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Drug overview for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
Generic name: ABACAVIR SULFATE/DOLUTEGRAVIR SODIUM/LAMIVUDINE (a-BAK-a-vir/DOE-loo-TEG-ra-vir/la-MIV-ue-deen)
Drug class: Abacavir
Therapeutic class: Anti-Infective Agents
Abacavir, an antiretroviral agent, is a human immunodeficiency virus (HIV) Dolutegravir sodium, an antiretroviral agent, is a human immunodeficiency Lamivudine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI) that is active nucleoside reverse transcriptase inhibitor (NRTI). virus (HIV) integrase strand transfer inhibitor (INSTI). against HIV and hepatitis B virus (HBV).
No enhanced Uses information available for this drug.
Generic name: ABACAVIR SULFATE/DOLUTEGRAVIR SODIUM/LAMIVUDINE (a-BAK-a-vir/DOE-loo-TEG-ra-vir/la-MIV-ue-deen)
Drug class: Abacavir
Therapeutic class: Anti-Infective Agents
Abacavir, an antiretroviral agent, is a human immunodeficiency virus (HIV) Dolutegravir sodium, an antiretroviral agent, is a human immunodeficiency Lamivudine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI) that is active nucleoside reverse transcriptase inhibitor (NRTI). virus (HIV) integrase strand transfer inhibitor (INSTI). against HIV and hepatitis B virus (HBV).
No enhanced Uses information available for this drug.
DRUG IMAGES
TRIUMEQ 600-50-300 MG TABLET
The following indications for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine) have been approved by the FDA:
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
The following dosing information is available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
Abacavir is commercially available as abacavir sulfate; dosage is expressed in terms of abacavir.
Dolutegravir conventional tablets and tablets for oral suspension contain dolutegravir sodium; dosage is expressed in terms of dolutegravir.
Dolutegravir tablets and dolutegravir tablets for oral suspension are not bioequivalent and are not interchangeable on a mg-per-mg basis. The relative bioavailability of dolutegravir tablets for oral suspension is approximately 1.6-fold higher than that of dolutegravir conventional tablets.
If a patient is switched from one tablet formulation to the other, adjust the dosage to that recommended for the specific formulation now being used.
Dosage is based on weight. The tablets for oral suspension are labeled for pediatric patients >=4 weeks of age weighing >=3 kg; conventional tablets are labeled for use in pediatric patients >=4 weeks of age weighing >=14 kg.
The usual dosage of lamivudine for the treatment of HIV-1 infection in adults is 150 mg twice daily or 300 mg once daily.
When lamivudine oral solution containing 10 mg/mL is used for the treatment of HIV-1 infection in pediatric patients 3 months of age or older, the recommended dosage is 5 mg/kg twice daily or 10 mg/kg once daily (up to 300 mg maximum daily dosage). Consider HIV-1 viral load and CD4+ cell count/percentage when selecting the dosing interval for patients initiating treatment with oral solution.
When lamivudine 150-mg scored tablets are used in pediatric patients 3 months of age or older who weigh 14 kg or more and are able to swallow tablets, the recommended dosage is based on weight (see Table 1and Table 2). Data regarding efficacy of the once-daily regimen of lamivudine given as 150-mg scored tablets in pediatric patients 3 months of age or older is limited to those who transitioned from a twice-daily regimen to a once-daily regimen after 36 weeks of treatment.
Table 1. Twice-daily Lamivudine for Treatment of HIV-1 Infection in Pediatric Patients Weighing at least 14 kg (150-mg Tablets)
Weight (kg) AM Dose PM Dose 14 to <20 75 mg (half of 150-mg 75 mg (half of 150-mg tablet) tablet) 20 to <25 75 mg (half of 150-mg 150 mg (one 150-mg tablet) tablet) >=25 150 mg (one 150-mg 150 mg (one 150-mg tablet) tablet)
Table 2. Once-daily Lamivudine for Treatment of HIV-1 Infection in Pediatric Patients Weighing at least 14 kg (150-mg Tablets)
Weight (kg) Once-daily Dose 14 to <20 150 mg (one 150-mg tablet) 20 to <25 225 mg (one and one-half 150-mg tablets) >=25 300 mg (two 150-mg tablets or one 300-mg tablet)
Although safety and efficacy of lamivudine in infants younger than 3 months of age have not been established, some experts suggest that neonates younger than 4 weeks of age+ can receive lamivudine in a dosage of 2 mg/kg twice daily and infants 4 weeks of age or older+ can receive a dosage of 4 mg/kg (up to 150 mg) twice daily.
When empiric HIV therapy+ is used for prevention of perinatal HIV transmission + in neonates at highest risk of HIV acquisition, a 3-drug antiretroviral regimen of zidovudine, lamivudine, and nevirapine is recommended and should be initiated as soon as possible after birth (within 6-12 hours).
For empiric HIV therapy+ in HIV-exposed neonates, experts recommend that lamivudine be given in a dosage of 2 mg/kg twice daily from birth to 4 weeks of age followed by 4 mg/kg twice daily from 4-6 weeks of age.
