dolutegravir

REMS

HIV-1 infection (in combination with other antiretrovirals).
HIV-1 infection in patients to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for 6 mo with no history of treatment failure or known substitutions associated with resistance to either dolutegravir or rilpivirine (in combination with rilpivirine).

Contraindicated in:

Concurrent use of dofetilide
Severe hepatic impairment
OB: Avoid use through first trimester of pregnancy
Lactation: Breastfeeding not recommended in mothers with HIV.

Use Cautiously in:

Underlying hepatic disease, including hepatitis B or C (↑ risk of hepatotoxicity)
End-stage renal disease requiring dialysis
OB: Can consider use during second or third trimester of pregnancy if potential maternal benefit justifies potential fetal risk
Rep: Women of reproductive potential
Pedi: Children <4 wk, <3 kg, or INSTI-experienced with resistance documented to other INSTIs (safety and effectiveness not established)
Geri: Consider age-related ↓ in cardiac, renal and hepatic function, chronic disease states and concurrent medications in older adults.

Derm: pruritus.

GI: HEPATOTOXICITY (↑ WITH HEPATITIS B OR C).

GU: renal impairment.

MS: myositis.

Neuro: headache, insomnia, fatigue.

Misc: hypersensitivity reactions (including rash, constitutional symptoms, and liver injury), immune reconstitution syndrome.

Drug-Drug:

May ↑ levels and risk of toxicity of dofetilide; concurrent use contraindicated.
Etravirine may ↓ levels and effectiveness; should not be used concurrently without atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir).
Efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, and rifampin may ↓ levels and effectiveness; ↑ dose of dolutegravir.
Nevirapine may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of metformin.
Oxcarbazepine, phenobarbital, phenytoin may ↓ levels and effectiveness; avoid concurrent use.
Cation-containing antacids or laxatives, as well as buffered medications, or sucralfate may ↓ absorption and effectiveness; dolutegravir should be taken 2 hr before or 6 hr after these medications.
Calcium supplements (oral) or iron supplements (oral) may ↓ absorption and effectiveness; under fasting conditions, dolutegravir should be taken 2 hr before or 6 hr after these medications; when taken with food, dolutegravir and calcium or iron supplements may be taken at the same time.
May ↑ dalfampridine levels and risk of seizures.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

(Generic available)

Tablets (Tivicay): 10 mg; 25 mg; 50 mg;
Tablets for oral suspension (Tivicay PD): 5 mg;
In combination with: abacavir and lamivudine (Triumeq, Triumeq PD); lamivudine (Dovato); rilpivirine (Juluca). See Appendix [not included in this PDA edition]

Tablets (Tivicay) and tablets for oral suspension (Tivicay PD) are not interchangeable.

PO (Adults): Treatment-nave or treatment-experienced INSTI-nave patients or virologically suppressed (HIV RNA <50 copies/mL) patients switching to dolutegravir plus rilpivirine: 50 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: 50 mg twice daily; INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance (consider other combinations that do not include metabolic inducers): 50 mg twice daily.
PO (Children 20 kg): Treatment-nave or treatment-experienced INSTI-nave patients: Tivicay PD: 30 mg once daily; Tivicay tablets: 50 mg once daily Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 25 mg twice daily; Tivicay tablets: 50 mg twice daily.
PO (Children 14–<20 kg): Treatment-nave or treatment-experienced INSTI-nave patients: Tivicay PD (preferred): 25 mg once daily; Tivicay tablets: 40 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin: Tivicay PD (preferred): 25 mg twice daily; Tivicay tablets: 40 mg twice daily.
PO (Children 10–<14 kg): Treatment-nave or treatment-experienced INSTI-nave patients: Tivicay PD: 20 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 20 mg twice daily.
PO (Children 4 wk and 6–<10 kg): Treatment-nave or treatment-experienced INSTI-nave patients: Tivicay PD: 15 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 15 mg twice daily.
PO (Children 4 wk and 3–<6 kg): Treatment-nave or treatment-experienced INSTI-nave patients: Tivicay PD: 5 mg once daily; Treatment-nave or treatment-experienced INSTI-nave patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 5 mg twice daily.

Inhibits HIV-1 integrase, which is required for viral replication.

Therapeutic Effects:

Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: integrase strand transfer inhibitors (INSTI)

Absorption: Bioavailability is unknown.

Distribution: Enters CSF.

Protein Binding: >98.9%.

Metabolism/Excretion: Metabolized primarily by the UGT1A1 enzyme system with some metabolism by the CYP3A4 isoenzyme. 53% excreted unchanged in feces. Metabolites are renally excreted, minimal renal elimination of unchanged drug. Poor UGT1A1 metabolizers have ↑ dolutegravir concentrations and an ↑ risk of adverse effects.

Half-life: 14 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–3 hr	12–24 hr†

†Depends on concurrent use of metabolic inducers.

Emphasize the importance of taking dolutegravir as directed. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered unless within 4 hr of next dose; then skip dose. Do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx renewal in case of changes.
Instruct patient that dolutegravir should not be shared with others.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Inform patient that dolutegravir does not cure AIDS or prevent associated or opportunistic infections. Dolutegravir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of dolutegravir are unknown at this time.
Advise patient to notify health care professional if signs and symptoms of hypersensitivity occur.
Advise patient to notify health care professional if signs and symptoms of immune reconstitution syndrome (signs and symptoms of an infection) occur.
Rep: May cause fetal harm. Neural tube defects have occurred when administered in first trimester. Advise females of reproductive potential to use effective contraception during first trimester and to notify health care professional if pregnancy is planned or suspected. May be considered during the second and third trimesters of pregnancy if the expected benefit justifies the potential risk to the pregnant woman and the fetus. Avoid breastfeeding during therapy. Enroll pregnant patients in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

NDC Code^*

49702- ViiV Healthcare Company
49702-226- Tivicay 49702-226-13- 30 TABLET, FILM COATED in 1 BOTTLE (49702-226-13)

49702- ViiV Healthcare Company
49702-227- Tivicay 49702-227-13- 30 TABLET, FILM COATED in 1 BOTTLE (49702-227-13)

49702- ViiV Healthcare Company
49702-228- Tivicay 49702-228-13- 30 TABLET, FILM COATED in 1 BOTTLE (49702-228-13)

50090- A-S Medication Solutions
50090-1355- Tivicay 50090-1355-0- 30 TABLET, FILM COATED in 1 BOTTLE (50090-1355-0)

50090- A-S Medication Solutions
50090-1355- Tivicay 50090-1355-1- 5 TABLET, FILM COATED in 1 BOTTLE (50090-1355-1)

53808- DOH CENTRAL PHARMACY
53808-1130- Tivicay 53808-1130-1- 30 TABLET, FILM COATED in 1 BLISTER PACK (53808-1130-1)

70518- REMEDYREPACK INC.
70518-1487- Tivicay 70518-1487-0- 30 TABLET, FILM COATED in 1 BLISTER PACK (70518-1487-0)

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