Names and pronunciation
(doe-loo-teg′ra-vir) Tivicay, Tivicay PD
Source page 411
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Individual generic drug information
Extracted information for dolutegravir only.
(doe-loo-teg′ra-vir) Tivicay, Tivicay PD
Source page 411
Func. class.: Antiretroviral Func. class.: Antiretroviral/antiviral
Source pages 411, 412
ACTION: Inhibits catalytic activity of HIV integrase, which is an HIV-encoded enzyme needed for replication ACTION: Dolutegravir/lamivudine is active against infections caused by human immunodeficiency virus type 1 (HIV-1). Lamivudine is a nucleoside analog that works by inhibiting HIV reverse transcrip- tase, while dolutegravir works by inhibit- ing the catalytic activity of HIV integrase
Source pages 411, 412
USES: HIV in combination with other antiretrovirals USES: HIV-1 infection in adults
Source pages 411, 413
Chem. class.: INST/NRTI
Source page 412
Extracted information for dolutegravir only.
CONTRAINDICATIONS: Breast- feeding, hypersensitivity Precautions: Pregnancy, children, geriatric patients, hepatic disease, immune reconstitution syndrome, hep- atitis, antimicrobial resistance, lactase deficiency CONTRAINDICATIONS: Hyper- sensitivity Precautions: Alcoholism, autoimmune disease, bone fractures, breastfeeding, children, depression, females, Graves’ disease, Guillain-Barré syndrome, hepatic disease, hepatitis, hepatitis B and HIV coinfection, hepatitis C and HIV coinfection, hepatomegaly, HIV resis- tance, hypercholesterolemia, hyperlipid- emia, hypertriglyceridemia, hypophos- phatemia, immune reconstitution syndrome, lactic acidosis, obesity, osteo- malacia, osteoporosis, pregnancy, renal failure, renal impairment, serious rash, suicidal ideation, torsades de pointes
Source pages 411, 413
SIDE EFFECTS CNS: Fatigue, headache, insomnia GI: Nausea, vomiting, diarrhea, hepatotoxicity INTEG: Rash, pruritus META: Hyperglycemia SYST: Immune reconstitution syndrome GU: Renal dysfunction SIDE EFFECTS CNS: Headache, abnormal dreams, depres- sion, dizziness, insomnia, neuropathy, par- esthesia, asthenia, fatigue, drowsiness GI: Nausea, vomiting, anorexia, diar- rhea, abdominal pain, dyspepsia, hepa- tomegaly with stenosis (may be fatal), hyperbilirubinemia, hypercholesterolemia, pancreatitis GU: Glomerulonephritis membranous/ mesangial proliferative D INTEG: Rash, skin discoloration MS: Arthralgia, myalgia, rhabdomyolysis RESP: Cough SYST: Change in body fat distribution, lactic acidosis
Source pages 412, 413
INTERACTIONS Decrease: effect of dolutegravir—antac- ids, laxatives/sucralfate, oral iron, oral calcium, buffered products Decrease: levels—rifAMPin efavirenz, tenofovir, tipranavir/ritonavir Drug/Herb • Avoid concurrent use with St. John’s wort INTERACTIONS Increased level: CYP3A4 inhibitors (aldesleukin IL-2, amiodarone, aprepitant, atazanavir, basiliximab, boceprevir, bro- mocriptine, chloramphenicol, clarithro- mycin, conivaptan, danazol, dalfopristin, darunavir, dasatinib, delavirdine, diltiazem, dronedarone, efavirenz, erythromycin, ethinyl estradiol, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, fosaprepitant, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lanreotide, lapatinib, mi- conazole, nefazodone, nelfi navir, nicar- dipine, octreotide, posaconazole, quinine, ranolazine, rifaximin, tamoxifen, telaprevir, telithromycin, tipranavir, troleandomycin, verapamil, voriconazole, zafirlukast) Increased: metformin Increased: dofetilide, coadministration is contraindicated Decrease: dolutegravir-carbamazepine, rifAMPin, an additional dolutegravir 50-mg dose should be taken Decrease: dolutegravir-oxcarbazepine, phenytoin, phenobarbital; avoid coad- ministration Drug/Lab Test Increased: AST/ALT, amylase, bilirubin, CK, glucose, lipase Decrease: neutrophils
Source pages 412, 413, 414