The optimal duration of empiric HIV therapy+ in HIV-exposed neonates at highest risk of HIV acquisition is unknown. Many experts recommend that the 3-drug regimen be continued for 6 weeks; others discontinue nevirapine and/or lamivudine if the result of the neonate's HIV nucleic acid amplification test (NAAT) is negative, but recommend continuing zidovudine for 6 weeks.
Clinicians can consult the National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for the prevention of perinatal HIV transmission.
When lamivudine (100-mg tablets or oral solution containing 5 mg/mL) is used for the treatment of chronic HBV infection in adults, the recommended dosage is 100 mg once daily.
The recommended oral dosage of lamivudine for the treatment of chronic HBV infection in pediatric patients 2-17 years of age is 3 mg/kg once daily up to a maximum daily dosage of 100 mg. The oral solution formulation should be prescribed for patients requiring a dosage less than 100 mg or unable to swallow tablets.
Dolutegravir conventional tablets and tablets for oral suspension contain dolutegravir sodium; dosage is expressed in terms of dolutegravir.
Dolutegravir tablets and dolutegravir tablets for oral suspension are not bioequivalent and are not interchangeable on a mg-per-mg basis. The relative bioavailability of dolutegravir tablets for oral suspension is approximately 1.6-fold higher than that of dolutegravir conventional tablets.
If a patient is switched from one tablet formulation to the other, adjust the dosage to that recommended for the specific formulation now being used.
Dosage is based on weight. The tablets for oral suspension are labeled for pediatric patients >=4 weeks of age weighing >=3 kg; conventional tablets are labeled for use in pediatric patients >=4 weeks of age weighing >=14 kg.
The usual dosage of lamivudine for the treatment of HIV-1 infection in adults is 150 mg twice daily or 300 mg once daily.
When lamivudine oral solution containing 10 mg/mL is used for the treatment of HIV-1 infection in pediatric patients 3 months of age or older, the recommended dosage is 5 mg/kg twice daily or 10 mg/kg once daily (up to 300 mg maximum daily dosage). Consider HIV-1 viral load and CD4+ cell count/percentage when selecting the dosing interval for patients initiating treatment with oral solution.
When lamivudine 150-mg scored tablets are used in pediatric patients 3 months of age or older who weigh 14 kg or more and are able to swallow tablets, the recommended dosage is based on weight (see Table 1and Table 2). Data regarding efficacy of the once-daily regimen of lamivudine given as 150-mg scored tablets in pediatric patients 3 months of age or older is limited to those who transitioned from a twice-daily regimen to a once-daily regimen after 36 weeks of treatment.
Table 1. Twice-daily Lamivudine for Treatment of HIV-1 Infection in Pediatric Patients Weighing at least 14 kg (150-mg Tablets)
Weight (kg) AM Dose PM Dose 14 to <20 75 mg (half of 150-mg 75 mg (half of 150-mg tablet) tablet) 20 to <25 75 mg (half of 150-mg 150 mg (one 150-mg tablet) tablet) >=25 150 mg (one 150-mg 150 mg (one 150-mg tablet) tablet)
Table 2. Once-daily Lamivudine for Treatment of HIV-1 Infection in Pediatric Patients Weighing at least 14 kg (150-mg Tablets)
Weight (kg) Once-daily Dose 14 to <20 150 mg (one 150-mg tablet) 20 to <25 225 mg (one and one-half 150-mg tablets) >=25 300 mg (two 150-mg tablets or one 300-mg tablet)
Although safety and efficacy of lamivudine in infants younger than 3 months of age have not been established, some experts suggest that neonates younger than 4 weeks of age+ can receive lamivudine in a dosage of 2 mg/kg twice daily and infants 4 weeks of age or older+ can receive a dosage of 4 mg/kg (up to 150 mg) twice daily.
When empiric HIV therapy+ is used for prevention of perinatal HIV transmission + in neonates at highest risk of HIV acquisition, a 3-drug antiretroviral regimen of zidovudine, lamivudine, and nevirapine is recommended and should be initiated as soon as possible after birth (within 6-12 hours).
For empiric HIV therapy+ in HIV-exposed neonates, experts recommend that lamivudine be given in a dosage of 2 mg/kg twice daily from birth to 4 weeks of age followed by 4 mg/kg twice daily from 4-6 weeks of age.
The optimal duration of empiric HIV therapy+ in HIV-exposed neonates at highest risk of HIV acquisition is unknown. Many experts recommend that the 3-drug regimen be continued for 6 weeks; others discontinue nevirapine and/or lamivudine if the result of the neonate's HIV nucleic acid amplification test (NAAT) is negative, but recommend continuing zidovudine for 6 weeks.
Clinicians can consult the National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for the prevention of perinatal HIV transmission.
When lamivudine (100-mg tablets or oral solution containing 5 mg/mL) is used for the treatment of chronic HBV infection in adults, the recommended dosage is 100 mg once daily.
The recommended oral dosage of lamivudine for the treatment of chronic HBV infection in pediatric patients 2-17 years of age is 3 mg/kg once daily up to a maximum daily dosage of 100 mg. The oral solution formulation should be prescribed for patients requiring a dosage less than 100 mg or unable to swallow tablets.
Abacavir sulfate is administered orally once or twice daily without regard to meals. If a dose of abacavir is missed, administer the dose as soon as possible. Do not double the next dose or take more than the prescribed dose.
