Darunavir oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing darunavir (as ethanolate)
Drugs List
Therapeutic Indications
Uses
HIV infection-combined with other antiretrovirals
Darunavir co-administered with ritonavir or cobicistat, and in combination with other antiretrovirals is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
Dosage
Darunavir is administered with ritonavir or cobicistat, and in combination with other antiretrovirals. Consult product information of co-administered drugs. Cobicistat is only indicated for once daily regimens.
Adults
Treatment experienced patients (With no darunavir resistance associated mutations (DRV-RAMs) and who have plasma HIV-1 RNA less than 100,000 copies/ml and CD4 cell count equal to or greater than 100 cells times 10 to the power of 6/litre)
800mg darunavir once daily with 100mg ritonavir once daily or 150mg cobicistat once daily.
Treatment experienced patients (All other patients)
600mg darunavir twice daily with 100mg ritonavir twice daily.
Treatment naive patients
800mg darunavir once daily with 100mg ritonavir once daily or 150mg cobicistat once daily.
Elderly
(See Dosage; Adult).
There is limited information available in the treatment of elderly patients with darunavir. Patients aged 65 and over should therefore be treated with caution due to an increased frequency of hepatic impairment and increased risk of lipodystrophy in this patient population.
Children
Treatment experienced children 3 to 17 years and weighing equal to or greater than 15kg (with no darunavir resistance mutations (DRV-RAMs) and who have plasma HIV-1 RNA less than 100,000 copies/ml and CD4 cell count equal to or greater than 100 cells times 10 to the power of 6/litre)
Equal to or greater than 15kg but less than 30kg: 600mg darunavir and 100mg ritonavir once daily.
Equal to or greater than 30kg but less than 40kg: 675mg darunavir and 100mg ritonavir once daily.
Equal to or greater than 40kg: 800 mg darunavir and 100mg ritonavir once daily OR 800mg darunavir and 150mg cobicistat (children 12 years or older) once daily.
The recommended dose of darunavir with low dose ritonavir should not exceed the recommended adult dose (800mg darunavir with 100mg ritonavir once daily).
Treatment experienced children 3 to 17 years and weighing equal to or greater than 15kg (All other patients)
Equal to or greater than 15kg but less than 30kg: 600mg darunavir and 100mg ritonavir once daily OR 380mg darunavir and 50mg ritonavir twice daily.
Equal to or greater than 30kg but less than 40kg: 675mg darunavir and 100mg ritonavir once daily OR 460mg darunavir and 60mg ritonavir twice daily.
Equal to or greater than 40kg: 800mg darunavir and 100mg ritonavir once daily OR 600mg darunavir and 100mg ritonavir twice daily.
The recommended dose of darunavir with low dose ritonavir should not exceed the recommended adult dose (800mg darunavir with 100mg ritonavir once daily OR 600mg darunavir with 100mg ritonavir twice daily).
Treatment naive children 3 to 17 years and weighing equal to or greater than 15kg
Equal to or greater than 15kg but less than 30kg: 600mg darunavir and 100mg ritonavir once daily.
Equal to or greater than 30kg but less than 40kg: 675mg darunavir and 100mg ritonavir once daily.
Equal to or greater than 40kg: 800mg darunavir and 100mg ritonavir once daily OR 800mg darunavir and 150mg cobicistat (children 12 years or older) once daily.
Patients with Hepatic Impairment
Darunavir is metabolised by the liver.
Severe hepatic impairment (Child-Pugh Class C)
Severe hepatic impairment may result in an increase in darunavir exposure and a worsening of its safety profile.
Additional Dosage Information
If a patient vomits within 4 hours of taking the medicine, another dose should be taken, with ritonavir, 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.
Administration
Must be administered in combination with ritonavir or cobicistat, and other antiretrovirals.
Patients taking darunavir should be instructed to take darunavir within 30 minutes after completion of a meal. The type of food does not affect the exposure to darunavir.
The use of only 75 mg and 150 mg tablets or the 100mg/ml oral suspension to achieve the recommended dose of darunavir is appropriate when there is a possibility of hypersensitivity to sunset yellow (E110). Sunset yellow is an excipient in the 400 mg or 600 mg tablets. The use of only 75 mg and 150 mg tablets or the 100 mg/ml oral suspension may also be used if there is difficulty in swallowing the 400 mg, 600 mg or 800 mg tablets.
Oral suspension
Shake bottle vigorously before each dose. The oral dosing pipette should not be used for any other medicinal products.
