Dovato (dolutegravir/lamivudine) for HIV: Side Effects & Dosage

Generic drug: dolutegravir and lamivudine

Brand name: Dovato

What is Dovato (dolutegravir and lamivudine), and how does it work?

Dovato (dolutegravir and lamivudine) is a prescription medicine that is used without other antiretroviral medicines to treat HIV-1 infection in adults:

who have not received antiretroviral medicines in the past, and
without known resistance to the medicines dolutegravir or lamivudine.

HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).

It is not known if Dovato is safe and effective in children.

What are the side effects of Dovato?

WARNING

PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HUMAN IMMUNODEFICIENCY VIRUS (HIV-1): EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating
Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If
Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.

Severe acute exacerbations of HBV have been reported in patients who are
co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of
Dovato. Closely monitor hepatic function in these patients and, if appropriate,
initiate anti-HBV treatment.

Dovato can cause serious side effects, including:

Allergic reactions. Call your healthcare provider right away if you develop a rash with
Dovato. Stop taking Dovato and get medical help right away if you develop a rash with any of the following signs or symptoms:
- fever
- generally ill feeling
- tiredness
- muscle or joint aches
- blisters or sores in mouth
- blisters or peeling of the skin
- redness or swelling of the eyes
- swelling of the mouth, face, lips, or tongue
- problems breathing
Liver problems. People with a history of hepatitis B or C virus may have an increased risk of developing new or worsening changes in certain liver tests during treatment with
Dovato. Liver problems, including liver failure, have also happened in people without a history of liver disease or other risk factors. Your healthcare provider may do blood tests to check your liver.

Tell your healthcare provider right away if you get any of the following signs or symptoms of liver problems:

- your skin or the white part of your eyes turns yellow (jaundice)
- dark or “tea-colored” urine
- light-colored stools (bowel movements)
- nausea or vomiting
- loss of appetite
- pain, aching, or tenderness on the right side of your stomach area
Too much lactic acid in your blood (lactic acidosis). Lactic acidosis is a serious medical emergency that can lead to death.
Tell your healthcare provider right away if you get any of the following symptoms that could be signs of lactic acidosis:
- feel very weak or tired
- unusual (not normal) muscle pain
- trouble breathing
- stomach pain with nausea and vomiting
- feel cold, especially in your arms and legs
- feel dizzy or light-headed
- have a fast or irregular heartbeat
Lactic acidosis can also lead to severe liver problems, which can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Tell your healthcare provider right away if you get any of the signs or symptoms of liver problems which are listed above under “Liver problems”. You may be more likely to get lactic acidosis or severe liver problems if you are female or very overweight (obese).
Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after you start taking
Dovato.
The most common side effects of Dovato include:
- headache
- diarrhea
- nausea
- trouble sleeping
- tiredness

These are not all the possible side effects of Dovato. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Dovato?

Testing Prior To Or When Initiating Treatment With Dovato

Prior to or when initiating Dovato, test patients for HBV infection.
Perform pregnancy testing before initiation of Dovato in individuals of
childbearing potential.

Recommended Dosage

Dovato is a fixed-dose combination product containing 50 mg of
dolutegravir and 300 mg of lamivudine. The recommended dosage regimen of
Dovato in adults is one tablet taken orally once daily with or without food.

Recommended Dosage With Certain Coadministered Drugs

The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with drugs listed in Table 1 that may decrease dolutegravir concentrations; the following dolutegravir dosage regimen is recommended.

Table 1. Dosing Recommendations for Dovato with Coadministered Drugs

Coadministered Drug
Dosing Recommendation

Carbamazepine, rifampin
An additional dolutegravir 50-mg tablet, separated by 12 hours from
Dovato, should be taken.

Not Recommended In Patients With Renal Impairment

Because Dovato is a fixed-dose tablet and cannot be dose adjusted,
Dovato is not recommended in patients with creatinine clearance less than 30
mL per minute.

Not Recommended In Patients With Severe Hepatic Impairment

Dovato is not recommended in patients with severe hepatic impairment
(Child-Pugh Score C).

What drugs interact with Dovato?

Coadministration With Other Antiretroviral Drugs

Dovato is a complete regimen for the treatment of HIV-1 infection; therefore,
coadministration with other antiretroviral drugs for the treatment of HIV-1
infection is not recommended. Information regarding potential drug-drug
interactions with other antiretroviral drugs is not provided.

