dolutegravir/lamivudine (Rx)

Brand and Other Names:Dovato
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Dosing & Uses

AdultPediatric

HIV Infection

Indicated as a complete 2-drug regimen for treatment of HIV infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (ie, HIV-1 RNA <50 copies/mL) on a stable ARV regimen and no history of treatment failure and no known substitutions associated with resistance

1 tablet (ie, dolutegravir 50mg/ lamivudine 300mg) PO qDay

Dosage Modifications

Coadministration with carbamazepine or rifampin

  • Dolutegravir dose (ie, 50mg) contained in the combination is insufficient if coadministered with carbamazepine or rifampin
  • If coadministered, take 1 Dovato tablet qDay, followed by an additional dolutegravir 50-mg tablet at ~12 hr from the Dovato dose

Renal impairment

  • CrCl 30-49 mL/min: May experience a 1.6- to 3.3-fold higher lamivudine exposure than patient with a CrCL ≥50 mL/min
  • CrCl <30 mL/min: Not recommended
  • If a dose reduction of lamivudine is required, then use individual components

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment necessary
  • Severe (Child-Pugh C): Not recommended

Dosing Considerations

Tests before initiating

  • Hepatitis B virus (HBV)
  • Pregnancy in women of childbearing potential

Safety and efficacy not established

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Interactions

Interaction Checker

and dolutegravir/lamivudine

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            Contraindicated (2)

            • dofetilide

              dolutegravir will increase the level or effect of dofetilide by decreasing renal clearance. Contraindicated. Dolutegravir inhibits the renal organic cation transporter, OCT2; risk of life-threatening arrhythmias caused by increased systemic exposure to dofetilide

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              lamivudine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.

            Serious - Use Alternative (22)

            • aluminum hydroxide/magnesium carbonate

              aluminum hydroxide/magnesium carbonate will decrease the level or effect of dolutegravir by cation binding in GI tract. Avoid or Use Alternate Drug. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations

            • cabotegravir

              dolutegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

              lamivudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • carbamazepine

              carbamazepine will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • sorbitol

              sorbitol will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Sorbitol-containing solution decreased systemic exposure of lamivudine oral solution in a pediatric study (ARROW trial). Results showed lower rates of virologic suppression, lower plasma lamivudine exposure, and development of viral resistance more frequently than children receiving lamivudine tablets.

            • efavirenz

              efavirenz will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Increase dolutegravir dose to 50 mg BID when coadministered with strong UGT1A/CYP3A inducers

            • etravirine

              etravirine will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Etravirine (a strong UGT1A/CYP3A inducer) significantly reduces dolutegravir plasma concentrations, but the effect of etravirine is mitigated by coadministration of lopinavir/ritonavir or darunavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir; do not use with etravirine without coadministration of atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir

            • fosamprenavir

              fosamprenavir will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Increase dolutegravir dose to 50 mg BID when coadministered with strong UGT1A/CYP3A inducers (eg, fosamprenavir/ritonavir)

            • fosphenytoin

              fosphenytoin will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • magnesium citrate

              magnesium citrate will decrease the level or effect of dolutegravir by cation binding in GI tract. Avoid or Use Alternate Drug. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations

            • magnesium gluconate

              magnesium gluconate will decrease the level or effect of dolutegravir by cation binding in GI tract. Avoid or Use Alternate Drug. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations

            • magnesium oxide

              magnesium oxide will decrease the level or effect of dolutegravir by cation binding in GI tract. Avoid or Use Alternate Drug. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations

            • nevirapine

              nevirapine will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • phenobarbital

              phenobarbital will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • phenytoin

              phenytoin will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • Prussian blue

              Prussian blue will decrease the level or effect of dolutegravir by cation binding in GI tract. Avoid or Use Alternate Drug. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations

            • rifampin

              rifampin will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Increase dolutegravir dose to 50 mg BID when coadministered with strong UGT1A/CYP3A inducers

            • St John's Wort

              St John's Wort will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

            • sucralfate

              sucralfate will decrease the level or effect of dolutegravir by cation binding in GI tract. Avoid or Use Alternate Drug. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations

            • tafenoquine

              tafenoquine will increase the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

            • tipranavir

              tipranavir will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Increase dolutegravir dose to 50 mg BID when coadministered with strong UGT1A/CYP3A inducers (eg, tipranavir/ritonavir)

            • trilaciclib

              trilaciclib will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

            Monitor Closely (43)

            • abacavir

              abacavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • aluminum hydroxide

              aluminum hydroxide will decrease the level or effect of dolutegravir by cation binding in GI tract. Use Caution/Monitor. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations; use alternative therapy if available

            • atazanavir

              atazanavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • cabozantinib

              lamivudine will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity

            • calcium acetate

              calcium acetate will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • calcium carbonate

              calcium carbonate will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • calcium citrate

              calcium citrate will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • dalfampridine

              dolutegravir will increase the level or effect of dalfampridine by Other (see comment). Modify Therapy/Monitor Closely. dolutegravir inhibits OCT2 and multidrug and toxin extrusion transporter 1

            • efavirenz

              efavirenz and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • enfuvirtide

              enfuvirtide and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • erdafitinib

              lamivudine increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of dolutegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dose of dolutegravir to 50 mg PO q12hr for treatment naïve or treatment experienced INSTI-naïve.

