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Warning: Posttreatment Acute Exacerbation of Hepatitis B Virus (HBV)<\/strong><\/p>\n\n\n\n<\/div>\n\n\n\n
All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV been reported in people with concomitant HIV-1 and HBV who have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1<\/span> and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted.<\/strong><\/p>\n\n\n\n<\/div>\n\n\n\n
Selected Safety Information<\/strong><\/p>\n\n\n\n<\/div>\n\n\n\n
DELSTRIGO is contraindicated when coadministered<\/span> with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John\u2019s wort (Hypericum perforatum<\/em>)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO.<\/p>\n\n\n\n<\/div>\n\n\n\n
DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine.<\/p>\n\n\n\n
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Warnings and Precautions<\/strong><\/p>\n\n\n\n<\/div>\n\n\n\n
Severe Skin Reactions<\/strong><\/em><\/p>\n\n\n\nSevere skin reactions, including Stevens-Johnson syndrome (SJS)\/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue DELSTRIGO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated.<\/p>\n\n\n\n
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New or Worsening Renal Impairment<\/strong><\/em><\/p>\n\n\n\nRenal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in people living with HIV with risk factors for renal dysfunction who appeared stable on TDF.<\/p>\n\n\n\n
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Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL\/min.<\/span><\/p>\n\n\n\n<\/div>\n\n\n\n
Bone Loss and Mineralization Defects<\/strong><\/em><\/p>\n\n\n\nIn clinical trials in HIV-1 infected adults, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults are unknown.<\/p>\n\n\n\n
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Immune Reconstitution Syndrome<\/strong><\/em><\/p>\n\n\n\nImmune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment.<\/p>\n\n\n\n
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Drug Interactions<\/strong><\/p>\n\n\n\nBecause DELSTRIGO is a complete regimen, co-administration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.<\/p>\n\n\n\n
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Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions.<\/p>\n\n\n\n
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If coadministered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine approximately 12 hours after the dose of DELSTRIGO.<\/p>\n\n\n\n
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Dosage and Administration\/Specific Populations<\/strong><\/p>\n\n\n\n<\/div>\n\n\n\n
Renal Impairment<\/strong><\/em><\/p>\n\n\n\nBecause DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL\/min.<\/p>\n\n\n\n
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Adverse Reactions<\/strong><\/p>\n\n\n\nThe most common adverse reactions with DELSTRIGO (incidence \u22655%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%).<\/p>\n\n\n\n
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By week 96 in DRIVE-AHEAD, 3% of adult participants in the DELSTRIGO group and 7% in the efavirenz (EFV)\/emtricitabine (FTC)\/TDF group had adverse events leading to discontinuation of study medication.<\/p>\n\n\n\n
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In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C)<\/span> were pre-specified. LDL-C: -2.1 mg\/dL<\/span> in the DELSTRIGO group vs 8.3 mg\/dL<\/span> in the EFV\/FTC\/TDF group. Non-HDL-C:<\/span> -4.1 mg\/dL<\/span> in the DELSTRIGO group vs 12.7 mg\/dL<\/span> in the EFV\/FTC\/TDF group. The clinical benefits of these findings have not been demonstrated.<\/p>\n\n\n\n<\/div>\n\n\n\n
In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified<\/span> categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult participants in the DELSTRIGO group and 26% in the EFV\/FTC\/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV\/FTC\/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV\/FTC\/TDF group reported altered sensorium.<\/p>\n\n\n\n<\/div>\n\n\n\n
The safety of DELSTRIGO in virologically-suppressed<\/span> adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult participants was similar to that in participants with no ARV treatment history.<\/p>\n\n\n\n<\/div>\n\n\n\n
In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C<\/span> were pre-specified<\/span>. LDL-C: -16.3 mg\/dL<\/span> in the DELSTRIGO group vs -2.6 mg\/dL<\/span> in the PI + ritonavir group. Non-HDL-C:<\/span> -24.8 mg\/dL<\/span> in the DELSTRIGO group vs -2.1 mg\/dL<\/span> in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated.<\/p>\n\n\n\n<\/div>\n\n\n\n
Pregnancy\/Breastfeeding<\/strong><\/p>\n\n\n\nThere is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.<\/p>\n\n\n\n
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Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1\u2013negative infants), (2) developing viral resistance (in HIV-1\u2013positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults.<\/p>\n\n\n\n
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Specific Populations<\/strong><\/p>\n\n\n\n<\/div>\n\n\n\n
Hepatic Impairment<\/em><\/strong><\/p>\n\n\n\nNo dosage adjustment is necessary for patients with mild to moderate hepatic impairment. DELSTRIGO has not been studied in patients with severe hepatic impairment<\/p>\n\n\n\n
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What is the mechanism of action for DELSTRIGO?<\/strong><\/h4><\/summary>DELSTRIGO is a three-drug combination of doravirine, lamivudine, and tenofovir disoproxil fumarate.<\/span>\n<\/div>\n\n\n\n
Doravirine: <\/strong>Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). The inhibitory concentration at 50% (IC50) of doravirine for RNA-dependent DNA polymerization of recombinant wild-type HIV-1 RT in a biochemical assay was 12.2\u00b12.0 nM (n=3). Doravirine does not inhibit the human cellular DNA polymerases \u03b1, \u03b2, and mitochondrial DNA polymerase \u03b3.<\/p>\n\n\n\n<\/div>\n\n\n\n
Lamivudine: <\/strong>Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5\u00b4-triphosphate<\/span> metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. Lamivudine triphosphate (3TC-TP) is a weak inhibitor of mammalian DNA polymerases \u03b1, \u03b2, and mitochondrial DNA polymerase \u03b3.<\/p>\n\n\n\n<\/div>\n\n\n\n
Tenofovir disoproxil fumarate (TDF): <\/strong>TDF is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. TDF requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5\u2032-triphosphate<\/span> and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases \u03b1, \u03b2, and mitochondrial DNA polymerase \u03b3.<\/p>\n\n\n\n<\/div>\n\n\n\n
Acronyms<\/strong><\/h3><\/div>\n\n\n\n<\/div>\n\n\n\n
DNA, deoxyribonucleic acid; RNA, ribonucleic acid.<\/p>\n<\/div><\/details><\/div>\n\n\n\n
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What drug class does DELSTRIGO belong to?<\/strong><\/h4><\/summary>DELSTRIGO is a combination of three antiretroviral drugs. Doravirine is an NNRTI (non-nucleoside reverse transcriptase inhibitor) and lamivudine and tenofovir disoproxil fumarate are NRTIs (nucleoside\/nucleotide reverse transcriptase inhibitors).<\/span><\/div><\/details><\/div>\n\n\n\ndefault-sum-open-background-color<\/div>
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