Darunavir with cobicistat oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of darunavir (as ethanolate) with cobicistat.
Drugs List
Therapeutic Indications
Uses
HIV infection-combined with other antiretrovirals
Dosage
Adults
1 tablet once a day, taken with food.
Children
Children aged 12 to 18 years weighing at least 40kg
1 tablet once a day, taken with food.
Patients with Renal Impairment
Patients with creatinine clearance less than 70ml/minute that are being co-administered agents requiring dose adjustments based on creatinine clearance should not be treated with darunavir with cobicistat.
Additional Dosage Information
For patients unable to swallow the whole tablet, the tablet may be split into two pieces and should be consumed immediately after splitting.
If a patient vomits within 4 hours of taking the medicine, another dose should be taken 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 dose.
Missed dose
Advise patient if they miss a dose within 12 hours of the time it is usually taken, the patient should take the missed dose with food as soon as possible and resume normal dosing schedule. If a patient misses a dose by more than 12 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
Contraindications
Children under 3 years
Children with body weight under 40kg
Breastfeeding
Pregnancy
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Precautions and Warnings
Children aged 3 to 12 years
Patients over 65 years
Haemophilia
Hepatic impairment
Hepatitis
Hepatitis B
Hepatitis C
Renal impairment - creatinine clearance below 70ml/min
Switch to more suitable alternative before planned pregnancy
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Treatment should be initiated by doctor experienced in HIV management
Advise patient to take with or after food
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
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Inflammatory symptoms should be evaluated and treated appropriately
May cause weight gain
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 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 4 hours
Darunavir with cobicistat 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 per ml or CD4+ cell count less than 100 cells times 10 to the power 6 per 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.
Blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.
Pregnancy and Lactation
Pregnancy
Darunavir with cobicistat is contraindicated during pregnancy.
The manufacturer does not recommend darunavir with cobicistat treatment to be initiated during pregnancy and women who become pregnant during therapy with this product should be switched to an alternative regimen.
Treatment with cobicistat and darunavir during second and third trimester of pregnancy has shown to substantially lower darunavir exposure, which may result in virological failure and increase the risk of transmission of HIV from the mother to infant. Animal studies do not indicate harmful effects.
Lactation
Darunavir with cobicistat is contraindicated in breastfeeding.
It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant. Due to the potential for HIV transmission and potential for adverse effects breastfeeding should not take place.
At the time of writing, there is limited published information regarding the use of darunavir with cobicistat in breastfeeding. Animal studies have shown that darunavir is excreted in milk at high levels, which resulted in toxicity. It is not known whether darunavir is excreted in human milk. However, due to the low molecular weight and prolonged elimination half-life, it is considered likely that darunavir will be excreted in breast milk. Animal studies have shown cobicistat to be excreted in milk.
Side Effects
Abdominal distension
Abdominal pain
Acute generalised exanthematous pustulosis
Acute renal failure
Alterations in pancreatic enzymes
Angioedema
Anorexia
Asthenia
Autoimmune hepatitis
Creatine phosphokinase increased
Cytolytic hepatitis
Decrease in creatinine clearance
Diabetes mellitus
Diarrhoea
Dream abnormalities
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyspepsia
Fatigue
Flatulence
Graves' disease
Gynaecomastia
Headache
Hepatitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Immune Reactivation/Reconstitution Syndrome
Increased spontaneous bleeding (haemophiliacs)
Increases in hepatic enzymes
Inflammatory reactions
Myalgia
Myositis
Nausea
Osteonecrosis
Pancreatitis
Pruritus
Pyrexia
Rash
Rhabdomyolysis
Rise in blood lipids
Serum creatinine increased
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Vomiting
Weight changes
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: October 2019.
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Rezolsta 800 mg/15 mg tablets. Janssen-Cilag Ltd. Revised March 2020.
MHRA Drug Safety Update April 2019
Available at: https://www.mhra.gov.uk
Last accessed: 22 May 2019
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 October 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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