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Dolutegravir

Brand Name and Other Names: Tivicay

Generic Name: Dolutegravir

Drug Class: HIV, Integrase Inhibitors

What Is Dolutegravir Used For and How Does it Work?

Dolutegravir is used to treat HIV infection.

Dolutegravir is available under the following different brand names: Tivicay.

What Are Dosages of Dolutegravir?

Dosages of Dolutegravir:

Tablet

Pediatric Dosage Forms and Strengths

Tablet

  • 10 mg
  • 25 mg
  • 50 mg
Dosage Considerations – Should be Given as Follows:

HIV Infection

Indicated in combination with other ARTs in adults

  • Integrase strand transfer inhibitor (INSTI) indicated in patients who weigh 30 kg or greater
  • Treatment-naïve or treatment-experienced INSTI-naïve: 50 mg orally once daily
  • INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance: 50 mg orally twice daily

Indicated in combination with other ARTs for treatment-naïve or treatment-experienced INSTI-naïve children who weigh 30 kg or greater.

  • Less than 30 kg: Safety and efficacy not established
  • 30 kg to 40 kg: 35 mg orally once daily (i.e., one 25-mg tablet and one 10-mg tablet)
  • 40 kg and greater: 50 mg orally once daily

Indicated in combination with rilpivirine for adults

  • To replace the current ART regimen in virologically suppressed patients (HIV-1 RNA less than 50 copies/mL) on a stable ART regimen 6 months or more with no history of treatment failure or known substitutions associated with resistance to dolutegravir or rilpivirine
  • 50 mg orally once daily

Dosage Modifications

Administration with potent UGT1A/CYP3A inducers

  • Treatment-naïve or treatment-experienced INSTI-naïve when administered with potent UGT1A/CYP3A inducers (e.g., efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, rifampin)
  • Adults: Increase dose to 50 mg orally twice daily
  • Pediatric patients: Increase the weight-based dose to twice daily

Hepatic impairment

  • Mild-to-moderate hepatic impairment (Child-Pugh A or B): No dosage adjustment is required
  • Severe hepatic impairment (Child-Pugh C): Not recommended

Renal impairment

  • Plasma concentrations were decreased in subjects with severe renal impairment
  • No dosage adjustment is 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 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 twice daily 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
  • Safety and efficacy have not been established in pediatric patients weighing less than 30 kg or in pediatric patients who are INSTI-experienced with documented or clinically suspected resistance to other INSTIs (i.e., raltegravir, elvitegravir)

What Are Side Effects Associated with Using Dolutegravir?

Side effects of Dolutegravir may include.

Less common side effects of dolutegravir include:

Postmarketing side effects of dolutegravir reported include:

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

What Other Drugs Interact with Dolutegravir?

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe interactions of dolutegravir include:

  • dofetilide

Serious interactions of dolutegravir include:

Moderate interactions of dolutegravir include:

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What Are Warnings and Precautions for Dolutegravir?

Warnings

This medication contains dolutegravir. Do not take Tivicay if you are allergic to dolutegravir or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

  • Documented hypersensitivity
  • Coadministration with dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events

Effects of Drug Abuse

  • No information available.

Short-Term Effects

  • See "What Are Side Effects Associated with Using Dolutegravir?"

Long-Term Effects

  • See "What Are Side Effects Associated with Using Dolutegravir?"

Cautions

  • Hypersensitivity reactions reported; characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
  • Hepatic adverse events reported; patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations; in some cases, transaminase elevations were consistent with immune reconstitution syndrome or hepatitis B reactivation particularly in the setting where antihepatitis therapy was withdrawn
  • Hepatic toxicity, including elevated serum liver biochemistries, hepatitis, and acute liver failure reported without pre-existing hepatic disease or other identifiable risk factors; drug-induced liver injury leading to liver transplant reported; monitoring for hepatotoxicity recommended
  • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy; may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis) or autoimmune disorders (eg, Graves’ disease, polymyositis, and Guillain-Barre’ syndrome)
  • May 18, 2018: The FDA issued a safety alert regarding the potential risk of neural tube birth defects

Drug interaction overview

  • Coadministration with certain drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect and possible resistance, or significant adverse reactions of other from increase systemic exposure
  • Inducers of UGT1A1 and CYP3A (e.g., oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St John's wort, rifampin) decrease dolutegravir
  • Coadministration with medications containing polyvalent cations decrease dolutegravir systemic exposure; give dolutegravir 2 hours before or 6 hours after polyvalent cations (e.g., antacids, laxatives, sucralfate, iron supplements, calcium supplements, buffered medications)
  • Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (dofetilide and metformin)

Pregnancy and Lactation

A pregnancy exposure registry monitors pregnancy outcome in women who use dolutegravir during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

There are insufficient human data on dolutegravir use during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Given the limited number of pregnancies exposed to dolutegravir-based regimens reported to APR, no definitive conclusions can be drawn on safety in pregnancy, and continued monitoring is ongoing through the APR.

Initiation of dolutegravir therapy is not recommended in individuals actively trying to become pregnant unless there is no suitable alternative. A benefit-risk assessment should consider factors such as feasibility of switching, tolerability, ability to maintain viral suppression, and risk of transmission to infant against risk of neural tube defects.

In animal reproduction studies with dolutegravir, no evidence of adverse developmental outcomes was observed during organogenesis.

Potential risk of neural tube birth defects

  • Serious cases of neural tube birth defects involving the brain, spine, and spinal cord were reported in babies born to women treated with dolutegravir.
  • Preliminary results from an ongoing observational study in Botswana found women who had received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for these defects; to date, in this observational study there are no reported cases of babies born with neural tube defects to women starting dolutegravir later in pregnancy.
  • Recommendations
    • Patients should not discontinue dolutegravir without consulting a healthcare professional because stopping your medicine can cause the HIV infection to worsen.