dolutegravir


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Related to dolutegravir: rilpivirine, cobicistat

dolutegravir

(doe-loo-teg–ra-vir ) ,

Tivicay

(trade name)

Classification

Therapeutic: antiretrovirals
Pharmacologic: integrase strand transfer inhibitors
Pregnancy Category: B

Indications

Treatment of HIV-1 infection, in combination with other antiretrovirals

Action

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.

Pharmacokinetics

Absorption: Absorption follows oral administration; bioavailability is unknown
Distribution: Enters CSF
Protein Binding: >98.9%
Metabolism and Excretion: Metabobolized primarily by the UGT1A1 enzyme system with some metabolism by CYP3A4. 53% excreted unchanged in feces. Metabolites are renally excreted, minimal renal elimination of unchanged drug. genetic implication Poor metabolizers of dolutegravir have ↑ levels and ↓ clearance.
Half-life: 14 hr

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunk2–3 hr12–24 hr†
†Depends on concurrent use of metabolic inducers

Contraindications/Precautions

Contraindicated in: Concurrent use of dofetilide;Severe hepatic impairment; Lactation: Breast feeding not recommended in HIV-infected patients.
Use Cautiously in: Underlying hepatic disease, including hepatitis B or C (↑ risk fo hepatotoxicity);Severe renal impairment; Geriatric: Consider age-related decrease in cardiac, renal and hepatic function, chronic disease states and concurrent medications; Obstetric: Use during pregnancy only if clearly needed; Pediatric: Patients <12 yr, <49 kg or INSTI-experienced (have received raltegravir or elvitegravir) or resistance documented (safety and effectiveness not established).

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • insomnia (most frequent)
  • fatigue

Gastrointestinal

  • hepatic toxicity (↑ with hepatitis B or C)

Genitourinary

  • renal impairment

Dermatologic

  • pruritus

Metabolic

  • fat accumulation/redistribution

Musculoskeletal

  • myositis

Miscellaneous

  • hypersensitivity reactions (including rash, constitutional symptoms, and liver injury)
  • immune reconstitution syndrome

Interactions

Drug-Drug interaction

Blood levels and effectiveness are ↓ by etravirine (should not be used concurrently without atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir).Blood levels and effectiveness are ↓ by efavirenz, dosage adjustment is recommended.Blood levels and effectiveness may be↓ by nevirapine Blood levels and effectiveness are ↓ by fosamprenavir/ritonavir or tipranavir/ritonavir ; dosage adjustment is recommended.May ↑ blood levels and toxicity from dofetilide (arrhythmias) or metformin (hypoglycemia), concurrent dofetilide should be avoided.Blood levels and effectiveness may be ↓ other metabolic inducers including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or rifampin ; concurrent use should be avoided and alternative medications considered.Absorption and effectiveness may be ↓ by cation-containing antacids, buffered medications, calcium supplements (oral), iron supplements (oral), laxatives, or sucralfate ; dolutegravir should be taken 2 hr before or 6 hr after.Blood levels and effectiveness may be ↓ St. John's wort ; concurrent use should be avoided.

Route/Dosage

Oral (Adults) Treatment-naïve or treatment-experienced INSTI-naïve patients—50 mg once daily; Treatment-naïve or treatment-experienced INSTI-naïve patients currently receiving efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir 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.
Oral (Children ≥ 12 yr and >40 k g) 50 mg once daily; concurrent efavirenz, fosamprenavir/ritonavir, tipranvir/ritonavir or rifampin—50 mg twice daily.

Availability

Tablets: 50 mg

Nursing implications

Nursing 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.
    • May casue ↓ ANC, hemoglobin, total neutrophils, and platelet counts.
    • May cause ↑ serum glucose, lipase, AST, ALT, total bilirubin, creatine kinase concentrations.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: May be administered without regard to food.

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 sheet before starting therapy and with each prescription renewal in case changes have been made.
  • 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.
  • Inform patient that dolutegravir does not cure AIDS or prevent associated or opportunistic infections. Dolutegravir does not 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 or infection occur.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • Advise patients to notify health care professional if pregnancy is planned or suspected. Breast feeding should be avoided during therapy. Pregnant patients should be encouraged to enroll 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.
References in periodicals archive ?
Today's positive opinion takes us a step closer to bringing physicians and people living with HIV a dolutegravir based regimen that can be taken once-daily as a single-tablet," said Dr John Pottage, Chief Scientific and Medical Officer, ViiV Healthcare.
ViiV Healthcare submitted a Marketing Authorisation Application (M) for dolutegravir to the European Medicines Agency (EMA) on 17 December, 2012.
Today's announcement follows the US Food and Drug Administration (FDA) approval of dolutegravir (Tivicay) on 12 August 2013 and the European Medicines Agency (EMA) approval on 20 January 2014.
The dolutegravir clinical development programme involved more than 2,500 people living with HIV.
SAILING (ING111762) is an ongoing Phase III, multicentre, double blind, double dummy study to compare the efficacy and safety of dolutegravir 50mg once-daily to raltegravir 400mg twice-daily in treatment-experienced, integrase inhibitor-naive adults with HIV-1.
Dolutegravir and other suspect agents should be discontinued immediately if signs or symptoms of hypersensitivity reactions develop.
Prespecified secondary analyses also supported non-inferiority of dolutegravir to raltegravir; the proportion of subjects without treatment-related discontinuations was 93% on dolutegravir and 92% on raltegravir.
Cabotegravir is an investigational integrase strand inhibitor (INSTI) and analogue of dolutegravir (TIVICAY[sup.
There are no data yet on changes in BMD with dolutegravir, but bone turnover marker findings are encouraging.
Estos farmacos reducen la secrecion tubular de la creatinina; ademas la rilpivirina y dolutegravir bloquean la absorcion de la creatinina de la sangre, inhibiendo el transportador de cationes organicos, y el cobicistat interactua con el flujo de salida de la inhibicion de multiples farmacos.
RGV has a low resistance barrier and if patients fail this drug it should be discontinued to prevent resistance to the second-generation integrase inhibitor dolutegravir (DTG).
New integrase inhibitors like the daily-dosed dolutegravir are not yet available in SA, and the local price is as yet unknown.