Dolutegravir-Lamivudine

Dolutegravir-Lamivudine is a combination medication used to treat the symptoms of HIV Infection. 

• Dolutegravir-Lamivudine is available under the following different brand names: Dovato

Common side effects of Dolutegravir-Lamivudine include:

• Headache,
• Tiredness,
• Nausea,
• Diarrhea, and
• Sleep problems  

Serious side effects of Dolutegravir-Lamivudine include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Fever,
• General ill feelings,
• Tiredness,
• Joint or muscle pain,
• Blisters or mouth sores,
• Redness or swelling in the eyes,
• Blistering or peeling skin,
• Unusual muscle pain,
• Stomach pain,
• Vomiting,
• Fast or irregular heart rate,
• Dizziness,
• Feeling cold,
• Weakness,
• Skin rash (no matter how mild),
• Nausea,
• Loss of appetite,
• Upper stomach pain,
• Dark urine,
• Clay-colored stools,
• Yellowing of the skin or eyes (jaundice),
• Night sweats,
• Swollen glands,
• Cold sores,
• Cough,
• Wheezing,
• Diarrhea,
• Weight loss,
• Trouble speaking,
• Difficulty swallowing,
• Problems with balance or eye movement,
• Prickly feeling,
• Swelling in the neck or throat (enlarged thyroid),
• Menstrual changes, and
• Impotence

Rare side effects of Dolutegravir-Lamivudine include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

HIV Infection

• Adult dosage
  • 1 tablet (.e, dolutegravir 50mg/ lamivudine 300mg) orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, 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.

• Dolutegravir-Lamivudine has severe interactions with the following drugs:
  • dofetilide
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
• Dolutegravir-Lamivudine has serious interactions with at least 25 other drugs.
• Dolutegravir-Lamivudine has moderate interactions with at least 43 other drugs.
• Dolutegravir-Lamivudine has minor interactions with the following drugs:
  • isavuconazonium sulfate
  • sulfamethoxazole
  • zidovudine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to dolutegravir or lamivudine
• Coadministration with dofetilide

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dolutegravir-Lamivudine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dolutegravir-Lamivudine?”

Cautions

• Safety and efficacy of lamivudine have not been established for the treatment of chronic HBV in patients dually infected with HIV-1 and HBV; the emergence of HBV variants associated with resistance to lamivudine reported
• Severe acute HBV exacerbations were reported in patients coinfected with HIV-1 and HBV who have discontinued lamivudine
• Hypersensitivity reactions reported with dolutegravir; reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
• Hepatic adverse events reported with dolutegravir; patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations; in some cases, the elevated transaminases were consistent with immune reconstitution syndrome or HBV reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
• Preliminary data from an observational study suggest dolutegravir is associated with an increased risk of neural tube defects when administered at the time of conception and in early pregnancy
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogs, including lamivudine; female sex and obesity may be risk factors
• Immune reconstitution syndrome
  • Reported in patients treated with combination ARV therapy
  • During the initial phase of combination ARV treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (.g, Mycobacterium avium infection, CMV, Pneumocystis jirovecii pneumonia, or tuberculosis), which may necessitate further evaluation and treatment
  • Autoimmune disorders (.g, Graves disease, polymyositis, and Guillain-Barré syndrome) were also reported; however, the time to onset is more variable and can occur many months after initiation of treatment
• Drug interaction overview
  • Also see Dosage Modifications
  • Dolutegravir: Uridine diphosphate (UDP)-glucuronosyl-transferase (UGT)1A1 substrate (primary); CYP3A4 substrate (minor); also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-GP) in vitro; renal organic cation transporters (OCT)2 inhibitor; multidrug and toxin extrusion transporter (MATE)1 inhibitor
  • Lamivudine: P-gp and BCRP substrate
  • Complete HIV-1 infection treatment regimen; therefore, coadministration with other ARVs not recommended
  • Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (.g, dofetilide [contraindicated], metformin)
  • Drugs that inhibit UGT1A1 and CY3A4 may decrease dolutegravir levels, thereby leading to loss of therapeutic effects and possible development of resistance
  • Coadministration of dolutegravir with polyvalent cation-containing products may decrease dolutegravir absorption
  • Sorbitol decreases lamivudine peak plasma concentration and AUC

Pregnancy and Lactation

• Dolutegravir
  • Based on prospective reports to APR of exposures to dolutegravir during pregnancy resulting in live births (including over 450 exposed in the first trimester and over 280 exposed in the second/third trimester); avoid use at the time of conception through the first trimester owing to the risk of neural tube defects associated with dolutegravir; advise individuals of childbearing potential to consistently use effective contraception; dolutegravir has been shown to cross the placenta
• Lamivudine
  • Based on prospective Antiretroviral Pregnancy Registry (APR) reports (N above 12,000 exposures) resulting in live births (above 5,000 exposed in the first trimester), there was no difference between the overall risk of birth defects for lamivudine compared with the background birth defect rate of 2.7% in the US reference population
  • A pregnancy exposure registry monitors pregnancy outcomes in women during pregnancy; healthcare providers are encouraged to register patients by calling the APR at 1-800-258-4263
  • 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 raltegravir
  • 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 the medicine can cause the HIV infection to worsen
  • Pregnant women stopping dolutegravir-containing regimen without switching to alternative HIV medicines could cause the amount of virus to increase and spread HIV to their baby
  • For patients taking a dolutegravir-containing regimen at the time of becoming pregnant and during the first trimester of pregnancy, there is a potential risk of neural tube defects; neural tube defects happen early in pregnancy before many women even know they are pregnant
  • Inform women of childbearing age about the potential risk of neural tube defects when a dolutegravir-containing regimen is used at the time of conception and early in pregnancy; women of childbearing age should consult their healthcare providers about other non-dolutegravir-containing ARV medicine
  • Healthcare providers should weigh the benefits and the risks of dolutegravir when prescribing antiretroviral medicines to women of childbearing age; consider alternative antiretroviral medicines; discuss the relative risks and benefits of appropriate alternative antiretroviral therapies
  • Women of childbearing age who decide to take a dolutegravir-containing regimen should consistently use effective birth control (contraception) while on HIV treatment; women should discuss with their healthcare professionals an effective birth control method to use while taking a dolutegravir-containing regimen
  • Perform pregnancy testing before initiating a dolutegravir-containing regimen in women of childbearing age to exclude pregnancy
  • Initiation of 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 the feasibility of switching, tolerability, ability to maintain viral suppression, and risk of transmission to infant against the risk of neural tube defects
• Lactation
  • Breastfeeding is not recommended because of the potential for HIV-1 transmission from mother to infant
  • The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed infants to avoid risking postnatal transmission of HIV-1 infection; dolutegravir and lamivudine are present in human milk; there is no information on the effects of the drug components on breastfed infant or effects on milk production
  • Because of the potential for (1) HIV-1 transmission (in HIV-negative infants) and (2) developing viral resistance (in HIV-positive infants), instruct mothers not to breastfeed if they are receiving drug therapy