Contraindications
Children under 3 years
Children weighing less than 15kg
Breastfeeding
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Precautions and Warnings
Patients over 65 years
Acute porphyria
Diabetes mellitus
Haemophilia
Hepatitis
Hepatitis B
Hepatitis C
Mild hepatic impairment
Pregnancy
Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Some formulations contain sunset yellow (E110); may cause allergic reaction
Advise patient to take with or after food
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Evaluate for physical signs of fat redistribution
Monitor hepatic function
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 exacerbate diabetes mellitus
May precipitate diabetes mellitus
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Female: Oral contraception may not be adequate during treatment
Advise haemophiliac patients of possibility of increased bleeding
Take another dose if vomiting occurs within 4 hours
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.
Pregnancy and Lactation
Pregnancy
Use darunavir with caution in pregnancy.
The manufacturer suggests darunavir should only be used during pregnancy if the potential benefit justifies the risk, and that no dose adjustment is required when used in combination with ritonavir.
Briggs (2011) suggests that, if indicated the drug should not be withheld because of pregnancy.
Darunavir crosses the human placenta. At the time of writing, there is limited published experience concerning the use of darunavir during human pregnancy. Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. However, the absence of data regarding the use of darunavir during human pregnancy prevents a reliable risk assessment.
No association between protease inhibitors and an increased risk of gestational diabetes has been discovered. However, pregnant women being treated with protease inhibitors such as darunavir should be monitored for hyperglycaemia as this may lead to severe complications.
Briggs (2011) suggests administering zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Darunavir is contraindicated in breastfeeding.
HIV is known to be transmitted in milk therefore HIV-infected mothers should not breastfeed their infants in order to avoid transmission of HIV.
At the time of writing, there is limited published information concerning the use of darunavir during breastfeeding.
Studies in rats have demonstrated that darunavir is excreted in milk and at high levels (1,000 mg/kg/day) resulting 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.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Counselling
Advise patients to take with or just after food.
Advise patients that treatment with darunavir does not prevent the risk of transmission of HIV.
Missed dose
Advise patients taking the twice daily regimen:
If a dose is missed within 6 hours of the time it is usually taken, patients should be advised to take the dose with food as soon as possible.
If the missed dose is not remembered until more than 6 hours after the time it is usually taken, the missed dose should not be taken and the usual dosing schedule should be resumed.
Advise patients taking the once daily regimen:
If a dose is missed within 12 hours of the time it is usually taken, patients should be advised to take the dose as soon as possible.
If the missed dose is not remembered until more than 12 hours after the time it is usually taken, the missed dose should not be taken and the usual dosing schedule should be resumed.
Advise patient not to take St John's wort concurrently.
Advise patients to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Advise patient ability to drive and/or operate machinery may be affected by side effects.
Side Effects
Abdominal distension
Alopecia
Anaemia
Angina pectoris
Angioedema
Anorexia
Aphthous stomatitis
Asthenia
Attention disturbances
Autoimmune hepatitis
Blood disorders
Chest pain
Confusion
Conjunctival hyperaemia
Convulsions
Decrease in high density lipoprotein (HDL)
Depression
Diabetes mellitus
Disorientation
Disturbances of appetite
Dizziness
Dry eyes
Dry mouth
Dyspepsia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Eosinophilia
Epistaxis
Erectile dysfunction
Eructation
Fatigue
Flatulence
Flushing
Gamma glutamyl transferase (GGT) increased
Gastritis
Gastro-intestinal disturbances
Gastroesophageal reflux
Gout
Graves' disease
Gynaecomastia
Haematemesis
Headache
Hepatitis
Hepatomegaly
Herpes simplex
Hypercholesterolaemia
Hyperglycaemia
Hyperlipidaemia
Hypertension
Hypertriglyceridaemia
Hypoaesthesia
Immune Reactivation/Reconstitution Syndrome
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Insulin resistance
Lethargy
Leukopenia
Lipodystrophy
Memory disturbances
Metabolic disorders
Mood changes
Musculoskeletal disturbances
Myocardial infarction
Neutropenia
Osteonecrosis
Palpitations
Pancreatitis
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Polydipsia
Prolongation of QT interval
Pruritus
Pyrexia
Rash
Reduced libido
Renal disorders
Renal failure
Restlessness
Serum bilirubin increased
Sinus bradycardia
Skin disorder
Sleep disturbances
Stevens-Johnson syndrome
Stomatitis
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Thyroid abnormalities
Toxic epidermal necrolysis
Upper respiratory symptoms
Urinary abnormalities
Vertigo
Visual disturbances
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: January 2013
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Prezista 100 mg/ml oral suspension. Janssen-Cilag Ltd. Revised September 2020.
Summary of Product Characteristics: Prezista 75 mg, 150 mg, and 600 mg film-coated tablets. Janssen-Cilag Ltd. Revised September 2020.
Summary of Product Characteristics: Prezista 400 mg, and 800 mg film-coated tablets. Janssen-Cilag Ltd. Revised September 2020.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 September 2017
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Darunavir. Last revised: August 2, 2011.
Last accessed: January 28, 2013.
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.