Chemical: Drug
dolutegravir
PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.
1. Annotation of FDA Label for dolutegravir and UGT1A1
Summary
The FDA-approved drug label for TIVICAY (dolutegravir) states that subjects with UGT1A1 genotypes that result in poor metabolism of the drug have decreased clearance and increased AUC as compared to those who have UGT1A1 genotypes that result in normal dolutegravir metabolism. The label does not mention specific UGT1A1 variants or genetic testing.
Annotation
Dolutegravir is indicated for the treatment of HIV-1 infection, in combination with other antiretroviral agents. Excerpts from the dolutegravir drug label:
Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A.
Polymorphisms in Drug-Metabolizing Enzymes: In a meta-analysis of healthy subject trials, subjects with UGT1A1 (n = 7) genotypes conferring poor dolutegravir metabolism had a 32% lower clearance of dolutegravir and 46% higher AUC compared with subjects with genotypes associated with normal metabolism via UGT1A1 (n = 41).
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the dolutegravir drug label.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
Genes and/or phenotypes found in this label
-
ABCB1
- other, Drug interactions section
- source: U.S. Food and Drug Administration
-
ABCG2
- other, Drug interactions section
- source: U.S. Food and Drug Administration
-
SLC22A2
- other, Drug interactions section
- source: U.S. Food and Drug Administration
-
SLC22A6
- other, Drug interactions section
- source: U.S. Food and Drug Administration
-
SLC22A8
- other, Drug interactions section
- source: U.S. Food and Drug Administration
-
SLC47A1
- other, Drug interactions section
- source: U.S. Food and Drug Administration
-
UGT1A1
- metabolism/PK, Drug interactions section, Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
UGT1A3
- metabolism/PK, Drug interactions section
- source: U.S. Food and Drug Administration
-
UGT1A9
- other, Drug interactions section
- source: U.S. Food and Drug Administration
PharmGKB contains no Clinical Variants that meet the highest level of criteria.
Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.
The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.
The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.
The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.
Links in the "Gene" column lead to PharmGKB Gene Pages.
List of all variant annotations for dolutegravir
| Gene ? |
Variant?
(147) |
Alternate Names ? | Chemicals ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|---|
VA
|
UGT1A1 | *1 | N/A | N/A | N/A | ||
|
VA
|
UGT1A1 | *6 | N/A | N/A | N/A | ||
|
VA
|
UGT1A1 | *28 | N/A | N/A | N/A | ||
|
VA
|
UGT1A1 | *36 | N/A | N/A | N/A | ||
|
VA
|
UGT1A1 | *37 | N/A | N/A | N/A |
Overview
PharmGKB Accession Id
PA166114961
Type(s):
Drug
Other Vocabularies
- RxNorm: dolutegravir (1433868)
Information pulled from DrugBank has not been reviewed by PharmGKB.
Chemical Properties
SMILES
C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O
Source: PubChem
InChI String
InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1
Source: PubChem
Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.
Curated Information ?
Curated Information ?
| Evidence | Disease |
|---|---|
|
|
HIV |
Publications related to dolutegravir: 3
|
|
Effect of carbamazepine on dolutegravir pharmacokinetics and dosing recommendation. European journal of clinical pharmacology. 2016. Song Ivy, et al.
|
|
|
Population pharmacokinetics of dolutegravir in HIV-infected treatment-naive patients. British journal of clinical pharmacology. 2015. Zhang Jianping, et al.
|
| Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics. Pharmacogenomics. 2014. Chen Shuguang, et al.
|
LinkOuts
- PubChem Compound:
- Dolutegravir (54726191)
Clinical Trials
These are trials that mention dolutegravir and are related to either pharmacogenetics or pharmacogenomics.
NURSA Datasets
No NURSA datasets available.