Dosing and uses of Tivicay (dolutegravir)
Adult dosage forms and strengths
tablet
- 50mg
HIV Infection
Integrase strand transfer inhibitor (INSTI) indicated in combination with other ARTs for treatment of HIV-1 infection
Treatment-naïve or treatment-experienced INSTI-naïve: 50 mg PO qDay
INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: 50 mg PO BId
Dosage modifications
Treatment-naïve or treatment-experienced INSTI-naïve when coadministration with potent UGT1A/CYP3A inducers (eg, efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, rifampin): Increase dose to 50 mg PO BId
Mild-to-moderate hepatic impairment (Child-Pugh A or B): No dosage adjustment required
Severe hepatic impairment (Child-Pugh C): Not recommended
Renal impairment
- Plasma concentrations were decreased in subjects with severe renal impairment
- No dosage adjustment required for treatment-naïve or treatment-experienced and INSTI-naïve patients with mild, moderate, or severe renal impairment or for INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance) with mild or moderate renal impairment
- Severe renal impairment in for INSTI-experienced patients with resistance: Not recommended; decrease in dolutegravir concentrations may result in loss of therapeutic effect and development of resistance
Dosing Considerations
Poor virologic response was observed in subjects treated with TIVICAY 50 mg BID with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions, including L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/r
In patients with underlying hepatitis B or C, measure hepatic enzymes before initiating therapy and periodically thereafter
Pediatric dosage forms and strengths
tablet
- 10mg
- 25mg
- 50mg
HIV Infection
Indicated in combination with other ARTs for treatment-naïve or treatment-experienced INSTI-naïve children weighing at least 30 kg
<30 kg: Safety and efficacy not established
≥30 kg to <40 kg: 35 mg PO qDay (ie, one 25-mg tablet and one 10-mg tablet)
≥40 kg: 50 mg PO qDay
Dosage modifications
Treatment-naïve or treatment-experienced INSTI-naïve when coadministration with potent UGT1A/CYP3A inducers (eg, efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, rifampin): Increase weight-based dose to twice daily
Dosing Considerations
Safety and efficacy have not been established in pediatric patients weighing <30 kg or in pediatric patients who are INSTI-experienced with documented or clinically suspected resistance to other INSTIs (ie, raltegravir, elvitegravir)
Tivicay (dolutegravir) adverse (side) effects
>10%
Increased cholesterol and triglycerides (up to 17%)
1-10%
Increased lipase (1-8%)
Hyperglycemia (<1-7%)
Increased creatinine kinase (3-4%)
Increased AST (2-3%)
Insomnia (<1-3%)
Increased ALT (2%)
Increased bilirubin (<1-2%)
Headache (<1-2%)
GI disorders (<2%)
Fatigue (<2%)
Hepatitis (<2%)
Myositis (<2%)
Renal impairment (<2%)
Pruritus (<2%)
Nausea (<1-1%)
<1%
Abnormal dreams
Dizziness
Diarrhea
Rash
Vertigo
Warnings
Contraindications
Coadministration with dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events
Cautions
Hypersensitivity reactions reported; characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” observed
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy; may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis) or autoimmune disorders (eg, Graves’ disease, polymyositis, and Guillain-Barre’ syndrome)
Inducers of UGT1A1 and CYP3A (eg, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St John’s wort, rifampin) decrease dolutegravir
Coadministration with medications containing polyvalent cations decrease dolutegravir systemic exposure; give dolutegravir 2 hr before or 6 hr after polyvalent cations (eg, antacids, laxatives, sucralfate, iron supplements, calcium supplements, buffered medications)
Pregnancy and lactation
Pregnancy category: B
Antiretroviral pregnancy registry: 1-800-258-4263
Lactation: Unknown if distributed in human breast milk
The CDC recommends that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tivicay (dolutegravir)
Mechanism of action
Integrase strand transfer inhibitor (INSTI); inhibits catalytic activity of HIV-1 integrase, an HIV encoded enzyme required for viral replication
Absorption
Peak plasma time: 2-3 hr
Peak plasma concentration: 3.67-4.15 mcg/mL
AUC 53.6-75.1 mcg•h/mL
Distribution
Protein bound: ≥98.9%
Vd: 17.4 L; 4-232 ng/mL (CSF)
Metabolism
Metabolized by UGT1A1 with some contribution from CYP3A
Elimination
Half-life: 14 hr
Clearance: 1 L/hr
Excretion: 53% feces (unchanged); 31% urine (as ether glucuronide, benzylic carbon, or N-dealkylation product); <1% urine (unchanged)
Administration
Oral Administration
May take with or without food