Abacavir is commercially available as a single entity preparation and in the following fixed-combination tablets for oral use: abacavir and lamivudine (Epzicom(R)); abacavir, lamivudine, and zidovudine (Trizivir(R)); and abacavir, dolutegravir, and lamivudine (Triumeq(R) and Triumeq PD(R)). Since the antiretroviral agents contained in the fixed combination preparations also may be available in single-entity or other fixed-combination preparations, exercise care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals. Single-entity abacavir sulfate is commercially available as an oral solution or tablets.
Abacavir oral solution is used in pediatric patients or when a solid oral dosage form is inappropriate. The scored 300-mg abacavir tablets are used in adults and may be used in children weighing 14 kg or greater who have undergone assessment demonstrating ability to reliably swallow tablets. Store abacavir tablets and oral solution between 20-25degreesC.
The oral solution may also be refrigerated. Single-entity dolutegravir is commercially available as conventional tablets (Tivicay(R)) and as tablets for oral suspension (Tivicay(R) PD). The single-entity tablets and tablets for oral suspension must be used in conjunction with other antiretrovirals.
Administer dolutegravir sodium orally once or twice daily without regard to food. Do not chew, cut, or crush the tablets for oral suspension. Dolutegravir tablets for oral suspension may be either swallowed whole (1 tablet at time if more than a single tablet is required for the dose, to reduce the risk of choking), or dispersed in drinking water to provide an oral suspension.
To prepare an oral suspension, add the indicated number of 5-mg tablets for oral suspension to the appropriate volume of clean drinking water in the plastic cup provided by the manufacturer. To prepare a 5- or 15-mg dose of dolutegravir, place 5 mL of drinking water into the cup and add 1 or 3 tablets for oral suspension, respectively, to the water. To prepare a 20-, 25-, or 30-mg dose, place 10 mL of drinking water into the cup and add 4, 5, or 6 tablets for oral suspension, respectively, to the water.
Gently swirl the cup for 1-2 minutes until there are no remaining lumps. After full dispersion, administer the oral suspension within 30 minutes of mixing For infants who cannot drink from the plastic cup, administer the oral suspension using the oral syringe provided by the manufacturer. To ensure that the child receives the full dose, place an additional 5 mL of drinking water into the cup, swirl the cup, and administer to the child directly from the cup or using the oral syringe.
For more specific instructions on preparation and administration of dolutegravir oral suspension, consult the manufacturer's instructions for use and labeling. Store the conventional tablets at controlled room temperature of 25degreesC (excursions permitted to 15-30oC). Store the tablets for oral suspension below 30degreesC.
Store and dispense in the original bottle, protect from moisture, and keep the bottle tightly closed; do not remove the desiccant. Lamivudine is administered orally once or twice daily without regard to meals. For the treatment of HIV-1 infection, lamivudine is commercially available as an oral solution containing 10 mg/mL or tablets containing 150 or 300 mg of the drug (Epivir(R), generic).
The 150-mg scored tablets are the preferred preparation in pediatric patients who weigh 14 kg or more and can swallow tablets. The oral solution should be used in those unable to safely and reliably swallow tablets. Lamivudine is used in conjunction with other antiretrovirals for the treatment of HIV-1 infection.
For the treatment of chronic HBV infection, lamivudine is commercially available as an oral solution containing 5 mg/mL or film-coated tablets containing 100 mg of the drug (Epivir-HBV(R), generic). The 5-mg/mL oral solution should be used in patients requiring a dosage less than 100 mg and in children unable to reliably swallow tablets. Lamivudine preparations labeled by FDA for treatment of chronic HBV infection should not be used in HIV-infected patients because they contain a lower dosage of the drug than that required for treatment of HIV-1 infection.
If such preparations are used for the management of chronic HBV infection in a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy for HIV-infected individuals. Store lamivudine 100-mg, 150-mg, and 300-mg tablets at 25degreesC (excursions permitted between 15-30degreesC). Store lamivudine 5-mg/mL oral solution at 20-25degreesC and store lamivudine 10-mg/mL oral solution at 25degreesC.
Abacavir is commercially available as a single entity preparation and in the following fixed-combination tablets for oral use: abacavir and lamivudine (Epzicom(R)); abacavir, lamivudine, and zidovudine (Trizivir(R)); and abacavir, dolutegravir, and lamivudine (Triumeq(R) and Triumeq PD(R)). Since the antiretroviral agents contained in the fixed combination preparations also may be available in single-entity or other fixed-combination preparations, exercise care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals. Single-entity abacavir sulfate is commercially available as an oral solution or tablets.
Abacavir oral solution is used in pediatric patients or when a solid oral dosage form is inappropriate. The scored 300-mg abacavir tablets are used in adults and may be used in children weighing 14 kg or greater who have undergone assessment demonstrating ability to reliably swallow tablets. Store abacavir tablets and oral solution between 20-25degreesC.
The oral solution may also be refrigerated. Single-entity dolutegravir is commercially available as conventional tablets (Tivicay(R)) and as tablets for oral suspension (Tivicay(R) PD). The single-entity tablets and tablets for oral suspension must be used in conjunction with other antiretrovirals.
