ANTIVIRALS›HIV-INTEGRASE INHIBITORS
Dolutegravir 05-Jun-2018
lDRUG ACTIONDolutegravir is an inhibitor of HIV
integrase.
lINDICATIONS AND DOSE
HIV infection without resistance to other inhibitors of HIV
integrase, in combination with other antiretroviral drugs
▶BY MOUTH
▶Child 12–17 years (body-weight 40 kg and above): 50 mg
once daily
HIV infection in combination with other antiretroviral
drugs (with concomitant carbamazepine, efavirenz,
etravirine (without boosted protease inhibitors, but see
also Interactions), fosphenytoin, phenobarbital,
phenytoin, primidone, nevirapine, oxcarbazepine, St
John’s wort, rifampicin, or tipranavir)
▶BY MOUTH
▶Child 12–17 years (body-weight 40 kg and above): 50 mg
twice daily, avoid concomitant use with these drugs if
resistance to other inhibitors of HIV integrase
suspectedIMPORTANT SAFETY INFORMATION
MHRA/CHM ADVICE:TIVICAY®(DOLUTEGRAVIR),TRIUMEQ®
(DOLUTEGRAVIR, ABACAVIR, LAMIVUDINE),JULUCA®
(DOLUTEGRAVIR, RILPIVIRINE): NEURAL TUBE DEFECTS
REPORTED IN INFANTS BORN TO WOMEN EXPOSED TO
DOLUTEGRAVIR AT THE TIME OF CONCEPTION (MAY 2018)
In an ongoing birth outcome surveillance study
conducted in Botswana, 4 cases of neural tube defects
have been reported in 426 infants born to women who
took dolutegravir as part of combined antiretroviral
therapy at the time of conception. The manufacturer, in
agreement with the European Medicines Agency, has
recommended the following measures while this safety
signal is being evaluated:
.Pregnancy testing should be performed and pregnancy
excluded before initiation of treatment in females of
childbearing potential; effective contraception should
be used throughout treatment;
.Use of dolutegravir should be avoided in pregnancy; if
pregnancy occurs and is confirmed in thefirst
trimester, it is recommended to switch to an
alternative treatment unless there is no suitable
alternative.lINTERACTIONS→Appendix 1 : dolutegravir
lSIDE-EFFECTS
▶Common or very commonDepression.diarrhoea.dizziness
.fatigue.flatulence.gastrointestinal discomfort.
headache.nausea.skin reactions.sleep disorders.
vomiting
▶UncommonArthralgia.hepatitis.hypersensitivity.
immune reconstitution inflammatory syndrome.myalgia.
suicidal tendencies
SIDE-EFFECTS, FURTHER INFORMATION
HypersensitivityHypersensitivity reactions (including
severe rash, or rash accompanied by fever, malaise,
arthralgia, myalgia, blistering, oral lesions, conjunctivitis,
angioedema, eosinophilia, or raised liver enzymes)
reported uncommonly. Discontinue immediately if any
sign or symptoms of hypersensitivity reactions develop.
OsteonecrosisOsteonecrosis has been reported in
patients with advanced HIV disease or following long-term
exposure to combination antiretroviral therapy.
lPREGNANCYManufacturer advises avoid, seeImportant
Safety Information.
lHEPATIC IMPAIRMENTManufacturer advises caution in
severe impairment—no information available.
lPATIENT AND CARER ADVICEPatients or carers should be
given advice on how to administer dolutegravir tablets.
Missed dosesIf a dose is more than 20 hours late on the
once daily regimen (or more than^8 hours late on the twice
daily regimen), the missed dose should not be taken and
the next dose should be taken at the normal time.
lNATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) Decisions
TheScottish Medicines Consortiumhas advised (May 2014 )
that dolutegravir (Tivicay®) is accepted for use within NHS
Scotland when used in combination with other anti-
retroviral medicines for the treatment of HIV infected
adolescents above 12 years. This advice is contingent upon
the continuing availability of the patient access scheme in
NHS Scotland or a list price that is equivalent or lower.
TheScottish Medicines Consortiumhas advised (July
2017 ) that dolutegravir (Tivicay®) is accepted for use
within NHS Scotland when used in combination with other
anti-retroviral medicines for the treatment of HIV infected
children aged 6 to 12 years of age. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
equivalent or lower.
All Wales Medicines Strategy Group (AWMSG) Decisions
TheAll Wales Medicines Strategy Grouphas advised
(October 2017 ) that dolutegravir (Tivicay®)is
recommended as an option for use within NHS Wales in
combination with other anti-retroviral medicinal products
for the treatment of HIV infected patients above 6 years of
age. This recommendation applies only in circumstances
where the approved Wales Patient Access Scheme (WPAS)
is utilised or where the list/contract price is equivalent or
lower than the WPAS price.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Tablet
▶Tivicay(ViiV Healthcare UK Ltd)A
Dolutegravir (as Dolutegravir sodium) 10 mgTivicay 10 mg tablets
| 30 tabletP£ 99. 75
Dolutegravir (as Dolutegravir sodium) 25 mgTivicay 25 mg tablets
| 30 tabletP£ 249. 38
Dolutegravir (as Dolutegravir sodium) 50 mgTivicay 50 mg tablets
| 30 tabletP£ 498. 75
Combinations available:Abacavir with dolutegravir and
lamivudine,p. 416Raltegravir 10-May-2018
lDRUG ACTIONRaltegravir is an inhibitor of HIV integrase.lINDICATIONS AND DOSE
HIV- 1 infection (initiated by a specialist)
▶BY MOUTH USING TABLETS
▶Child (body-weight 25 kg and above): 400 mg twice daily
▶Child (body-weight 40 kg and above): 1200 mg once daily,
once daily dosing for use in patients who are treatment
naive or virologically suppressed on an initial regimen
of 400 mg twice daily—use 600 mg tablets only
▶BY MOUTH USING CHEWABLE TABLETS
▶Child (body-weight 11–13 kg): 75 mg twice daily
▶Child (body-weight 14–19 kg): 100 mg twice daily
▶Child (body-weight 20–27 kg): 150 mg twice daily
▶Child (body-weight 28–39 kg): 200 mg twice daily
▶Child (body-weight 40 kg and above): 300 mg twice daily
▶BY MOUTH USING ORAL SUSPENSION
▶Neonate up to 7 days (body-weight 2 kg): 4 mg once daily.▶Neonate up to 7 days (body-weight 3 kg): 5 mg once daily.
continued→BNFC 2018 – 2019 HIV infection 411
Infection5