December 2019 new listings wrap-up

Dolutegravir 50 mg + lamivudine 300 mg fixed-dose combination (FDC) tablets (Dovato) have been listed on the PBS as Authority Required (Streamlined) on the S100 - Highly Specialised Drugs Program (Community Access) for the treatment of HIV infection in adults and adolescents.^1,2

What is it?

Dolutegravir is an integrase strand transfer inhibitor (INSTI) that prevents HIV replication by stopping HIV DNA from integrating into the nucleus of the host cell.^3,4

Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits viral DNA synthesis to prevent replication of the HIV virus.⁵

Who is it for?

Dolutegravir + lamivudine FDC is TGA-approved for the treatment of HIV infection in adults and adolescents (from 12 years of age and weighing at least 40 kg) who are antiretroviral treatment-naïve and have no known or suspected resistance to either antiretroviral component. It is not approved for treatment-experienced individuals with HIV.³

According to the clinical criteria for PBS-listing, for initial treatment individuals must be antiretroviral treatment-naïve and must not have suspected resistance to either dolutegravir or lamivudine.¹

For continuing treatment, individuals must have previously received PBS-subsidised treatment with this medicine for HIV infection.¹

For grandfathered treatment, for individuals to transition from concomitant dolutegravir and lamivudine to the FDC², they must have previously received non-PBS subsidised treatment with this medicine for HIV before 1 December 2019 and be antiretroviral treatment-naïve before starting on this medicine.¹

Safety issues

Compared to treatment with the individual medicines in the FDC (in conjunction with other antiretroviral medicines), the adverse effects seen with the FDC were found to be generally consistent.³

Dolutegravir + lamivudine FDC should not be prescribed in individuals that may require dose adjustments (eg, creatinine clearance less than 50 mL/min).³

Dolutegravir has been associated with an increased risk of neural tube defects in infants. 

Dolutegravir is not recommended for women who are:⁶ 

• pregnant and within 12 weeks post-conception
• of childbearing potential, sexually active, and not using effective contraception
  
• contemplating pregnancy.

For women who are using effective contraception, use of a dolutegravir-based medicine can be considered after discussing the risks and benefits of this drug with the patient.⁶

Lactic acidosis and severe hepatomegaly with steatosis (including cases of fatalities) have been reported with use of treatment regimens containing lamivudine.³ Pancreatitis (and worsening of existing pancreatitis) has also been reported.⁵

Use of dolutegravir + lamivudine FDC with metformin may result in increased metformin plasma concentrations.³

Additionally, there is potential for drug interactions between dolutegravir + lamivudine FDC and etravirine, efavirenz, nevirapine, tipranavir/ritonavir, carbamazepine, phenytoin, phenobarbital, St John’s wort and rifampicin.³

Dolutegravir + lamivudine FDC should be administered two hours before or six hours after taking polyvalent cation-containing antacids or supplements containing calcium, magnesium or iron. Alternatively, if dolutegravir + lamivudine FDC is taken with food, calcium, magnesium or iron supplements may be taken at the same time.^3,5

See the dolutegravir + lamivudine FDC (Dovato) product information for more information about these drug interactions.

Other items listed in December 2019 include:

• carmellose sodium for severe dry eye syndrome (General Schedule, Items 11852T, 11853W)
• hypromellose for severe dry eye syndrome (General Schedule, Items 11842G, 11849P)
• sevelamer for hyperphosphataemia (General Schedule, Item 11856B)
• dolutegravir + abacavir + lamiduvine for HIV infection, restriction level changed to include <12 years old (Highly Specialised Drugs Program (Community Access), Item 10345L) 

See the PBS Summary of Changes for a complete list of all additions, deletions and alterations.