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 ?
It integrates Dolutegravir, and Emtricitabine and Tenofovir Alafenamide, which in turn are the individual drugs that constitute ViiV Healthcare's Tivicay and Gilead Sciences' Descovy, respectively.
The FDA's tentative approval of Mylan's Dolutegravir, Emtricitabine, and Tenofovir Alafenamide Tablets sets a new standard for affordable access for patients in countries hardest hit by HIV, as it's the first time a product combines dolutegravir and tenofovir alafenamide," said Mylan CEO Heather Bresch.
Based on the fundamental principle that no one should have to take more medicines than necessary, ViiV Healthcare has put in place a comprehensive two-drug regimen research and development program built around the characteristics of dolutegravir," commented John Pottage, chief scientific and medical officer for ViiV.
Currently dolutegravir (DTG) in combination with either abacavir (ABC) or rilpivirine (RPV) and the investigational integrase inhibitor cabotegravir (CAB) in combination with RPV are being studied in 2-drug regimens.
Amongst the last group, dolutegravir was incorporated in October 2015 for 3rd line treatment of HIV/AIDS.
Three of the ongoing studies are designed to explore the safety and efficacy of BIC/FTC/TAF compared to triple-therapy regimens containing dolutegravir in treatment-naive patients and virologically suppressed patients switching from an existing antiretroviral regimen with dolutegravir.
dolutegravir for treatment of HIV infection, in response to the most recent evidence showing the medicine's safety, efficacy, and high barrier to resistance;
Approuve pour la premiere fois aux Etats-Unis en 2013, le Dolutegravir (DTG) a ete envoye a plus de 20000 patients au Kenya, avec le soutien d'Unitaid, une organisation internationale d'achats de medicaments.
Finally, one study assigned lopinavir /ritonavir (LPV/r) as the third medication and one more randomized assignment with the entire treatment schedule ABC/3TC plus dolutegravir (DTG) or TDF/FTC plus EFV.
And the integrase inhibitors dolutegravir, (42) elvitegravir, (43) and raltegravir (42,43) seem even more lipid-friendly.
Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression.
Dolutegravir is generally well-tolerated with minimal adverse effects ([greater than or equal to] 2% incidence of headache and insomnia) and toxicity.