            • ferric maltol

              ferric maltol will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • ferrous fumarate

              ferrous fumarate will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • ferrous gluconate

              ferrous gluconate will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • ferrous sulfate

              ferrous sulfate will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • fosamprenavir

              fosamprenavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • ganciclovir

              ganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increased risk of hematologic toxicity.

            • indinavir

              indinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • interferon alfa 2b

              interferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • magnesium hydroxide

              magnesium hydroxide will decrease the level or effect of dolutegravir by cation binding in GI tract. Use Caution/Monitor. Administer dolutegravir 2 hr before or 6 hr after taking medications containing polyvalent cations; use alternative therapy if available

            • magnesium supplement

              magnesium supplement will decrease the level or effect of dolutegravir by Other (see comment). Modify Therapy/Monitor Closely. Drug may form a chelate with polyvalent cations; may decrease absorption by the intestinal tract; applies to oral forms; may administer under fasting conditions 2 hr before administering polyvalent cation or 6 hr after

            • metformin

              dolutegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Dolutegravir inhibits the renal organic cation transporter, OCT2; when used with metformin, limit total daily dose of metformin to 1,000 mg either when starting metformin or dolutegravir; when stopping dolutegravir, adjustment of metformin dose may be necessary; monitor blood glucose when initiating concomitant use and after withdrawal of dolutegravir

            • multivitamins

              multivitamins will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • multivitamins, vision

              multivitamins, vision will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir 2 hr (dolutegravir or abacavir/dolutegravir/lamivudine) or 4 hr (dolutegravir/rilpivirine) before or 6 hr after taking medications containing polyvalent cations.

            • nelfinavir

              nelfinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • nevirapine

              lamivudine and nevirapine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • orlistat

              orlistat will decrease the level or effect of dolutegravir by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

              orlistat will decrease the level or effect of lamivudine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

            • peginterferon alfa 2a

              peginterferon alfa 2a, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • selenium

              selenium will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir at least 2 h before or 6 h after polyvalent cations. Administer the dolutegravir/rilpivirine combination at least 4 h before or 6 h after polyvalent cations.

            • peginterferon alfa 2b

              peginterferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • ribavirin

              ribavirin increases toxicity of lamivudine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of lactic acidosis.

            • ritonavir

              ritonavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • saquinavir

              saquinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of dolutegravir by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer dolutegravir at least 2 hr before or 6 hr after each dose to avoid chelation with magnesium. .

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of dolutegravir by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer dolutegravir at least 2 hr before or 6 hr after each dose to avoid chelation with magnesium. .

            • stavudine

              lamivudine and stavudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • tenofovir DF

              lamivudine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • tipranavir

              tipranavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • trimethoprim

              trimethoprim increases effects of lamivudine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Potential for increased toxicity.

            • valganciclovir

              valganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.

            • zidovudine

              lamivudine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • zinc

              zinc will decrease the level or effect of dolutegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer dolutegravir at least 2 hr before or 6 hr after oral zinc salts.

            Minor (2)

            • sulfamethoxazole

              sulfamethoxazole increases levels of lamivudine by decreasing renal clearance. Minor/Significance Unknown.

            • zidovudine

              lamivudine increases effects of zidovudine by pharmacodynamic synergism. Minor/Significance Unknown. Beneficial synergism.

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            Adverse Effects

            1-10%

            Headache (3%)

            Nausea (2%)

            Diarrhea (2%)

            Insomnia (2%)

            Fatigue (2%)

            <2%

            • Dizziness
            • Blood and lymphatic systems disorders: Anemia, neutropenia, thrombocytopenia
            • Gastrointestinal disorders: Abdominal discomfort, abdominal pain, flatulence, upper abdominal pain, vomiting
            • General: Fever
            • Hepatobiliary disorders: Hepatitis
            • Immune system disorders: Hypersensitivity, immune reconstitution syndrome
            • Musculoskeletal disorders: Myositis
            • Nervous system disorders: Somnolence
            • Psychiatric disorders: Anxiety; abnormal dreams; depression; suicidal ideation, attempt, behavior, or completion; these events were observed primarily with preexisting history of depression or other psychiatric illness
            • Renal and urinary disorders: Renal impairment
            • Skin and subcutaneous tissue disorders: Pruritus, rash

