Abacavir; Dolutegravir; Lamivudine
abacavir-dolutegravir-lamivudine is an antiviral combination for the treatment of HIV-1 infection.
Source:
EMA
Active Ingredients:
Indications
Representation
Inaccurate sex representation in patient population
Efficacy
No sex-specific efficacy data
Posology
No sex differences in posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
43.8-47.6%
52.4-56.2%
Clinical study participation by sex
0-87%
13-100%
Representation Gap
Inaccurate sex representation
-47.6% to +43.2%
-43.2% to +47.6%
Sex-specific efficacy/accuracy
No sex-specific data
In SINGLE, week-48 HIV-1 RNA <50 copies/mL was 88% in males.
In SINGLE, week-48 HIV-1 RNA <50 copies/mL was 85% in females; ARIA evaluated the regimen in adult women.
Sex-specific posology
No sex differences in data
No sex-specific data were reported in the evaluated sources.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Pregnancy / lactation
N / A
The medication can be used during pregnancy if clinically needed. Large datasets for dolutegravir, abacavir and lamivudine individually indicate no malformative or feto/neonatal toxicity, while data for the triple combination are limited; during lactation, dolutegravir and abacavir are excreted in human milk and lamivudine infant exposure is very low, and women living with HIV are recommended not to breast-feed to avoid HIV transmission.
Sex-specific non-clinical findings
There are no human data on male fertility; animal studies indicated no effects on male fertility.
There are no human data on female fertility; animal studies indicated no effects on female fertility.
Disease prevalence by sex
Men
43.8-47.6%
Women
52.4-56.2%
Clinical study participation by sex
Men
0-87%
Women
13-100%
Representation Gap
Inaccurate sex representation
Men
-47.6% to +43.2%
Women
-43.2% to +47.6%
Sex-specific efficacy/accuracy
No sex-specific data
Men
In SINGLE, week-48 HIV-1 RNA <50 copies/mL was 88% in males.
Women
In SINGLE, week-48 HIV-1 RNA <50 copies/mL was 85% in females; ARIA evaluated the regimen in adult women.
Sex-specific posology
No sex differences in data
No sex-specific data were reported in the evaluated sources.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Pregnancy / lactation
Men
N / A
Women
The medication can be used during pregnancy if clinically needed. Large datasets for dolutegravir, abacavir and lamivudine individually indicate no malformative or feto/neonatal toxicity, while data for the triple combination are limited; during lactation, dolutegravir and abacavir are excreted in human milk and lamivudine infant exposure is very low, and women living with HIV are recommended not to breast-feed to avoid HIV transmission.
Sex-specific non-clinical findings
Men
There are no human data on male fertility; animal studies indicated no effects on male fertility.
Women
There are no human data on female fertility; animal studies indicated no effects on female fertility.
General information
General Efficacy
Primary endpoints: Primary efficacy was based on virologic suppression, defined as HIV-1 RNA <50 copies/mL by Snapshot algorithm at Week 48 in treatment-naïve adult trials. In the switch study, the key endpoint was plasma HIV-1 RNA <50 c/mL at Week 24 with maintenance to Week 48. Secondary endpoints: Important supportive endpoints included median time to viral suppression, change from baseline in CD4+ T-cell count, longer-term virologic suppression at Weeks 96 and 144, subgroup response analyses by baseline factors, and resistance emergence. In paediatric studies, supportive virologic outcomes included HIV-1 RNA <200 copies per mL at Week 48.
General Posology
Film-coated tablets: abacavir-dolutegravir-lamivudine 50 mg/600 mg/300 mg orally once daily in adults, adolescents and children weighing at least 25 kg. Dispersible tablets for children aged at least 3 months and weighing 6 to <25 kg: 6 to <10 kg 15/180/90 mg once daily (3 tablets); 10 to <14 kg 20/240/120 mg once daily (4 tablets); 14 to <20 kg 25/300/150 mg once daily (5 tablets); 20 to <25 kg 30/360/180 mg once daily (6 tablets). If co-administered with strong enzyme inducers, give an additional dolutegravir dose about 12 hours after the fixed-dose product. Oral use; can be taken with or without food; dispersible tablets must be dispersed in drinking water.
Further Dose Adjustments
Use the film-coated tablets only in patients weighing at least 25 kg; if co-administered with strong enzyme inducers, give an additional dolutegravir dose about 12 hours after the fixed-dose product. Contraindicated with OCT2 substrates with narrow therapeutic windows, including fampridine/dalfampridine.
Possible Side Effects
Very common adverse reactions were insomnia, headache, nausea, diarrhoea and fatigue. The most frequently reported reactions were nausea (12%), insomnia (7%), dizziness (6%) and headache (6%). Serious reactions included hypersensitivity reactions, including rash and severe liver effects; very rare erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis; and rare acute hepatic failure.
