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Rezolsta is a brand name for Darunavir. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: REZOLSTA is indicated, in combination with other antiretroviral medicinal products, for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults and paediatric patients (aged 6 years and older, weighing at least 25 kg). Genotypic testing should guide the use of REZOLSTA (see sections 4.2, 4.4 and…
Verbatim from this product's EMA label. Tap a section to expand.
Therapy should be initiated by a healthcare provider experienced in the management of HIV infection. Posology Adults and paediatric patients weighing at least 40 kg ART-naïve patients The recommended dose regimen is one 800 mg darunavir/150 mg cobicistat tablet once daily taken with food.
1). * DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, L89V. Paediatric patients aged 6 years and older weighing at least 25 kg to less than 40 kg ART-naïve paediatric patients The recommended dose regimen is one 675 mg darunavir/150 mg cobicistat tablet once daily taken with food.
1). * DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, L89V. In all other ART-experienced patients or if HIV-1 genotype testing is not available, the use of REZOLSTA is not appropriate and another antiretroviral regimen should be used.
Refer to the Summary of Product Characteristics of other antiretroviral medicinal products for dosing information. Advice on missed doses If REZOLSTA is missed within 12 hours of the time it is usually taken, patients should be instructed to take the prescribed dose with food as soon as possible.
If this is noticed later than 12 hours of the time it is usually taken, the missed dose should not be taken and the patient should resume the usual dosing schedule. If a patient vomits within 4 hours of taking the medicine, another dose of REZOLSTA should be taken with food as soon as possible.
If a patient vomits more than 4 hours after taking the medicine, the patient does not need to take another dose until the next regularly scheduled time. 2). Hepatic impairment There are no pharmacokinetic data regarding the use of REZOLSTA in patients with hepatic impairment.
Darunavir and cobicistat are metabolised by the hepatic system. Separate trials of darunavir/ritonavir and cobicistat suggest no dose adjustment is recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, however, REZOLSTA should be used with caution in these patients.
There are no data regarding the use of darunavir or cobicistat in patients with severe hepatic impairment. Severe hepatic impairment could result in an increase of darunavir and/or cobicistat exposure and a worsening of its safety profile.
Summary of the safety profile The overall safety profile of REZOLSTA is based on available clinical trial data from darunavir boosted with either cobicistat or ritonavir, from cobicistat and from post-marketing data from darunavir/ritonavir.
As REZOLSTA contains darunavir and cobicistat, the adverse reactions associated with each of the individual compounds may be expected. The most frequent adverse reactions reported in the pooled data of the Phase III study GS-US-216-130 and the REZOLSTA arm of Phase III study TMC114FD2HTX3001 were diarrhoea (23%), nausea (17%), rash (13%), and headache (10%).
Serious adverse reactions were diabetes mellitus, (drug) hypersensitivity, immune reconstitution inflammatory syndrome, rash, Stevens-Johnson syndrome, and vomiting. 6%) subjects. The most frequent adverse reactions reported during the darunavir/ritonavir clinical development program 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. Tabulated list of adverse reactions Adverse reactions are listed by system organ class (SOC) and frequency category in Table 2. 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). 21 Table 2 Adverse reactions with darunavir/cobicistat in adult patients MedDRA system organ class Frequency category Adverse reaction Immune system disorders Common (drug) hypersensitivity Uncommon immune reconstitution inflammatory syndrome Metabolism and nutrition disorders Common anorexia, hypercholesterolaemia, hypertriglyceridaemia Uncommon diabetes mellitus, dyslipidaemia, hyperglycaemia, hyperlipidaemia Psychiatric disorders Common abnormal dreams Nervous system disorders Very common headache Gastrointestinal disorders Very common diarrhoea, nausea Common vomiting, abdominal pain, abdominal distension, dyspepsia, flatulence Uncommon pancreatitis acute, pancreatic enzymes increased Hepatobiliary disorders Common hepatic enzyme increased Uncommon hepatitis*, cytolytic hepatitis* Skin and subcutaneous tissue disorders Very common rash (including macular, maculopapular, papular, erythematous, pruritic rash, generalised rash, and allergic dermatitis) Common pruritus Uncommon Stevens-Johnson syndrome#, angioedema, urticaria Rare drug reaction with eosinophilia and systemic symptoms* Not known toxic epidermal necrolysis*, acute generalised exanthematous pustulosis* Musculoskeletal and connective tissue disorders Common myalgia Uncommon osteonecrosis* Renal and urinary disorders Rare crystal nephropathy*§ Reproductive system and breast disorders Uncommon gynaecomastia* General disorders and administration site conditions Common fatigue, asthenia 22 Investigations Common increased blood creatinine * These adverse drug reactions have not been reported in clinical trial experience with darunavir/cobicistat but have been noted with darunavir/ritonavir treatment and could be expected with darunavir/cobicistat too.
