Prezista

Therapy should be initiated by a healthcare provider experienced in the management of HIV infection. After therapy with PREZISTA has been initiated, patients should be advised not to alter the dosage, dose form or discontinue therapy without discussing with their healthcare provider.

The interaction profile of darunavir depends on whether ritonavir or cobicistat is used as pharmacokinetic enhancer. 5). Posology PREZISTA must always be given orally with cobicistat or low dose ritonavir as a pharmacokinetic enhancer and in combination with other antiretroviral medicinal products.

The Summary of Product Characteristics of cobicistat or ritonavir as appropriate, must therefore be consulted prior to initiation of therapy with PREZISTA. Cobicistat is not indicated for use in twice daily regimens or for use in the paediatric population less than 12 years of age and weighing less than 40 kg.

3 ART-naïve adult patients The recommended dose regimen is 800 mg once daily with cobicistat 150 mg once daily or ritonavir 100 mg once daily taken with food. ART-experienced adult patients The recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food.

A dose regimen of 800 mg once daily with cobicistat 150 mg once daily or ritonavir 100 mg once daily taken with food may be used in patients with prior exposure to antiretroviral medicinal products but without darunavir resistance associated mutations (DRV-RAMs)* and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/L.

* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V If HIV-1 genotype testing is not available, the recommended dose regimen is PREZISTA 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food.

ART-naïve paediatric patients (3 to 17 years of age and weighing at least 15 kg) The weight-based dose of PREZISTA taken with ritonavir or cobicistat taken with food in paediatric patients is provided in the table below. The dose of cobicistat to be used with PREZISTA in children less than 12 years of age has not been established.

2 ml) ritonavir once daily or 800 mg (8 ml) PREZISTA/150 mg (tablet) cobicistatb once daily a ritonavir oral solution: 80 mg/ml b adolescents 12 years and older c rounded up for suspension dosing convenience ART-experienced paediatric patients (3 to 17 years of age and weighing at least 15 kg) PREZISTA twice daily taken with ritonavir taken with food is usually recommended.

3% of subjects experienced at least one adverse reaction. 3 weeks. The most frequent adverse reactions reported in clinical trials and as spontaneous reports are diarrhoea, nausea, rash, headache and vomiting. The most frequent serious reactions are acute renal failure, myocardial infarction, immune reconstitution inflammatory syndrome, thrombocytopenia, osteonecrosis, diarrhoea, hepatitis and pyrexia.

26 In the 96 week analysis, the safety profile of PREZISTA/ritonavir 800/100 mg once daily in treatment-naïve subjects was similar to that seen with PREZISTA/ritonavir 600/100 mg twice daily in treatment-experienced subjects except for nausea which was observed more frequently in treatment-naïve subjects.

This was driven by mild intensity nausea. 5 weeks. 5% of subjects experienced at least one adverse reaction. 4 weeks. The most frequent adverse reactions reported were diarrhoea (28%), nausea (23%), and rash (16%). Serious adverse reactions are diabetes mellitus, (drug) hypersensitivity, immune reconstitution inflammatory syndrome, rash and vomiting.

For information on cobicistat, consult the cobicistat Summary of Product Characteristics. Tabulated list of adverse reactions Adverse reactions are listed by system organ class (SOC) and frequency category. Within each frequency category, adverse reactions are presented in order of decreasing seriousness.