Contraindications
Hypersensitivity to the active substances or any excipients; co-administration with medicinal products with narrow therapeutic windows that are OCT2 substrates, including fampridine/dalfampridine.
Clinical Trial Type and Population
Efficacy and safety were evaluated in multiple adult treatment-naïve HIV-1 studies and supportive studies. Major adult trials with reported demographics were SINGLE (n=833; median age 35 years; 16% women), SPRING-2 (n=822; median age 37/35 years across arms; 15%/14% women), FLAMINGO (n=485; median age 34/34 years across arms; 13%/17% women), and ARIA (n=499; median age 37 years; 100% women).
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex differences in posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
43.8-47.6%
52.4-56.2%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Sex-specific posology
No sex differences in data
No sex-specific data were reported in the evaluated sources.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Pregnancy / lactation
N / A
No data on use in pregnancy or lactation were identified in the available sources. Decisions on treatment should follow official prescribing information and clinical guidelines.
Sex-specific non-clinical findings
There are no human data on male fertility; animal studies indicated no effects on male fertility.
There are no human data on female fertility; animal studies indicated no effects on female fertility.
Disease prevalence by sex
Men
43.8-47.6%
Women
52.4-56.2%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Sex-specific posology
No sex differences in data
No sex-specific data were reported in the evaluated sources.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Pregnancy / lactation
Men
N / A
Women
No data on use in pregnancy or lactation were identified in the available sources. Decisions on treatment should follow official prescribing information and clinical guidelines.
Sex-specific non-clinical findings
Men
There are no human data on male fertility; animal studies indicated no effects on male fertility.
Women
There are no human data on female fertility; animal studies indicated no effects on female fertility.
General information
General Efficacy
Primary endpoints: Primary efficacy was based on virologic suppression, defined as HIV-1 RNA <50 copies/mL by Snapshot algorithm at Week 48 in treatment-naïve adult trials. In the switch study, the key endpoint was plasma HIV-1 RNA <50 c/mL at Week 24 with maintenance to Week 48. Secondary endpoints: Important supportive endpoints included median time to viral suppression, change from baseline in CD4+ T-cell count, longer-term virologic suppression at Weeks 96 and 144, subgroup response analyses by baseline factors, and resistance emergence. In paediatric studies, supportive virologic outcomes included HIV-1 RNA <200 copies per mL at Week 48.
General Posology
Film-coated tablets: abacavir-dolutegravir-lamivudine 50 mg/600 mg/300 mg orally once daily in adults, adolescents and children weighing at least 25 kg. Dispersible tablets for children aged at least 3 months and weighing 6 to <25 kg: 6 to <10 kg 15/180/90 mg once daily (3 tablets); 10 to <14 kg 20/240/120 mg once daily (4 tablets); 14 to <20 kg 25/300/150 mg once daily (5 tablets); 20 to <25 kg 30/360/180 mg once daily (6 tablets). If co-administered with strong enzyme inducers, give an additional dolutegravir dose about 12 hours after the fixed-dose product. Oral use; can be taken with or without food; dispersible tablets must be dispersed in drinking water.
Further Dose Adjustments
For children aged at least 3 months and weighing 6 to <25 kg, use weight-band dispersible tablets; if co-administered with strong enzyme inducers, give an additional dolutegravir dose about 12 hours after the fixed-dose product. Contraindicated with OCT2 substrates with narrow therapeutic windows, including fampridine/dalfampridine.
Possible Side Effects
Very common adverse reactions were insomnia, headache, nausea, diarrhoea and fatigue. The most frequently reported reactions were nausea (12%), insomnia (7%), dizziness (6%) and headache (6%). Serious reactions included hypersensitivity reactions, including rash and severe liver effects; very rare erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis; and rare acute hepatic failure.
Contraindications
Hypersensitivity to the active substances or any excipients; co-administration with medicinal products with narrow therapeutic windows that are OCT2 substrates, including fampridine/dalfampridine.
Clinical Trial Type and Population
Efficacy and safety were evaluated in multiple adult treatment-naïve HIV-1 studies and supportive studies. Major adult trials with reported demographics were SINGLE (n=833; median age 35 years; 16% women), SPRING-2 (n=822; median age 37/35 years across arms; 15%/14% women), FLAMINGO (n=485; median age 34/34 years across arms; 13%/17% women), and ARIA (n=499; median age 37 years; 100% women).
EQUAL CARE® Evaluations
EQUAL CARE® Evaluation
Medication
Source
Source:
EMA
Date of first authorisation:
1st September 2014
Source URL:
Prevalence Source: