Darunavir Viatris (Previously Darunavir Mylan)

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

Posology Darunavir Viatris must always be given orally with low dose ritonavir as a pharmacokinetic enhancer and in combination with other antiretroviral medicinal products. The Summary of Product Characteristics of ritonavir must, therefore, be consulted prior to initiation of therapy with darunavir.

ART-experienced adult patients The recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food. Darunavir Viatris 75 mg, 150 mg, 300 mg and 600 mg tablets can be used to construct the twice daily 600 mg regimen.

The use of 75 mg and 150 mg tablets to achieve the recommended dose is appropriate when there is a difficulty in swallowing the 300 mg or 600 mg tablets. Before prescribing darunavir tablets, young children should be assessed for the ability to swallow intact tablets.

For young children unable to swallow tablets, more suitable formulations containing darunavir should be checked for their availability. ART-naïve adult patients For dosage recommendations in ART-naïve patients see the Summary of Product Characteristics for Darunavir Viatris 400 mg and 800 mg tablets.

ART-naïve paediatric patients (3 to 17 years of age and weighing at least 15 kg) The weight-based dose of darunavir and ritonavir in paediatric patients is provided in the table below. 4 Recommended dose for treatment-naïve paediatric patients (3 to 17 years) with darunavir tablets and ritonavira Body weight (kg) Dose (once daily with food) ≥ 15 kg to < 30 kg 600 mg darunavir/100 mg ritonavir once daily ≥ 30 kg to < 40 kg 675 mg darunavir/100 mg ritonavir once daily ≥ 40 kg 800 mg darunavir/100 mg ritonavir once daily a ritonavir oral solution: 80 mg/ml ART-experienced paediatric patients (3 to 17 years of age and weighing at least 15 kg) Darunavir twice daily taken with ritonavir taken with food is usually recommended.

A once daily dose regimen of darunavir taken with ritonavir 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.

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.

In the 96 week analysis, the safety profile of darunavir/ ritonavir 800/100 mg once daily in treatment- naïve subjects was similar to that seen with darunavir/ 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. 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, leucopenia 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 25 MedDRA system organ class Frequency category Adverse reaction Psychiatric disorders Common insomnia Uncommon depression, disorientation, anxiety, sleep disorder, abnormal dreams, nightmare, decreased libido Rare confusional state, altered mood, restlessness 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 26 MedDRA system organ class Frequency category Adverse reaction 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 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 feeling, xerosis § adverse reaction identified in the post-marketing setting.

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 ritonavir as appropriate, must therefore be consulted prior to initiation of therapy with darunavir.

2 did not significantly affect darunavir concentrations. It is not recommended to alter the dose of ritonavir. Darunavir binds predominantly to α1-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 Darunavir/ritonavir should be used during pregnancy only if the potential benefit justifies the potential risk.

2). 2). 4% of patients. 1%) reported, and during post-marketing experience toxic epidermal necrolysis and acute generalised exanthematous pustulosis have been reported. Darunavir should be 7 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.

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

Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe and potentially fatal hepatic adverse reactions. In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products.

1. Patients with severe (Child-Pugh Class C) hepatic impairment. 5). 5). 5). Co-administration of darunavir with low dose ritonavir, with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.

g. 5).