Administer dolutegravir sodium orally once or twice daily without regard to food. Do not chew, cut, or crush the tablets for oral suspension. Dolutegravir tablets for oral suspension may be either swallowed whole (1 tablet at time if more than a single tablet is required for the dose, to reduce the risk of choking), or dispersed in drinking water to provide an oral suspension.
To prepare an oral suspension, add the indicated number of 5-mg tablets for oral suspension to the appropriate volume of clean drinking water in the plastic cup provided by the manufacturer. To prepare a 5- or 15-mg dose of dolutegravir, place 5 mL of drinking water into the cup and add 1 or 3 tablets for oral suspension, respectively, to the water. To prepare a 20-, 25-, or 30-mg dose, place 10 mL of drinking water into the cup and add 4, 5, or 6 tablets for oral suspension, respectively, to the water.
Gently swirl the cup for 1-2 minutes until there are no remaining lumps. After full dispersion, administer the oral suspension within 30 minutes of mixing For infants who cannot drink from the plastic cup, administer the oral suspension using the oral syringe provided by the manufacturer. To ensure that the child receives the full dose, place an additional 5 mL of drinking water into the cup, swirl the cup, and administer to the child directly from the cup or using the oral syringe.
For more specific instructions on preparation and administration of dolutegravir oral suspension, consult the manufacturer's instructions for use and labeling. Store the conventional tablets at controlled room temperature of 25degreesC (excursions permitted to 15-30oC). Store the tablets for oral suspension below 30degreesC.
Store and dispense in the original bottle, protect from moisture, and keep the bottle tightly closed; do not remove the desiccant. Lamivudine is administered orally once or twice daily without regard to meals. For the treatment of HIV-1 infection, lamivudine is commercially available as an oral solution containing 10 mg/mL or tablets containing 150 or 300 mg of the drug (Epivir(R), generic).
The 150-mg scored tablets are the preferred preparation in pediatric patients who weigh 14 kg or more and can swallow tablets. The oral solution should be used in those unable to safely and reliably swallow tablets. Lamivudine is used in conjunction with other antiretrovirals for the treatment of HIV-1 infection.
For the treatment of chronic HBV infection, lamivudine is commercially available as an oral solution containing 5 mg/mL or film-coated tablets containing 100 mg of the drug (Epivir-HBV(R), generic). The 5-mg/mL oral solution should be used in patients requiring a dosage less than 100 mg and in children unable to reliably swallow tablets. Lamivudine preparations labeled by FDA for treatment of chronic HBV infection should not be used in HIV-infected patients because they contain a lower dosage of the drug than that required for treatment of HIV-1 infection.
If such preparations are used for the management of chronic HBV infection in a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy for HIV-infected individuals. Store lamivudine 100-mg, 150-mg, and 300-mg tablets at 25degreesC (excursions permitted between 15-30degreesC). Store lamivudine 5-mg/mL oral solution at 20-25degreesC and store lamivudine 10-mg/mL oral solution at 25degreesC.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| TRIUMEQ 600-50-300 MG TABLET | Maintenance | Adults take 1 tablet by oral route once daily |
No generic dosing information available.
The following drug interaction information is available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Dofetilide/Dolutegravir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Dolutegravir may inhibit the elimination of dofetilide by the renal organic cation transporter (OCT2).(1) CLINICAL EFFECTS: Concurrent use of dolutegravir may result in elevated levels of dofetilide.(1) Dofetilide has been shown to prolong the QTc interval in a dose-dependent fashion. Concurrent use with other agents that prolong the QTc interval may result in additive effects on the QTc interval which may result in potentially life-threatening cardiac arrhythmias, including torsades de pointes(TdP).(2) PREDISPOSING FACTORS: Renal impairment may increase risk for excessive QTc prolongation as dofetilide is primarily renally eliminated. To prevent increased serum levels and risk for ventricular arrhythmias, dofetilide must be dose adjusted for creatinine clearance < or = to 60 mL/min.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(3) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(3) PATIENT MANAGEMENT: Concurrent use of dofetilide and dolutegravir is contraindicated. If dofetilide is to be discontinued, a washout of at least 2 days is recommended prior to starting dolutegravir.(1,2) If concurrent therapy is deemed medically necessary, obtain serum calcium, magnesium, and potassium levels and monitor ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: Dolutegravir has been shown to inhibit OCT2 in vitro and in vivo and is expected to inhibit the excretion of dofetilide.(1) |
DOFETILIDE, TIKOSYN |
