Darunavir with cobicstat, emtricitabine and tenofovir alafenamide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of darunavir with cobicistat, emtricitabine and tenofovir alafenamide.
Drugs List
Therapeutic Indications
Uses
HIV infection in adults and adolescents over 12 years: treatment
Treatment of adults and adolescents (aged 12 years or older, with a body weight of at least 40kg) infected with HIV-1.
Dosage
Adults
One tablet once daily, taken with food.
Additional Dosage Information
Missed doses
If a dose is missed, take the prescribed dose as soon as possible, but within 12 hours of the time it is usually taken. The dose should not be taken if a missed dose is noticed more than 12 hours after the time it is usually taken.
Contraindications
Children under 3 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Precautions and Warnings
Children aged 3 to 11 years
Children with body weight under 40kg
Patients over 65 years
Hepatic impairment - Child-Pugh score between 5 and 9
Hepatitis
Hepatitis B
Hepatitis C
Cirrhosis: Monitor for signs and symptoms of hepatic decompensation
Monitor HBV levels during and after treatment in patients with co-infection
Switch to more suitable alternative before planned pregnancy
Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
Herpes zoster reactivation possible - consider antiviral prophylaxis
Treatment should be initiated by doctor experienced in HIV management
Monitor blood lipids before and during treatment
Monitor hepatic function before treatment and regularly during treatment
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor children exposed in utero for mitochondrial impairment
Advise patient to seek medical advice if joint aches or pain occur
Risk of developing opportunistic infections
Advise patient to seek advice at first indications of pregnancy
Consider discontinuing treatment if severe hepatic changes occur
Discontinue if eGFR falls below 30ml/minute/1.73 m squared
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Advise haemophiliac patients of possibility of increased bleeding
Take another dose if vomiting occurs within one hour
Darunavir with cobicistat, emtricitabine and tenofovir alafenamide should not be used in treatment experienced patients in the following cases:
One or more DRV-RAMs,
HIV-1 RNA greater than or equal to 100,000 copies/ml,
CD4+ cell count less than 100 cells times 10 to the power 6/litre.
When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis jiroveci pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.
Patients co-infected with hepatitis B or C are at an increased risk of severe, potentially fatal hepatic adverse events. When discontinuing treatment with darunavir with cobicistat, emtricitabine and tenofovir alafenamide in these patients, monitor patients closely for several months after treatment. Hepatitis B treatment may be warranted.
Darunavir with cobicistat, emtricitabine and tenofovir alafenamide may decrease estimated creatinine clearance, due to inhibition of creatinine secretion from renal tubules. This effect on estimated creatinine clearance may impact the clinical management of aspects of the patient's treatment, including dose adjustment of co-administered medicinal products.
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 months of darunavir with cobicistat, emtricitabine and tenofovir alafenamide treatment.
Pregnancy and Lactation
Pregnancy
Darunavir with cobicistat, emtricitabine and tenofovir alafenamide is contraindicated during pregnancy.
The manufacturer does not recommend darunavir with cobicistat, emtricitabine and tenofovir alafenamide treatment to be initiated during pregnancy and women who become pregnant during therapy with this product should be switched to an alternative regimen. At the time of writing there is limited published information regarding the use of darunavir with cobicistat, emtricitabine and tenofovir alafenamide during pregnancy. Potential risks are unknown.
Lactation
Darunavir with cobicistat, emtricitabine and tenofovir alafenamide is contraindicated during breastfeeding.
Use of darunavir with cobicistat, emtricitabine and tenofovir alafenamide is contraindicated by the manufacturer. Animal data reports significant levels of darunavir with cobicistat, emtricitabine and tenofovir alafenamide in the breast milk, however presence in human breast milk and the effect on exposed infants are unknown.
Side Effects
Abdominal distension
Abdominal pain
Acute generalised exanthematous pustulosis
Acute pancreatitis
Allergic dermatitis
Alterations in pancreatic enzymes
Anaemia
Angioedema
Anorexia
Arthralgia
Asthenia
Autoimmune hepatitis
Cytolytic hepatitis
Diabetes mellitus
Diarrhoea
Dizziness
Dream abnormalities
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyspepsia
Erythematous rash
Fatigue
Flatulence
Graves' disease
Gynaecomastia
Headache
Hepatitis (transient)
Hypercholesterolaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Immune Reactivation/Reconstitution Syndrome
Increase in blood urea or creatinine
Increases in hepatic enzymes
Localised and generalised rash
Macular rash
Maculopapular rash
Myalgia
Nausea
Osteonecrosis
Pruritic rash
Pruritus
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: December 2019
Reference Sources
Summary of Product Characteristics: Symtuza 800mg/150mg/200mg/10mg film-coated tablets. Janssen-Cilag Ltd. Revised July 2019.
MHRA Drug Safety Update April 2019
Available at: https://www.mhra.gov.uk
Last accessed: 22 May 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.