Absolute Contraindications

Do not use dolutegravir in patients with:

Hypersensitivity: Known hypersensitivity to dolutegravir or any excipients in the formulation
Dofetilide: Concurrent use with dofetilide (antiarrhythmic agent) - risk of QT prolongation and serious cardiac arrhythmias

Major Drug Interactions

Drugs That Decrease Dolutegravir Levels

Drug/Class	Mechanism	Clinical Significance	Management
Rifampicin	Strong UGT1A1 inducer	Reduces dolutegravir levels by ~50%	Increase dolutegravir to 50 mg twice daily
Phenytoin, Carbamazepine, Phenobarbital	CYP3A4 and UGT1A1 induction	May reduce dolutegravir levels significantly	Consider 50 mg twice daily; monitor levels
St. John's Wort	UGT1A1 and CYP3A4 induction	Reduces dolutegravir levels	Avoid concurrent use or use 50 mg twice daily
Etravirine	UGT1A1 induction	May reduce dolutegravir levels	Monitor clinical response; consider dosage adjustment

Drugs That Increase Dolutegravir Levels

Drug/Class	Mechanism	Clinical Significance	Management
Ritonavir	CYP3A4 inhibition	May increase dolutegravir levels	No dose adjustment; monitor for adverse effects
Cobicistat	CYP3A4 inhibition	May increase dolutegravir levels	No dose adjustment; monitor for adverse effects
Atazanavir	CYP3A4 inhibition	Modest increase in dolutegravir levels	No dose adjustment needed

Antacids and Mineral Supplements

Important: Dolutegravir absorption is significantly reduced by polyvalent cations (aluminum, magnesium, calcium, iron).

Affected Medications

Antacids containing aluminum or magnesium hydroxide
Calcium supplements and calcium-containing products
Iron supplements and iron-containing products
Multivitamins containing these minerals

Management Strategy

Timing: Take dolutegravir 2 hours BEFORE or 6 hours AFTER antacids/supplements
Alternative: Use antacids that don't contain polyvalent cations (e.g., famotidine, omeprazole)
Monitoring: Monitor for loss of virologic response if timing cannot be maintained

Other Important Drug Interactions

Antiretroviral Agents

NRTIs (Nucleoside/Nucleotide RTIs): No significant interactions; can be used together
NNRTIs (Non-nucleoside RTIs): No major interactions with most agents
Protease Inhibitors: No dose adjustment needed; can be used together
Other INSTIs: No significant interactions

Cardiovascular Drugs

Dofetilide: CONTRAINDICATED - risk of QT prolongation
Other antiarrhythmics: Use with caution; monitor QT interval
Statins: No significant interactions
ACE inhibitors/ARBs: No significant interactions

Antimicrobial Agents

Azithromycin: No significant interactions
Fluoroquinolones: No significant interactions
Antifungals (azoles): No major interactions
Antiretrovirals: See above

Other Drugs

Metformin: No significant interactions
Oral contraceptives: No significant interactions
Warfarin: Monitor INR; no dose adjustment usually needed
NSAIDs: No significant interactions

Adverse Reactions

Very Common (≥1/10)

Headache
Nausea
Diarrhea

Common (≥1/100 to <1/10)

Fatigue/Tiredness
Insomnia
Dizziness
Vomiting
Abdominal pain
Rash
Elevated liver enzymes (AST, ALT)

Uncommon (≥1/1,000 to <1/100)

Hypersensitivity reactions (including rash, fever, hepatitis)
Severe hepatotoxicity
Severe skin reactions (Stevens-Johnson syndrome, DRESS)
Suicidal ideation or behavior (rare)

Rare (<1/1,000)

Severe hypersensitivity syndrome
Hepatic failure
Severe cutaneous adverse reactions

Special Precautions and Warnings

Hepatic Disease

Use with caution in patients with hepatic impairment
Monitor liver function tests regularly
Increased risk of hepatotoxicity in patients with hepatitis B or C co-infection
Consider therapeutic drug monitoring in severe hepatic impairment

Renal Disease

No dose adjustment needed for mild to moderate renal impairment
Limited data for severe renal impairment; use with caution
Minimal renal elimination; hemodialysis unlikely to be effective

Immune Reconstitution Inflammatory Syndrome (IRIS)

May occur in patients with advanced HIV (CD4 <50 cells/mm³)
Characterized by inflammatory response to opportunistic infections
Manage with NSAIDs or corticosteroids as needed
Continue antiretroviral therapy unless IRIS is severe

Mental Health

Monitor for depression, anxiety, and suicidal ideation
Use with caution in patients with history of mental health disorders
Counsel patients on mental health symptoms

Hypersensitivity Reactions

Discontinue immediately if signs of hypersensitivity develop
Signs include: rash, fever, hepatitis, eosinophilia
Do not rechallenge with dolutegravir after hypersensitivity reaction

Overdose Management

No specific antidote for dolutegravir overdose
Treatment is supportive and symptomatic
Activated charcoal may reduce absorption if given shortly after overdose
Monitor vital signs and clinical status
Hemodialysis unlikely to be effective due to high protein binding (>99%)
Contact poison control center or seek emergency medical care

Recommended Monitoring Parameters

Baseline Assessment

HIV RNA level and CD4+ T-cell count
Liver function tests (AST, ALT, bilirubin)
Renal function (creatinine, eGFR)
Complete blood count
Hepatitis B and C serology

During Treatment

HIV RNA level: 2-4 weeks, then every 3 months
CD4+ T-cell count: Every 3 months initially, then every 6-12 months
Liver function tests: At 2-4 weeks, then every 3-6 months
Renal function: Every 6-12 months
Adherence assessment: At each visit
Mental health screening: At each visit

Special Monitoring

Therapeutic drug monitoring: Consider in special populations (pregnancy, hepatic/renal impairment)
QT interval: If using with other QT-prolonging drugs
Drug interaction monitoring: When adding new medications

For Doctors Resources

SMPC PIL (Patient Information) Clinical Data & Efficacy Dosage & Administration Interactions & Contraindications

⚠️ CONTRAINDICATIONS

✗ Hypersensitivity to dolutegravir
✗ Concurrent dofetilide use

Key Interactions

Separate by 2-6 hours: Antacids, Ca/Fe supplements
Dose adjustment: Rifampicin (50 mg BID)
Monitor: Enzyme inducers

Medical Information

For detailed interaction information or clinical questions, contact our medical team.

Drug Interactions & Contraindications