Regular assessment of virological response is advised. In the setting of lack or loss of virological response, resistance testing should be performed. Darunavir binds predominantly to α1-acid glycoprotein. This protein binding is concentration dependent indicative for saturation of binding.
5). 2). Combinations with optimised background regimens (OBRs) other than ≥ 2 NRTIs have not been studied in this population. 1). 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). Darunavir 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.
REZOLSTA 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 with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
8). Sulphonamide allergy Darunavir contains a sulphonamide moiety. REZOLSTA should be used with caution in patients with a known sulphonamide allergy. g. acute hepatitis, cytolytic hepatitis) has been reported with darunavir/ritonavir.
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. Appropriate laboratory testing should be conducted prior to initiating therapy with REZOLSTA and patients should be monitored during treatment.
1. Patients with severe (Child-Pugh Class C) hepatic impairment. 5): - carbamazepine, phenobarbital, phenytoin - rifampicin - lopinavir/ritonavir - St John’s Wort (Hypericum perforatum). g. 5) - ticagrelor.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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2). Renal impairment Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine. g. 2). Based on the very limited renal elimination of cobicistat and darunavir, no special precautions or dose adjustments of REZOLSTA are required for patients with renal impairment.
2). For more information consult the cobicistat Summary of Product Characteristics. Paediatric population The safety and efficacy of darunavir in combination with cobicistat in paediatric patients aged 3 to < 6 years, or weighing < 25 kg, have not been established.
No data are available yet. 3). 2). 6). Darunavir/ritonavir may be considered as an alternative. Method of administration Oral use To ensure administration of the entire dose of both darunavir and cobicistat, the tablet should be swallowed whole.
2). Adults and paediatric patients weighing at least 40 kg For patients unable to swallow the 800 mg/150 mg tablet whole, the tablet may be split into two pieces using a tablet-cutter. Each piece should be consumed immediately after splitting to ensure the entire dose is administered.
Paediatric patients aged 6 years and older weighing at least 25 kg to less than 40 kg For patients unable to swallow the 675 mg/150 mg tablet whole, the scored tablet may be split by hand into two pieces. Each piece should be consumed immediately after splitting to ensure the entire dose is administered.
4). § Adverse reaction identified in the post-marketing setting. Per the guideline on Summary of Product Characteristics (Revision 2, September 2009), the frequency of this adverse reaction in the post-marketing setting was determined using the "Rule of 3".
4). 9% of patients discontinued treatment due to rash. 4). Musculoskeletal abnormalities Increased CPK, myalgia, myositis and, rarely, rhabdomyolysis have been reported with the use of HIV protease inhibitors, particularly in combination with NRTIs.
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). 4). Immune reconstitution inflammatory syndrome In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.
4). Bleeding in […]
Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of treatment.
If there is evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) interruption or discontinuation of treatment should be considered promptly.
Patients with coexisting conditions Hepatic impairment The safety and efficacy of darunavir and/or cobicistat have not been established in patients with severe underlying liver disorders. REZOLSTA is, therefore, contraindicated in patients with severe hepatic impairment.
2). Renal impairment Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine. This effect on serum creatinine, leading to a decrease in the estimated creatinine clearance, should be taken into consideration when REZOLSTA is administered to patients, in whom the estimated creatinine clearance is used to guide aspects of their clinical management, including adjusting doses of co-administered medicinal products.
For more information consult the cobicistat Summary of Product Characteristics. g. 2). No special precautions or dose adjustments are required in patients with renal impairment. 2). There are currently inadequate data […]