Black Box Warning: Hepatitis B exacer- bation, hepatotoxicity Black Box Warning: Hepatotoxicity/ lactic acidosis: Monitor hepatitis B se- rology, LFTs, plasma hepatitis C RNA, lac- tic acidosis levels. If lab reports confirm these conditions, discontinue product. More common in females or those who are overweight. Avoid use in alcoholism • Patients coinfected with HBV and HIV who discontinue this product should have trans- aminase concentrations monitored q6wk for the first 3 mo and q3-6 mo thereafter. • Resumption of anti–hepatitis B treat- ment may be required. For patients who refuse a fully suppressive antiretroviral regimen but still require treatment for HBV, consider 48 wk of peginterferon alfa; do not administer HIV-active medications in the absence • Periodically monitor serum bilirubin (total and direct), serum creatinine, uri- nalysis, LFTs, amylase, lipase • Pregnancy: obtain pregnancy testing prior to use; hepatitis B exacerbation: those with coexisting HBV and HIV infec- tions who discontinue this product may experience severe acute hepatitis B ex- acerbation with some cases resulting in hepatic decompensation and hepatic failure Evaluate • Therapeutic response: Improvement in CD4, HIV RNC counts, decreasing signs and symptoms of HIV Teach patient/family • That hepatitis and HIV coinfected pa- tients should avoid consuming alcohol; offer vaccinations against hepatitis A/ hepatitis B as appropriate • That GI complaints resolve after 2-3 wk of treatment • To report suspected or planned preg- nancy, not to breastfeed. Instruct moth- ers with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk, inform patients that there is an antiretroviral pregnancy regis- try to monitor fetal outcomes • To take at the same time of day to maintain blood level; not to crush, break, or chew • That product controls the symptoms of HIV but does not cure, that patient is still able to infect others, that other products may be necessary to prevent other infections • Lactic acidosis: to notify prescriber of fatigue, muscle aches/pains, abdominal pain, difficulty breathing, nausea, vomit- ing, change in heart rhythm Black Box Warning: Hepatotoxicity: To notify prescriber of dark urine, yel- lowing skin or eyes, clay-colored stools, anorexia, nausea, vomiting • Discuss with provider all Rx, OTC, herbs and supplements taken, as there are many drug interactions • Immune reconstitution syndrome: advise patients to inform their health care provider immediately of any signs and symptoms of infection, as inflammation from previous infection may occur • Instruct patients that if they miss a dose, to take it as soon as they remem- ber, not to double their next dose or take more than the prescribed dose
Source pages 413, 414
Extracted information for dolutegravir only.
DOSAGE AND ROUTES • Adult and child ≥12 yr and ≥40 kg (treatment naïve or treatment experi- enced but integrase strand transfer in- hibitor naïve): PO 50 mg daily; if given with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifAMPin, give 50 mg bid Infant/child 3 to <14 kg: PO solu- ble tablets for oral suspension (Tivicay PD): 3-<6 kg: 5 mg daily; 6-<10 kg: 15 mg daily; 10-<14 kg: 20 mg daily Infant/child/adolescent >−14 kg: PO soluble tablets for oral suspension (Tivicay PD): 14-<20 kg: 25 mg daily; ≥20 kg: 30 mg daily; tablets (Tivicay): 14-<20 kg: 40 mg daily; ≥20 kg: 50 mg daily INSTI-experienced with any INSTI- associated resistance mutation or clinically suspected INSTI resistance Children and adolescents weighing ≥40 kg: PO tablets (Tivicay): 50 mg bid DOSAGE AND ROUTES Adults: PO One tablet (50 mg dolutegra- vir; 300 mg lamivudine) daily
Source pages 411, 412, 413
Available forms: Tablets 10, 25, 50 mg; dispersible tab 5 mg Available forms: Tablet 50 mg-300 mg
Source pages 412, 413
Administer: • May give without regard to meals, with 8 oz of water • Store at room temperature • Give 2 hr prior to or 6 hr after cation- containing antacids or laxatives, sucral- fate, oral iron, oral calcium, or buffered products Administer: • Give without regard to food • During coadministration with carBA Mazepine or rifAMPin, the dolutegravir dose needs to be increased to 50 mg bid; add 50 mg/day of dolutegravir (sepa- rated by 12 hr from dolutegravir; lamivu- dine) should be given • Avoid use in treatment-experienced patients and in patients with known sub- stitutions associated with resistance to dolutegravir or lamivudine • Do not use within 2 hr prior to or 6 hr after iron or calcium supplement • Do not use within 2 hr prior to or 6 hr after antacids, laxatives, or other medi- cines that contain aluminum, magne- sium, sucralfate, or buffered medicines • Admixtures are stable for ≥24 hr at room temperature
Source pages 412, 413
Extracted information for dolutegravir only.