There are 10 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Dolutegravir/Etravirine; Efavirenz; Nevirapine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etravirine, efavirenz, and nevirapine may induce the metabolism of dolutegravir via CYP3A4.(1,2) Efavirenz may also induce dolutegravir metabolism via UGT enzymes. CLINICAL EFFECTS: Concurrent use of etravirine, efavirenz, or nevirapine and dolutegravir may result in decreased levels of and clinical effectiveness of dolutegravir.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of dolutegravir states that dolutegravir should not be used with etravirine without atazanavir/ritonavir (ATVr), darunavir/ritonavir (DRVr), or lopinavir/ritonavir (LPVr).(1) The Canadian(3) and UK(4) manufacturers of dolutegravir state that INSTI-naive patients may use etravirine concurrently with dolutegravir at an increased dose of 50 mg twice daily. In pediatric patients, the weight-based once daily dose should be given twice daily. No dose adjustment for dolutegravir is needed when used with etravirine along with concurrent ATVr, DRVr, or LPVr.(1,3-5) When used with efavirenz, the dosage of dolutegravir should be 50 mg twice daily.(1,2) When using the combination abacavir-dolutegravir-lamivudine product, an additional 50 mg dolutegravir table should be taken 12 hours apart from the combination product.(2) Alternative combinations that do not induce metabolic inducers should be considered when possible for INSTI-experience patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance. In pediatric patients, increase the weight-based dose to twice daily. Refer to the current labeling for the specific dosing recommendation.(1) Although the US(1) and Canadian(3) manufacturers of dolutegravir recommend avoiding concurrent use of nevirapine, the US Department of Health and Human Services HIV guidelines recommend standard doses of dolutegravir when administered concurrently with nevirapine.(5) The UK manufacturer of dolutegravir recommends increasing the dose of dolutegravir to 50 mg twice daily when used concurrently with nevirapine.(4) DISCUSSION: In a study in 12 subjects, the administration of efavirenz with dolutegravir (50 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 39%, 57%, and 75%, respectively.(1) In a study in 16 subjects, the administration of etravirine with dolutegravir (50 mg daily) decreased the Cmax, AUC, and Cmin of dolutegravir by 52%, 71%, and 88%, respectively.(1) In a study in 9 subjects, the administration of etravirine and darunavir/ritonavir (200 mg and 600/100 mg BID) with dolutegravir (50 mg daily) decreased the Cmax, AUC, and Cmin of dolutegravir by 12%, 25%, and 37%, respectively.(1) In a study in 8 subjects, the administration of efavirenz and lopinavir/ritonavir (200 mg and 400/100 mg BID) with dolutegravir (50 mg daily) increased the Cmax, AUC, and Cmin of dolutegravir by 7%, 11%, and 28%, respectively.(1) |
EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, ETRAVIRINE, INTELENCE, NEVIRAPINE, NEVIRAPINE ER, SYMFI |
| Dolutegravir/Selected UGT1A & CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Dolutegravir is metabolized by UGT1A1 and to a smaller extent by CYP3A4. Inducers of UGT1A1 and CYP3A4 may induce the metabolism of dolutegravir.(1-6) CLINICAL EFFECTS: Concurrent use of UGT1A1 and CYP3A4 inducers may result in decreased levels of and clinical effectiveness of dolutegravir.(1-6) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: When used with carbamazepine, fosamprenavir/ritonavir, rifampin, or tipranavir/ritonavir, the dosage of dolutegravir should be 50 mg twice daily. When using the combination abacavir-dolutegravir-lamivudine or dolutegravir-lamivudine product, an additional 50 mg dolutegravir table should be taken 12 hours apart from the combination product. In pediatric patients, increase the weight-based dose to twice daily. Refer to the current labeling for the specific dosing recommendation. Alternative combinations that do not induce metabolic inducers should be considered when possible for INSTI-experience patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.(1,4-6) Recommendations for other UGT1A1 and CYP3A4 inducers differ by region. The US manufacturer of dolutegravir states that concurrent use should be avoided due to insufficient data to make dosing recommendations for concomitant use.(1,4) The Canadian and UK manufacturers of dolutegravir state that the dosage of dolutegravir should be 50 mg twice daily when used concurrently with other UGT1A1 and CYP3A4 inducers. When using the combination abacavir-dolutegravir-lamivudine product, an additional 50 mg dolutegravir table should be taken 12 hours apart from the combination product. In pediatric patients, increase the weight-based dose to twice daily. Refer to the current labeling for the specific dosing recommendation. Alternative combinations that do not induce metabolic inducers should be considered when possible for patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.(5,6) DISCUSSION: In a study in 12 subjects, the administration of fosamprenavir/ritonavir (700/100 mg BID) with dolutegravir (50 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 24%, 35%, and 49%, respectively.(1) In a study in 11 subjects, the administration of rifampin (600 mg daily) with dolutegravir (50 mg BID) decreased the Cmax, AUC, and Cmin of dolutegravir by 43%, 54%, and 32%, respectively, when compared to the administration of dolutegravir (50 mg BID) alone.(1) In a study in 11 subjects, the administration of rifampin (600 mg daily) with dolutegravir (50 mg BID) increased the Cmax, AUC, and Cmin of dolutegravir by 18%, 33%, and 22%, respectively, when compared to the administration of dolutegravir (50 mg daily) alone.(1) In a study in 14 subjects, the administration of tipranavir/ritonavir (500/200 mg BID) with dolutegravir (50 mg daily) decreased the Cmax, AUC, and Cmin of dolutegravir by 46%, 59%, and 76%, respectively.(1) In a study in 16 subjects, the administration of carbamazepine (300 mg twice daily) with dolutegravir (50 mg daily) decreased the Cmax, AUC, and Cmin of dolutegravir by 33%, 49%, and 73%, respectively. (1) UGT1A1 and CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosamprenavir/ritonavir, fosphenytoin, ivosidenib, lorlatinib, lumacaftor, mitotane, oxcarbazepine, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and tipranavir/ritonavir.(1,7) |
