Dolutegravir

Patients without integrase inhibitor resistance concomitantly taking efavirenz, etravirine (without boosted protease inhibitors), nevirapine, tipranavir/ritonavir, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifampicin, and St. John's wort:
Adult: In combination with other antiretroviral agents: 50 mg bid (as conventional tab) or 30 mg bid (as dispersible or soluble tab).
Child: In combination with other antiretroviral agents: As conventional tab: 6 to <12 years 14-<20 kg: 40 mg bid; ≥20 kg: 50 mg bid. 12 to <18 years ≥20 kg: 50 mg bid. As dispersible tab or soluble tab: ≥4 weeks to 5 months 3-<6 kg: 5 mg bid; 6-<10 kg: 10 mg bid. ≥6 months 6-<10 kg: 15 mg bid; 10-<14 kg: 20 mg bid; 14-<20 kg: 25 mg bid; ≥20 kg: 30 mg bid. Dosage recommendations may vary among individual products and between countries (refer to local guidelines).

Pharmacogenomics:

Dolutegravir is metabolised via glucuronidation primarily by UGT1A1 and to a lesser extent by CYP3A isoenzyme. UGT1A1 gene polymorphism may affect the pharmacokinetic response of dolutegravir in certain patients.

The European Medicines Agency (EMA) and US Food and Drug Administration (FDA) drug labels cited that from a meta-analysis in healthy subjects, individuals with UGT1A1 genotypes conferring poor metabolism had a 32% lower dolutegravir clearance and a 46% higher dolutegravir exposure compared with UGT1A1 normal metabolisers. However, there is no evidence that common polymorphisms in drug-metabolising enzymes change dolutegravir pharmacokinetics to a clinically meaningful extent.

Nevertheless, caution is recommended when using dolutegravir in patients with reduced UGT1A1 activity due to potential increased plasma concentrations. No dosage adjustment or genetic testing before dolutegravir treatment initiation is currently recommended.

Dolutegravir May be taken with or without food. Dispersible/soluble tab: May be swallowed whole (1 at a time) or dispersed in a cup containing 5 mL (for ≤3 tabs) or 10 mL (for 4-6 tabs) of water. Gently swirl the cup for 1-2 minutes until a cloudy mixture with no remaining lumps is formed. May be taken directly from the cup or using the oral syringe provided. Administer within 30 minutes of mixing.

Hypersensitivity. Concomitant use with organic cation transporter 2 substrates with narrow therapeutic index (e.g. dofetilide, pilsicainide, fampridine).

Patient with hepatitis B or C co-infection. UGT1A1 poor metabolisers. Before using in patients with integrase inhibitor resistance, take into account that the efficacy of 50 mg bid dolutegravir is reduced in viral resistance Q148 mutations plus ≥2 additional secondary mutations, including G140A/C/S, E138A/K/T, or L74I. Avoid concomitant use with efavirenz, etravirine (without boosted protease inhibitors), nevirapine, tipranavir/ritonavir, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifampicin, and St. John's wort in patients with documented or suspected resistance to integrase inhibitors. Dolutegravir conventional tab and dispersible or soluble tab are not bioequivalent and not interchangeable on a mg-per-mg basis; when switching formulations, follow the dosing recommendation specific for the new dosage form. Severe renal and hepatic impairment. Children. Pregnancy; breastfeeding is not recommended to avoid transmission of HIV.

Significant: Hepatotoxicity (e.g. increased serum transaminases, hepatitis, acute liver failure), hypersensitivity reactions (e.g. rash, constitutional findings, organ dysfunction), immune reconstitution syndrome (e.g. Graves' disease, autoimmune hepatitis), opportunistic infections; osteonecrosis, particularly in patients with advanced HIV infection or long-term exposure to combination antiretroviral therapy; increased weight, increased blood glucose or lipid levels.
Blood and lymphatic system disorders: Neutropenia.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, flatulence, abdominal pain or discomfort.
General disorders and administration site conditions: Fatigue.
Investigations: Increased creatine phosphokinase.
Metabolism and nutrition disorders: Hyperglycaemia.
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Insomnia, depression, anxiety, abnormal dreams.
Skin and subcutaneous tissue disorders: Pruritus.

PO: B

This drug may cause dizziness, if affected, do not drive or operate machinery.

Obtain LFTs at baseline and periodically during treatment. Monitor viral load, CD4 count, and lipid profile. Assess for signs and symptoms of hypersensitivity and hepatotoxicity.

May increase the plasma concentration of fampridine, which increases the risk of seizures. Decreased plasma levels and therapeutic effect with etravirine (without boosted protease inhibitors), efavirenz, nevirapine, tipranavir/ritonavir, fosamprenavir/ritonavir, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, and rifampicin. Increases plasma concentration of metformin. Reduced absorption and plasma levels when given with magnesium- or aluminium-containing antacids or laxatives, iron or calcium supplements (including in multivitamins), and sucralfate. Increased plasma concentrations with atazanavir or atazanavir/ritonavir.
Potentially Fatal: May increase the plasma concentration of dofetilide and pilsicainide, which increases the risk of serious adverse effects.

Food, particularly high-fat meals, slows the rate and increases the extent of absorption. May decrease the serum levels with St. John's wort.

May result in false elevation of serum creatinine by inhibiting tubular secretion of creatinine without affecting actual renal glomerular function.

Description:
Mechanism of Action: Dolutegravir, an antiretroviral agent, is an inhibitor of HIV integrase. It binds to the integrase active site and blocks the strand transfer step of HIV-1 DNA integration, which is necessary for the HIV replication cycle.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Food, particularly high-fat meals, slows the rate and increases the extent of absorption. Time to peak plasma concentration: 1-3 hours.
Distribution: Present in CSF and male or female genital tracts. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 17-20 L. Plasma protein binding: >99%.
Metabolism: Metabolised via glucuronidation primarily by UGT1A1 and to a lesser extent by CYP3A isoenzyme.
Excretion: Mainly via faeces (53% as unchanged drug); urine (31% as metabolites, <1% as unchanged drug). Elimination half-life: Approx 14 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 54726191, Dolutegravir. https://pubchem.ncbi.nlm.nih.gov/compound/Dolutegravir. Accessed July 28, 2025.

Store between 15-30°C. Protect from moisture.

Antivirals

J05AJ03 - dolutegravir ; Belongs to the class of integrase inhibitors. Used as direct acting antiviral in the systemic treatment of viral infections.

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