Assess: • HIV infection: CD4, T-cell count, plasma HIV RNA, viral load; resistance testing prior to treatment, at treatment failure • Drug resistance testing prior to use in treatment-naïve patients • Immune reconstitution syndrome, usually during initial phase of treatment; may need antiinfective prior to starting • Infection: monitor for opportunistic or other infection • Monitor total HDL/LDL cholesterol base- line and periodically; all may be elevated • Pregnancy/breastfeeding: all HIV- positive women should receive antiret- roviral therapy, report pregnancy to the Antiretroviral Pregnancy Registry (800-258-4263); avoid breastfeeding, excretion unknown; glucose screening should be performed at 24-48 wk gesta- tion, confirm gestation age in each tri- mester by ultrasound Assess: • HIV infection: Assess symptoms of HIV, including opportunistic infections, prior to and during treatment, some may be life threatening; monitor plasma CD4+, CD8 cell counts, serum beta-2 micro- globulin, serum antigen levels, treatment failures occur more often in those with baseline HIV-1 RNA concentrations <100,000 copies/mL than in those <100,000 copies/mL; monitor blood glucose, CBC with differential, serum cholesterol, lipid panel
Source pages 412, 414
Evaluate: • Therapeutic response: improvement in cell counts, T-cell counts
Source page 412
CLINICAL CONSIDERATIONS CLINICAL CONSIDERATIONS
Source pages 412, 414
Patient and caregiver information: • To take as prescribed; if dose is missed, to take as soon as remembered up to 1 hr prior to next dose; not to double dose; not to share with others • That sexual partners need to be told that patient has HIV; that product does not cure infection, just controls symptoms, does not prevent infecting others • To report sore throat, fever, fatigue (may indicate infection) • That continued follow-up and lab work will be needed • That fat accumulation/redistribution may occur • To notify prescriber if pregnancy is planned or suspected; to avoid breast- feeding and to continue follow-up exams and lab work (doe-loo-teg′ra-vir/la-mi′vyoo- deen) Dovato
Source page 412
Extracted information for dolutegravir only.
PHARMACOKINETICS Peak 2-3 hr, steady state 5 days, half-life 14 hr, 98% protein binding, metabolized in the liver, excreted in feces 53%, urine 31% PHARMACOKINETICS • Lamivudine: 36% protein binding, half-life is 13 to 19 hr • Dolutegravir: 99% protein binding, metabolism occurs via UDP-glucuronos- yltransferase (UGT)1A1 (major) and by the hepatic isoenzyme CYP3A (minor), half-life 14 hr, 53% excreted unchanged in the feces, urine excretion 31%
Source pages 412, 413
Filter the extracted dose blocks for this individual drug.
• Adult and child ≥12 yr and ≥40 kg (treatment naïve or treatment experi- enced but integrase strand transfer in- hibitor naïve): PO 50 mg daily; if given with efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifAMPin, give 50 mg bid Infant/child 3 to <14 kg: PO solu- ble tablets for oral suspension (Tivicay PD): 3-<6 kg: 5 mg daily; 6-<10 kg: 15 mg daily; 10-<14 kg: 20 mg daily Infant/child/adolescent >−14 kg: PO soluble tablets for oral suspension (Tivicay PD): 14-<20 kg: 25 mg daily; ≥20 kg: 30 mg daily; tablets (Tivicay): 14-<20 kg: 40 mg daily; ≥20 kg: 50 mg daily INSTI-experienced with any INSTI- associated resistance mutation or clinically suspected INSTI resistance Children and adolescents weighing ≥40 kg: PO tablets (Tivicay): 50 mg bid DOSAGE AND ROUTES Adults: PO One tablet (50 mg dolutegra- vir; 300 mg lamivudine) daily
Candidate age grouping · source pages 411, 412, 413