APTIVUS, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSAMPRENAVIR CALCIUM, FOSPHENYTOIN SODIUM, LORBRENA, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, OXCARBAZEPINE, OXCARBAZEPINE ER, OXTELLAR XR, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFADIN, RIFAMPIN, SEZABY, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, TRILEPTAL, XTANDI |
| Deoxycytidine Kinase Substrates/Cladribine (Oral) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of cladribine by deoxycytidine kinase (dCK). CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine, or zalcitabine with cladribine may result in decreased clinical efficacy of cladribine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and cladribine is not recommended.(1) The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation should be avoided.(2) DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites. In a case report, a patient on lamivudine who received cladribine concurrently did not experience a decrease in his lymphocyte count. After discontinuation of lamivudine and readministration of cladribine, his lymphocytes dropped as expected.(3) It is expected that other compounds phosphorylated by dCK would also decrease cladribine's efficacy.(4) Compounds phosphorylated by dCK include: clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine. |
MAVENCLAD |
| Dalfampridine/Cimetidine; Dolutegravir SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cimetidine and dolutegravir inhibit the organic cation transporter 2 (OCT2). Dalfampridine is eliminated mainly via the kidneys with active renal secretion by OCT2.(1-3) CLINICAL EFFECTS: The concurrent administration of dalfampridine with an inhibitor of OCT2 may result in elevated levels of dalfampridine and signs of toxicity. Elevated levels of dalfampridine may increase the risk of seizures.(1,2) PREDISPOSING FACTORS: Renal impairment. PATIENT MANAGEMENT: The US manufacturer of dalfampridine states that the potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures. If concurrent use is warranted, carefully monitor patients for adverse effects. Permanently discontinue dalfampridine in patients who have a seizure while on treatment.(1) The UK and Canadian manufacturers of dalfampridine states that concurrent use of dalfampridine and OCT2 inhibitors is contraindicated.(4,5) DISCUSSION: In a single dose clinical study in 23 healthy volunteers, the combined use of cimetidine (400 mg every 6 hours) increased the area-under-curve (AUC) of cimetidine approximately 25% due to a reduction in the clearance of dalfampridine.(1) |
4-AMINOPYRIDINE, AMPYRA, DALFAMPRIDINE, DALFAMPRIDINE ER |
| Sorbitol/Lamivudine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sorbitol increases the osmotic pressure in the intestine, resulting in accelerated small intestinal transit time and decreased absorption and bioavailability of lamivudine. CLINICAL EFFECTS: Concurrent administration of sorbitol and lamivudine may result in decreased clinical efficacy of lamivudine.(1) Reduction in lamivudine exposure is sorbitol dose-dependent. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and sorbitol should be avoided.(1) Consider more frequent monitoring of HBV viral load when chronic coadministration cannot be avoided. DISCUSSION: In an open label, randomized sequence, 4-period, crossover trial in 16 healthy adults, coadministration of a single dose of lamivudine (300 mg) with sorbitol (3.2 grams) resulted in a dose-dependent decrease of lamivudine's area-under-the-curve (AUC(0-24), AUC infinity) and maximum concentration (Cmax) of 20%, 28%, and 28%. A single dose of lamivudine with sorbitol (10.2 grams) resulted in a decrease of lamivudine's AUC and Cmax of 39%, 52%, and 52%. A single dose of lamivudine with sorbitol (13.4 grams) resulted in a decrease of lamivudine's AUC and Cmax of 36%, 55%, and 55%.(1) |
KIONEX, SPS |
| Riociguat/Abacavir SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Riociguat is primarily metabolized by CYP1A1 and to a lesser extent by CYP3A4/3A5 and CYP2J2.(1,2) Abacavir has been shown to inhibit CYP1A1 in vitro and may decrease the metabolism of riociguat.(2,3) CLINICAL EFFECTS: Concurrent use of abacavir with riociguat may result in elevated systemic levels and toxicity (e.g. hypotension) from riociguat.(2,3) PREDISPOSING FACTORS: The risk for riociguat-associated hypotension is higher in patients with a systolic blood pressure (SBP) < or = 110 prior to treatment initiation or dose increase. Patient specific factors such as renal or hepatic impairment, or age > 65 years are associated with higher systemic exposure to riociguat and may increase interaction risk or severity.(1,4) PATIENT MANAGEMENT: The US manufacturer of abacavir states that the dose of riociguat may need to be reduced when used concurrently.(3) Although the manufacturer of riociguat does not make any recommendations for dose adjustment when used with a CYP1A1 inhibitor, it has been suggested that the initial dose of riociguat be reduced to 0.5 mg 3 times daily. This is the same dose modification recommended during concurrent therapy with strong CYP and P-gp/BCRP inhibitors, based on a similar magnitude of interaction between riociguat and ketoconazole.(2) Monitor blood pressure and counsel patient to report low blood pressure, lightheadedness or chest pain. Patients stabilized on concomitant therapy may need to have their riociguat dose retitrated upward after discontinuation of abacavir. DISCUSSION: In an interaction study of 8 HIV-positive patients without pulmonary hypertension, abacavir (given as a fixed-dose combination of abacavir 600 mg-dolutegravir 50 mg-lamivudine 300 mg once daily) increased the area-under-curve (AUC) of single-dose riociguat 0.5 mg by about 3-fold, compared to historical healthy volunteers administered single-dose riociguat 0.5 mg alone.(2) The frequency or magnitude of this interaction is difficult to predict in a specific patient due to significant interpatient variability in drug kinetics. For example, between patient variability in systemic exposure (AUC) relative to dose is 90%. The amount of riociguat metabolized may be as low as 27% or as high as 72%. Cigarette smoking induces the CYP1A1 mediated metabolism of riociguat leading to about a 50% decrease in systemic exposure compared with non-smoking patients. |
