dolutegravir

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

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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

‡Depends on concurrent use of metabolic inducers.

Contraind./Precautions ⬆ ⬇

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.

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

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 rifampinmay ↓ levels and effectiveness; ↑ dose of dolutegravir.
Nevirapine may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of metformin.
Oxcarbazepine, phenobarbital, phenytoinmay ↓ 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 wortmay ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

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

PO (Adults ): Treatment-naïve or treatment-experienced INSTI-naïve patients or virologically suppressed (HIV RNA <50 copies/mL) patients switching to dolutegravir plus rilpivirine: 50 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve 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-naïve or treatment-experienced INSTI-naïve patients: Tivicay PD: 30 mg once daily; Tivicay tablets: 50 mg once daily Treatment-naïve or treatment-experienced INSTI-naïve 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-naïve or treatment-experienced INSTI-naïve patients: Tivicay PD (preferred): 25 mg once daily; Tivicay tablets: 40 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve 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-naïve or treatment-experienced INSTI-naïve patients: Tivicay PD: 20 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve 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-naïve or treatment-experienced INSTI-naïve patients: Tivicay PD: 15 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve 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-naïve or treatment-experienced INSTI-naïve patients: Tivicay PD: 5 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin: Tivicay PD: 5 mg twice daily.

Availability ⬆ ⬇

(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]

Assessment ⬆ ⬇

Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Monitor for signs and symptoms of hypersensitivity reactions (rash, fever, malaise, fatigue, muscle or joint aches, blisters or peeling of skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Discontinue therapy and do not restart.

Lab Test Considerations:

Monitor viral load and CD4 counts regularly during therapy.
- Verify negative pregnancy test before starting therapy.
- May cause ↓ ANC, hemoglobin, total neutrophils, and platelet counts.
- Monitor liver function periodically during therapy. May cause ↑ serum glucose, lipase, AST, ALT, total bilirubin, CK concentrations.

Implementation ⬆ ⬇

PO: May be administered without regard to food.
- Tablets for oral suspension are preferred for patients weighing <20 kg. DNC: Administer by swallowing tablets for oral suspension whole; do not crush, break, cut, or chew. Tablets for oral suspension may also be dispersed in 5 mL (for 1 or 3 tablets for oral suspension or 10 mL (for 4–6 tablets for oral suspension) of drinking water. Disperse in cup provided, swirl suspension so no lumps remain. After dispersion, administer within 30 min of mixing.
- Administer 2 hrs before or 6 hrs after calcium and iron supplements.

Patient/Family Teaching ⬆ ⬇

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.

Evaluation/Desired Outcomes ⬆ ⬇

Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
Decrease in viral load and improvement in CD4 cell counts.

US Brand Names ⬆ ⬇

Code ⬆

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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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