            <1%

            Hypersensitivity reactions

            Postmarketing Reports

            Body as a whole: Redistribution/accumulation of body fat

            Endocrine and metabolic: Hyperglycemia

            General: Weakness

            Hemic and lymphatic: Anemia, including pure red blood cell aplasia and severe anemias progressing on therapy

            Hepatic and pancreatic: Lactic acidosis and hepatic steatosis pancreatitis, posttreatment exacerbations of HBV

            Hepatobiliary disorders: Acute liver failure, hepatotoxicity

            Hypersensitivity: Anaphylaxis, urticaria

            Investigations: Weight increased

            Musculoskeletal: Arthralgia, CPK elevation, muscle weakness, myalgia, rhabdomyolysis

            Nervous system: Paresthesia, peripheral neuropathy

            Skin: Alopecia

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            Warnings

            Black Box Warnings

            All patients with HIV-1 infection should be tested for the presence of hepatitis B virus (HBV) before initiating dolutegravir/lamivudine

            Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens reported

            Severe acute exacerbations of HBV reported in patients who are coinfected with HIV-1 and HBV and have discontinued lamivudine; closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment

            Patients infected with both HIV and HBV should add additional treatment for their hepatitis B or consider a different drug regimen

            Formulations of lamivudine used to treat HIV infection contain a higher dose than formulations indicated for chronic HBV infection

            Contraindications

            Hypersensitivity to dolutegravir or lamivudine

            Coadministration with dofetilide

            Cautions

            Safety and efficacy of lamivudine have not been established for treatment of chronic HBV in patients dually infected with HIV-1 and HBV; emergence of HBV variants associated with resistance to lamivudine reported

            Severe acute HBV exacerbations 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 antihepatitis therapy was withdrawn

            Preliminary data from an observational study suggest dolutegravir is associated with 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 analogues, including lamivudine; female sex and obesity may be risk factors

            Immune reconstitution syndrome

            • Reported in patients treated with combination ARV therapy
            • During initial phase of combination ARV treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, CMV, Pneumocystis jirovecii pneumonia, or tuberculosis), which may necessitate further evaluation and treatment
            • Autoimmune disorders (eg, Graves disease, polymyositis, and Guillain-Barré syndrome) 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 (eg, dofetilide [contraindicated], metformin)
            • Drugs that inhibit UGT1A1 and CY3A4 my 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
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            Pregnancy

            Pregnancy

            Dolutegravir

            Based on prospective reports to APR of exposures to dolutegravir during pregnancy resulting in live births (including over 450 exposed in first trimester and over 280 exposed in second/third trimester); avoid use at time of conception through first trimester owing to risk of neural tube defects associated with dolutegravir; advise individuals of childbearing potential to consistently use effective contraception

            Lamivudine

            Based on prospective Antiretroviral Pregnancy Registry (APR) reports (N >12,000 exposures) resulting in live births (>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 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 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 about 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 feasibility of switching, tolerability, ability to maintain viral suppression, and risk of transmission to infant against risk of neural tube defects

            Lactation

            Breastfeeding is not recommended because of 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; unknown whether drug is present in human breast milk, affects human milk production, or has effects on breastfed infant; when administered to lactating rats, dolutegravir was present in milk

            Because of 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

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Dolutegravir: Integrase strand transfer inhibitor (INSTI); inhibits catalytic activity of HIV-1 integrase, an HIV-encoded enzyme required for viral replication

            Lamivudine: NRTI; following phosphorylation, inhibits HIV reverse transcriptase by viral DNA chain termination; cytosine analog

            Absorption

            Peak plasma time

            • Dolutegravir: 2.5 hr
            • Lamivudine: 1 hr

            Peak plasma concentration

            • Dolutegravir: 3.67 mcg/mL
            • Lamivudine: 2.04 mcg/mL

            Trough plasma concentration

            • Dolutegravir: 1.11 mcg/mL
            • Lamivudine: 0.042 mcg/mL

            AUC

            • Dolutegravir: 53.6 mcg·hr/mL
            • Lamivudine: 8.87 mcg·hr/mL

            Distribution

            Protein bound

            • Dolutegravir: ~99%
            • Lamivudine: 36%

            Metabolism

            Dolutegravir: UGT1A1 (primary); CYP3A (minor)

            Lamivudine: Not significantly metabolized

            Elimination

            Half-life

            • Dolutegravir: ~14 hr
            • Lamivudine: 13-19 hr

            Excretion

            • Dolutegravir: 31% urine; 64% feces
            • Lamivudine: ~70% urine
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            Administration

            Oral Administration

            May take with or without food

            Missed dose: Instruct patients to take a missed dose as soon as they remember, but do not double their next dose or take more than prescribed

            Storage

            Store below 30°C (86°F)

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.