ADEMPAS |
| Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1) |
ZYNTEGLO |
| Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1) |
SKYSONA |
| Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1) |
LYFGENIA |
| Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1) |
LENMELDY |
There are 7 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Dolutegravir/Selected Oral Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, sucralfate, and zinc may form chelation compounds with dolutegravir.(1) CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate close to the administration time of dolutegravir may result in decreased absorption and clinical effectiveness of dolutegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy with dolutegravir and cation-containing products. If it is necessary to use these agents concurrently, dolutegravir should be administered 2 hours before or 6 hours after taking these medications.(1) Alternatively, dolutegravir and supplements containing calcium or iron can be taken together with food.(1) DISCUSSION: In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) simultaneously with dolutegravir (50 mg single dose) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 72%, 74%, and 74%, respectively.(1) In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) 2 hours after dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 18%, 26%, and 30%, respectively.(1) In a study in 16 subjects, the administration of a multiple vitamin (One-A-Day) simultaneously with dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 35%, 33%, and 32%, respectively.(1) |
ACCRUFER, ALUMINUM HYDROXIDE, AUROVELA 24 FE, AUROVELA FE, AURYXIA, AVERI, BALCOLTRA, BLISOVI 24 FE, BLISOVI FE, CALCIUM ACETATE, CALCIUM CHLORIDE, CALCIUM GLUCONATE, CALCIUM GLUCONATE MONOHYDRATE, CARAFATE, CHARLOTTE 24 FE, CLENPIQ, FEIRZA, FERRIC CITRATE, FINZALA, FOSRENOL, GALBRIELA, GALZIN, GEMMILY, HAILEY 24 FE, HAILEY FE, JOYEAUX, JUNEL FE, JUNEL FE 24, KAITLIB FE, KAOLIN, LANTHANUM CARBONATE, LARIN 24 FE, LARIN FE, LEVONORG-ETH ESTRAD-FE BISGLYC, LO LOESTRIN FE, LOESTRIN FE, MAGNESIUM CHLORIDE, MAGNESIUM CITRATE, MAGNESIUM OXIDE, MAGNESIUM SULFATE, MERZEE, MIBELAS 24 FE, MICROGESTIN FE, MINZOYA, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRONE-E.ESTRADIOL-IRON, SOD SULF-POTASS SULF-MAG SULF, SUCRALFATE, SUFLAVE, SUPREP, SUTAB, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-LEGEST FE, VELPHORO, WILZIN, WYMZYA FE, XARAH FE, XELRIA FE, ZINC ACETATE, ZINC CHLORIDE, ZINC OXIDE, ZINC SULFATE, ZINC UNDECYLENATE |
| Metformin/Dolutegravir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Dolutegravir may inhibit the renal organic cation transporter, OCT2, responsible for the elimination of metformin.(1) CLINICAL EFFECTS: Concurrent use may result in increased plasma levels of metformin and toxicity such as lactic acidosis. Untreated lactic acidosis may be fatal. Symptoms of lactic acidosis include malaise, myalgias, respiratory distress, low pH, increased anion gap and elevated blood lactate. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: With concomitant use, assess the benefit and risk of metformin in patients on dolutegravir. When starting or stopping dolutegravir, the metformin dose may require an adjustment. Monitor blood glucose when initiating concomitant use and after stopping dolutegravir.(1) Monitor patient's renal function and for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: low pH, an increased anion gap, and increased lactate to pyruvate ratio.(1) DISCUSSION: Dolutegravir has been shown to inhibit OCT2 in vitro and in vivo and is expected to inhibit the excretion of metformin.(1) In a study in 15 subjects, concomitant metformin (500 mg twice daily) with dolutegravir (50 mg daily) increased the concentration maximum (Cmax) and area-under-curve (AUC) of metformin by 66% and 79%, respectively. In a study in 15 subjects, concomitant metformin (500 mg twice daily) with dolutegravir (50 mg twice daily) increased the Cmax and AUC of metformin by 111% and 145%, respectively.(1) |
ACTOPLUS MET, ALOGLIPTIN-METFORMIN, DAPAGLIFLOZIN-METFORMIN ER, GLIPIZIDE-METFORMIN, GLYBURIDE-METFORMIN HCL, INVOKAMET, INVOKAMET XR, JANUMET, JANUMET XR, JENTADUETO, JENTADUETO XR, KAZANO, METFORMIN ER GASTRIC, METFORMIN ER OSMOTIC, METFORMIN HCL, METFORMIN HCL ER, PIOGLITAZONE-METFORMIN, RIOMET, SAXAGLIPTIN-METFORMIN ER, SEGLUROMET, SITAGLIPTIN-METFORMIN, SITAGLIPTIN-METFORMIN ER, SYNJARDY, SYNJARDY XR, TRIJARDY XR, XIGDUO XR, ZITUVIMET, ZITUVIMET XR |
| Cisplatin/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of cisplatin by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicities from cisplatin, including nephrotoxicity, ototoxicity, neuropathy, and myelosuppression.(1,2) PREDISPOSING FACTORS: Pre-existing renal insufficiency, advanced age, and dehydration may increase the risk of nephrotoxicity. PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of cisplatin with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor closely for toxicities of cisplatin and consider dosage reduction of cisplatin.(1,2) DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(2) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, dolutegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(3) |
CISPLATIN, KEMOPLAT |
