What to Know About Tivicay (Dolutegravir)

Tivicay (dolutegravir) is an antiretroviral drug used to treat HIV in adults and older children. Licensed for use by the Food and Drug Administration (FDA) in 2013, Tivicay is included in the list of preferred agents used for the first-line treatment of HIV.

Tivicay belongs to a class of drugs called integrase inhibitors that work by blocking an enzyme called integrase that the virus uses to "hijack" the genetic machinery of a cell. By doing so, HIV cannot make copies of itself and is quickly suppressed to undetectable levels.

There are no generic versions of Tivicay.

Uses

Tivicay is used to treat HIV in adults and children 12 and over who weigh at least 66 pounds (30 kilograms). It can be used to treat newly infected people as well as those who have experienced treatment failure.

Tivicay is never prescribed on its own. Instead, it is used as a part of combination antiretroviral therapy with at least one other antiretroviral of another class.

Tivicay cannot cure HIV but, with proper use, can prevent disease progression and reduce the risk of serious HIV-associated illnesses.

Before Taking

Before prescribing Tivicay or any other antiretroviral drug, your healthcare provider will order blood tests to "profile" your virus and determine which drugs are most effective in achieving viral suppression. These include:

• Genetic resistance testing, which identifies the types and numbers of mutations that confer resistance
• Phenotypic testing, which directly exposes the virus to the different antiretroviral drugs to see which work best

Even if you are newly infected or have never taken any antiretroviral drugs, it is possible to contract a drug-resistant virus through sex, shared needles, or other modes of transmission. Genetic and phenotypic testing helps select the drugs best able to overcome these variants.

Precautions and Contraindications

Tivicay is contraindicated for use in people who have had a prior hypersensitive reaction to dolutegravir.

Tivicay should be used with caution in people with hepatitis B, hepatitis C, and other forms of liver disease due to the risk of hepatotoxicity (liver poisoning). If used, routine liver function tests (LFTs) should be performed.

Other Integrase Inhibitors

In addition to Tivicay, there are two other integrase inhibitors approved for use by the FDA:

• Isentress (raltegravir)
• Vocabria (cabotegravir)

The FDA has also approved an injectable therapy called Cabenuva (cabotegravir + rilpivirine) that only requires monthly or every-two-month dosing.

Side Effects

Tivicay and other integrase inhibitors are less likely to cause side effects than many of their earlier-generation counterparts. Even so, the drug has been known on rare occasions to cause severe and potentially life-threatening reactions in some people.

Common

Most of the side effects from Tivicay tend to be mild and resolve within a week or two as your body adapts to treatment. The most common include (by order of frequency):

• Insomnia (3% of users)
• Fatigue (2% of users)
• Headache (2% of users)
• Depression (1% of users)

Other side effects, including dizziness, nausea, diarrhea, and abnormal dreams, occur in less than 1% of users.

Always advise your healthcare provider about any side effects you experience while on Tivicay, particularly if they persist or worsen.

Severe

Although rare, severe side effects have been reported in users of Tivicay. Some occur with weeks of starting treatment, while others are associated with ongoing use. These include:

• Drug hypersensitivity: Typically occurring within four to six weeks of starting treatment, symptoms can be serious and may involve a severe rash, fever, body aches, blistering skin, facial swelling, hepatitis, and difficulty breathing.
• Hepatotoxicity: Typically experienced in people with pre-existing liver disease, symptoms may include abdominal swelling, extreme fatigue, nausea, vomiting, dark urine, and jaundice.
• Immune reconstitution inflammatory syndrome (IRIS): This is a paradoxical reaction in which antiretroviral therapy triggers an immune overreaction or "unmasks" an undiagnosed infection like tuberculosis, typically in people with a low CD4 count.

Dosages

Tivicay is available in three tablet formulations that allow for the modification of doses when needed:

• 50-milligram tablets: A yellow, round, film-coated pill embossed with "SV 572" on one side and "50" on the other
• 25-milligram tablets: A pale yellow, round, film-coated pill embossed with "SV 572" on one side and "25" on the other
• 10-milligram tablets: A white, round, film-coated pill embossed with "SV 572" on one side and "10" on the other

The recommended dose for adults and children can vary by weight as well as the results of genetic testing.

Modifications

The concentration of Tivicay in the blood can be reduced when taken with certain medications (see "Drug Interactions" below).

These include a large class of drugs called cytochrome P450 (CYP450) inducers that rely on the same enzyme for metabolization as Tivicay. The competition for the enzyme can cause dolutegravir levels to drop, reducing its efficacy.

The same can occur with another class of drugs called uridine 5′-diphospho-glucuronosyltransferase 1A (UGT1A) inducers.

To compensate for this, the once-daily dose would be increased to twice-daily to better sustain the optimal therapeutic concentration.

How to Take and Store

Tivicay can be taken with or without food. The pills should be swallowed whole; do not chew, crush, or split the pills as this can affect drug absorption.

Tivicay can be stored safely at room temperature, ideally around 77 degrees F (25 degrees C). Keep the pills in their original light-resistant container, and avoid storing them on a sunny windowsill or in your glove compartment. Discard any pills that have expired.

Warnings and Interactions

Tivicay can be used safely in pregnancy. This contrasts with earlier concerns about the drug that led the FDA in 2019 to temporarily remove it from the list of preferred first-line agents.

Several smaller studies published in 2018 and 2019 had suggested that Tivicay could cause neural tube birth defects if taken during the first trimester. The studies, involving a total of 11 cases in Botswana and Rwanda, were later found to be associated with folate deficiency. rather than any effects of dolutegravir. In response, the FDA reinstated Tivicay's preferred status in February 2021.

Even so, there is a lack of well-controlled studies investigating the long-term safety of Tivicay in pregnancy. If you are pregnant or in your child-bearing years, speak with your healthcare provider to fully understand the benefits and risks of treatment.

Breastfeeding is not recommended in women with HIV irrespective of their treatment status.

Drug Interactions

Tikosyn (dofetilide), a drug used to treat cardiac arrhythmia (irregular heartbeat), is contraindicated for use with Tivicay. Taking the drugs together can increase the concentration of dofetilide in the blood and may induce a serious and potentially life-threatening arrhythmia.

Other interactions can affect the concentration of Tivicay in the blood, including the aforementioned CYP450 and UGT1A inducers. In some cases, the interaction can be overcome by adjusting the dose or taking the medications several hours apart. Other interactions require a drug substitution.

Among the interactions of special concern are:

• Antiretroviral drugs: Intelence (etravirine), Sustiva (efavirenz), Viramune (nevirapine), as well as the combination of Aptivus (tipranavir) and Norvir (ritonavir)
• Anticonvulsants: Dilantin (phenytoin), Luminal (phenobarbital), Tegretol (carbamazepine), Trileptal (oxcarbazepine), and others
• Calcium supplements
• Glucophage (metformin)
• Iron supplements
• Tuberculosis drugs: Mycobutin (rifabutin), Priftin (rifapentine), Rifadin (rifampin), and others
• St. John's wort