicistat or ritonavir SmPC prior to initiation.
Severe skin reactions: Discontinue PREZISTA/ritonavir or cobicistat immediately if signs or symptoms of severe skin reactions develop. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis reported.
Rash: In clinical studies rash occurred more commonly in treatment-experienced patients receiving both PREZISTA/ritonavir + raltegravir compared to patients on PREZISTA/ritonavir without raltegravir.
Patients with known sulphonamide allergy: Caution; contains sulphonamide moiety.
Hepatotoxicity: Appropriate laboratory testing prior to initiation, with continuous monitoring during treatment. Drug-induced hepatitis reported. Patients with pre-existing liver dysfunction including chronic active hepatitis B or C have increased risk of liver function abnormalities including severe/potentially fatal hepatic adverse events should be monitored. Prompt interruption/discontinuation of treatment if liver disease develops or worsens.
Haemophiliac patients: Possibility of increased bleeding.
Pregnancy: Caution in pregnant women with concomitant medications which may further decrease darunavir exposure.
Immune reconstitution inflammatory syndrome (IRIS): Inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise in immune reactive patients with severe immune deficiency at start of combination antiretroviral therapy (CART). Autoimmune disorders reported in IRIS.
Other: Increased weight, levels of blood lipids and glucose may occur, may partly be linked to disease control and life style. Monitor blood lipids and glucose; refer to HIV treatment guidelines; manage as appropriate. Patients with advanced HIV disease and/or long-term exposure to CART may develop osteonecrosis. Life-threatening/fatal drug interactions reported in patients treated with colchicine and powerful CYP3A and P-glycoprotein inhibitors. Patients with renal or hepatic impairment should not be given colchicine with PREZISTA/ritonavir or cobicistat. If switching from ritonavir to cobicistat, caution required during first two weeks of treatment, particularly if there was a dose titration/adjustment of concomitant medication.

SIDE EFFECTS:

Refer to SmPC for other side effects.
Safety profile in children/adolescents similar to adults.

Applicable to PREZISTA/ritonavir:
Very common: diarrhoea.
Common: hypertriglyceridaemia, diabetes mellitus, hypercholesterolaemia, hyperlipidaemia, insomnia, headache, peripheral neuropathy, dizziness, vomiting, nausea, abdominal pain, increased blood amylase, dyspepsia, abdominal distension, flatulence, increased alanine aminotransferase, rash, pruritus, asthenia, fatigue.
Other side effects: herpes simplex, thrombocytopenia, neutropenia, leukopenia, immune reconstitution inflammatory syndrome (IRIS), convulsion, (acute) myocardial infarction, angina pectoris, prolonged electrocardiogram QT, pancreatitis, haematemesis, hepatitis*, cytolytic hepatitis*, angioedema, osteonecrosis*, acute renal failure, nephrolithiasis, pyrexia, DRESS*, SJS*, erythema multiforme, TEN*, acute generalised exanthematous pustulosis*.

Applicable to PREZISTA/cobicistat:
Very common: headache, diarrhoea, nausea, rash.
Common: (drug) hypersensitivity, anorexia, diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia, hyperlipidaemia, abnormal dreams, vomiting, abdominal pain, abdominal distension, dyspepsia, flatulence, pancreatic enzymes increased, hepatic enzyme increased, angioedema, pruritus, urticaria, myalgia, fatigue, increased blood creatinine.
Other side effects: pancreatitis acute, IRIS.

* adverse drug reactions noted with PREZISTA/ritonavir treatment could be expected with PREZISTA/cobicistat.

Refer to SmPC for other side effects.

PREGNANCY:

Use during pregnancy only if potential benefit justifies potential risk.

LACTATION:

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

INTERACTIONS:

Refer to the SmPC for full details before initiating therapy.
Interaction studies in adults only.

Applicable to PREZISTA/ritonavir:
Do not use: phenobarbital, phenytoin.
Not recommended: saquinavir. Clinical monitoring recommended &/or dose adjustment: efavirenz, carbamazepine, rifabutin, bosentan, indinavir.
Recommended dose: elvitegravir 150 mg daily.

Applicable to PREZISTA/ritonavir or cobicistat:
Do not use: voriconazole (unless positive benefit risk ratio).
Not recommended: apixaban, dabigatran etexilate, rivaroxaban, rifapentine, everolimus, betamethasone, mometasone, prednisone, triamcinolone, fluticasone, budesonide, boceprevir, simeprevir, telaprevir, salmeterol, tadalafil (for pulmonary arterial hypertension).
Use with caution: clarithromycin, artemether/lumefantrine, dasatinib, nilotinib, vinblastine, vincristine, dexamethasone (systemic), sildenafil, tadalafil, vardenafil (erectile dysfunction).
Therapeutic drug monitoring advised: disopyramide, flecainide, mexiletine, propafenone, ciclosporin, sirolimus, tacrolimus.
Clinical monitoring recommended &/or dose adjustment: tenofovir disoproxil fumarate, alfentanil, digoxin, warfarin (INR), paroxetine, sertraline, amitriptyline, desipramine, imipramine, nortriptyline, trazodone, ketoconazole, itraconazole, fluconazole, posaconazole, clotrimazole, colchicine (normal renal / hepatic function), perphenazine, risperidone, thioridazine, carvedilol, metoprolol, timolol, amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil, predisone, atorvastatin, pravastatin, rosuvastatin,  methadone, buprenorphine/naloxone, buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam (parenteral), zoldipem.
Recommended dose: maraviroc (150 mg twice daily).
No dosing recommendations: oral contraceptives alternative or additional contraceptive measures required.

Applicable to PREZISTA/cobicistat:
Do not use: atazanavir, indinavir, saquinavir.
Not recommended: elvitegravir, efavirenz, etravirine, nevirapine, rifabutin, bosentan.
Clinical monitoring recommended &/or dose adjustment: metformin.
Refer to SmPC for full details of interactions.

LEGAL CATEGORY: POM.

PRESENTATION(S), PACK SIZE(S), MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COST(S)

PRESENTATION(S) PACK SIZE(S) MARKETING AUTHORISATION NUMBER(S) BASIC NHS COST(S)
100 mg/ml oral suspension 200ml EU/1/06/380/006 £248.17
75 mg tablets 480 tablets EU/1/06/380/005 £446.70
150 mg tablets 240 tablets EU/1/06/380/004 £446.70
400 mg tablets 60 tablets EU/1/06/380/003 £297.80
600 mg tablets 60 tablets EU/1/06/380/002 £446.70
800 mg tablets 30 tablets EU/1/06/380/007 £297.80

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 2017

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Janssen-Cilag Limited on 01494 567447 or at dsafety@its.jnj.com.