Potential For Dovato To Affect Other Drugs

Dolutegravir, a component of Dovato, inhibits the renal organic cation
transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus,
it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such
as dofetilide, dalfampridine, and metformin.

Potential For Other Drugs To Affect The Components Of Dovato

Dolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 with some contribution from cytochrome P450 (CYP)3A. Dolutegravir is also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp)
in vitro.
Drugs that induce those enzymes and transporters may decrease dolutegravir
plasma concentrations and reduce the therapeutic effect of Dovato.
Coadministration of Dovato and other drugs that inhibit these enzymes may increase dolutegravir plasma concentrations.
Coadministration of dolutegravir with polyvalent cation-containing products
may lead to decreased absorption of dolutegravir.

Established And Other Potentially Significant Drug Interactions

No drug interaction studies were conducted with Dovato. The drug interactions
described are based on studies conducted with dolutegravir or lamivudine when
administered alone. Information regarding potential drug interactions with
Dovato are provided in Table 5.
These recommendations are based on either drug
interaction trials or predicted interactions due to the expected magnitude of
interaction and potential for serious adverse events or loss of efficacy.

Table 5. Established and Other Potentially Significant Drug Interactions for
Dovato: Alterations in Dose May Be Recommended Based on Drug Interaction Trials or Predicted Interactions

Coadministered Drug Class: Drug Name
Effect on Concentration
Clinical Comment

Antiarrhythmic:
Dofetilide
↑Dofetilide
Coadministration is contraindicated with Dovato.

Anticonvulsant:
Carbamazepine^a
↓Dolutegravir
An additional dolutegravir 50-mg dose should be taken, separated
by 12 hours from Dovato.

Anticonvulsants:
Oxcarbazepine
Phenytoin
Phenobarbital
↓Dolutegravir
Avoid coadministration with Dovato because there are insufficient data to make dosing recommendations.

Antidiabetic:
Metformin^a
↑Metformin
Refer to the prescribing information for metformin for assessing the benefit and risk of concomitant use of
Dovato and metformin.

Antimycobacterial:
Rifampin^a
↓Dolutegravir
An additional 50-mg dose of dolutegravir should be taken,
separated by 12 hours from Dovato.

Herbal product:
St. John’s wort (Hypericum perforatum)
↓Dolutegravir
Avoid coadministration with Dovato because there are insufficient data to make dosing recommendations.

Medications containing polyvalent cations (e.g., Mg or Al):
Cation-containing antacids^a or laxatives
Sucralfate Buffered medications
↓Dolutegravir
Administer Dovato 2 hours before or 6 hours after taking medications containing polyvalent cations.

Oral calcium and iron supplements, including multivitamins containing calcium or iron^a
↓Dolutegravir
When taken with food, Dovato and supplements or multivitamins containing calcium or iron can be taken at the same time. Under fasting conditions,
Dovato should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.

Potassium channel blocker:
Dalfampridine
↑Dalfampridine
Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with
Dovato should be considered against the risk of seizures in these patients.

Sorbitol^a
↓Lamivudine
When possible, avoid use of sorbitol-containing medicines with
Dovato.

↑ = Increase, ↓ = Decrease.
^a see prescribing information for magnitude of interaction.

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Is Dovato safe to use while pregnant or breastfeeding?

There are insufficient human data on the use of Dovato during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage.
Data from a birth outcome surveillance study have identified an increased risk of neural tube defects when dolutegravir, a component of
Dovato, is administered at the time of conception compared with non-dolutegravir-containing antiretroviral regimens.
- As defects related to closure of the neural tube occur from conception through the first 6 weeks of gestation, embryos exposed to dolutegravir from the time of conception through the first 6 weeks of gestation are at potential risk.
- In addition, 2 of the 5 birth defects (encephalocele and iniencephaly) that have been observed with dolutegravir use, although often termed neural tube defects, may occur post-neural tube closure, the time period of which may be later than 6 weeks of gestation, but within the first trimester.
- Due to the limited understanding of the types of reported neural tube defects associated with dolutegravir use and because the date of conception may not be determined with precision, an alternative treatment to
  Dovato should be considered at the time of conception through the first trimester of pregnancy.
Initiation of Dovato is not recommended in individuals actively trying to become pregnant unless there is no suitable alternative
The Centers for Disease Control and Prevention recommends that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.
Lamivudine, a component of Dovato, is present in human milk. It is not known whether dolutegravir, a component of
Dovato, is present in human milk.