Frequency categories are defined as follows: 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) and not known (frequency cannot be estimated from the available data). Adverse reactions observed with darunavir/ritonavir in clinical trials and post-marketing MedDRA system organ class Frequency category Adverse reaction Infections and infestations uncommon herpes simplex Blood and lymphatic system disorders uncommon thrombocytopenia, neutropenia, anaemia, leukopenia rare increased eosinophil count Immune system disorders uncommon immune reconstitution inflammatory syndrome, (drug) hypersensitivity Endocrine disorders uncommon hypothyroidism, increased blood thyroid stimulating hormone Metabolism and nutrition disorders common diabetes mellitus, hypertriglyceridaemia, hypercholesterolaemia, hyperlipidaemia uncommon gout, anorexia, decreased appetite, decreased weight, increased weight, hyperglycaemia, insulin resistance, decreased high density lipoprotein, increased appetite, polydipsia, increased blood lactate dehydrogenase Psychiatric disorders common insomnia uncommon depression, disorientation, anxiety, sleep disorder, abnormal dreams, nightmare, decreased libido rare confusional state, altered mood, restlessness 27 Nervous system disorders common headache, peripheral neuropathy, dizziness uncommon lethargy, paraesthesia, hypoaesthesia, dysgeusia, disturbance in attention, memory impairment, somnolence rare syncope, convulsion, ageusia, sleep phase rhythm disturbance Eye disorders uncommon conjunctival hyperaemia, dry eye rare visual disturbance Ear and labyrinth disorders uncommon vertigo Cardiac disorders uncommon myocardial infarction, angina pectoris, prolonged electrocardiogram QT, tachycardia rare acute myocardial infarction, sinus bradycardia, palpitations Vascular disorders uncommon hypertension, flushing Respiratory, thoracic and mediastinal disorders uncommon dyspnoea, cough, epistaxis, throat irritation rare rhinorrhoea Gastrointestinal disorders very common diarrhoea common vomiting, nausea, abdominal pain, increased blood amylase, dyspepsia, abdominal distension, flatulence uncommon pancreatitis, gastritis, gastrooesophageal reflux disease, aphthous stomatitis, retching, dry mouth, abdominal discomfort, constipation, increased lipase, eructation, oral dysaesthesia rare stomatitis, haematemesis, cheilitis, dry lip, coated tongue Hepatobiliary disorders common increased alanine aminotransferase uncommon hepatitis, cytolytic hepatitis, hepatic steatosis, hepatomegaly, increased transaminase, increased aspartate aminotransferase, increased blood bilirubin, increased blood alkaline phosphatase, increased gamma-glutamyltransferase Skin and subcutaneous tissue disorders common rash (including macular, maculopapular, papular, erythematous and pruritic rash), pruritus 28 uncommon angioedema, generalised rash, allergic dermatitis, urticaria, eczema, erythema, hyperhidrosis, night sweats, alopecia, acne, dry skin, nail pigmentation rare DRESS, Stevens-Johnson syndrome, erythema multiforme, dermatitis, seborrhoeic dermatitis, skin lesion, xeroderma not known toxic epidermal necrolysis, acute generalised exanthematous pustulosis Musculoskeletal and connective tissue disorders uncommon myalgia, osteonecrosis, muscle spasms, muscular weakness, arthralgia, pain in extremity, osteoporosis, increased blood creatine phosphokinase rare musculoskeletal stiffness, arthritis, joint stiffness Renal and urinary disorders uncommon acute renal failure, renal failure, nephrolithiasis, increased blood creatinine, proteinuria, bilirubinuria, dysuria, nocturia, pollakiuria rare decreased creatinine renal clearance rare crystal nephropathy§ Reproductive system and breast disorders uncommon erectile dysfunction, gynaecomastia General disorders and administration site conditions common asthenia, fatigue uncommon pyrexia, chest pain, peripheral oedema, malaise, feeling hot, irritability, pain rare chills, abnormal […]

Regular assessment of virological response is advised. In the setting of lack or loss of virological response, resistance testing should be performed. 2). The Summary of Product Characteristics of cobicistat or ritonavir as appropriate, must therefore be consulted prior to initiation of therapy with PREZISTA.

2 did not significantly affect darunavir concentrations. It is not recommended to alter the dose of cobicistat or ritonavir. Darunavir binds predominantly to 1-acid glycoprotein. This protein binding is concentration-dependent indicative for saturation of binding.

5). 2). Combinations with optimised background regimen (OBRs) other than ≥ 2 NRTIs have not been studied in this population. 1). 3). Pregnancy PREZISTA/ritonavir should be used during pregnancy only if the potential benefit justifies the potential risk.

2). 2). Cobicistat levels decrease and may not provide sufficient boosting. The substantial reduction in darunavir exposure may result in virological failure and an increased risk of mother to child transmission of HIV infection. 6). PREZISTA given with low dose ritonavir may be considered as an alternative.

2). 4% of patients. 1%) reported, and during post-marketing experience toxic epidermal necrolysis and acute generalised exanthematous pustulosis have been reported. PREZISTA should be discontinued immediately if signs or symptoms of severe skin reactions develop.

These can include, but are not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia. 8). Darunavir contains a sulphonamide moiety.

PREZISTA should be used with caution in patients with a known sulphonamide allergy. g. acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA. 5% of patients receiving combination antiretroviral therapy with PREZISTA/ritonavir.

1. Patients with severe (Child-Pugh Class C) hepatic impairment. 5). 5). - Strong CYP3A inducers such as rifampicin and herbal preparations containing St John’s Wort (Hypericum perforatum). 5). 6 Applicable to darunavir boosted with cobicistat, not when boosted with ritonavir: - Darunavir boosted with cobicistat is more sensitive for CYP3A induction than darunavir boosted with ritonavir.

Concomitant use with strong CYP3A inducers is contraindicated, since these may reduce the exposure to cobicistat and darunavir leading to loss of therapeutic effect. g. 5). Darunavir boosted with either ritonavir or cobicistat inhibits the elimination of active substances that are highly dependent on CYP3A for clearance, which results in increased exposure to the co-administered medicinal product.

Therefore, concomitant treatment with such medicinal products for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated (applies to darunavir boosted with either ritonavir or cobicistat).

g. 5).