| Clofarabine/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of clofarabine by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicity from clofarabine, including myelosuppression, serious hemorrhages, enterocolitis, nephrotoxicity, and hepatotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of clofarabine with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of the clofarabine and consider dosage reduction of clofarabine.(1) DISCUSSION: In an animal study, cimetidine, an OCT2 inhibitor, decreased the clearance of clofarabine in rats by 61%. The clinical implications of this finding are unclear.(1,2) In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(3) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(4) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, cimetidine, dolutegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(5) |
CLOFARABINE |
| Procainamide/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of procainamide by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicities of procainamide,(1,2) including potentially life-threatening cardiac arrhythmias, like torsades de pointes (TdP).(3) PREDISPOSING FACTORS: Risk factors for QT prolongation include: cardiovascular disease (e.g. heart failure, recent myocardial infarction, history of torsades de pointes, congenital long QT syndrome), female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, advanced age, and concurrent use of agents known to cause QT prolongation.(3) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(3) PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of procainamide with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of procainamide and consider dosage reduction of procainamide.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(2) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, cimetidine, dolutegravir, givinostat, isavuconazole, trilaciclib, tucatinib, and vimseltinib.(4) |
PROCAINAMIDE HCL |
| Oxaliplatin/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of oxaliplatin by OCT2 in the kidneys.(1) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicity from oxaliplatin, including myelosuppression and potentially life-threatening cardiac arrhythmias, including torsades de pointes (TdP).(1) PREDISPOSING FACTORS: Risk factors for QT prolongation include: cardiovascular disease (e.g. heart failure, recent myocardial infarction, history of torsades de pointes, congenital long QT syndrome), female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, advanced age, and concurrent use of agents known to cause QT prolongation.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of oxaliplatin with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of oxaliplatin and consider dosage reduction.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(3) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(4) OCT2 inhibitors linked to this monograph include: arimoclomol, dolutegravir, givinostat, trilaciclib, and vimseltinib.(5) |
OXALIPLATIN |
| Pindolol/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of pindolol by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicity from pindolol.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of pindolol with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of pindolol and consider dosage reduction of pindolol.(1,2) DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(2) OCT2 inhibitors linked to this monograph include: arimoclomol, cimetidine, dolutegravir, givinostat, and vimseltinib.(3) |
PINDOLOL |
The following contraindication information is available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
Drug contraindication overview.
*Presence of the human leukocyte antigen (HLA)-B*5701 allele. *Moderate or severe hepatic impairment. *History of hypersensitivity reaction to abacavir.
*Previous hypersensitivity reaction to dolutegravir. *Concomitant use with dofetilide. *Previous hypersensitivity to lamivudine.
*Presence of the human leukocyte antigen (HLA)-B*5701 allele. *Moderate or severe hepatic impairment. *History of hypersensitivity reaction to abacavir.
*Previous hypersensitivity reaction to dolutegravir. *Concomitant use with dofetilide. *Previous hypersensitivity to lamivudine.
There are 6 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Acute pancreatitis |
| Chronic pancreatitis |
| HLa-B *57:01 positive |
| Lactation |
| Lactic acidosis |
| Pancreatitis |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Child-pugh class A hepatic impairment |
| Chronic hepatitis B |
| Chronic hepatitis C |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Disease of liver |
There are 6 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Coronary artery disease |
| Hypertriglyceridemia |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| UGt1a1*28 polymorphism |
The following adverse reaction information is available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
Adverse reaction overview.
Adverse effects of at least moderate intensity reported in 10% or more of In patients receiving dolutegravir in an adult clinical trial, the most adult patients receiving abacavir for HIV-1 infection include nausea, common adverse effects of moderate to severe intensity and incidence >=2% headache, fatigue and malaise, nausea and vomiting, and dreams/sleep were insomnia, headache, and fatigue. disorders. Adverse effects of at least moderate intensity reported in 5% or more of pediatric patients receiving abacavir for HIV-1 infection include fever and/or chills, nausea and vomiting, skin rash, and ear, nose, and throat infections.
In the treatment of HIV infection in adults, the most common reported adverse reactions (incidence >=15%) were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough. In the treatment of HIV infection in pediatric patients, the most common reported adverse reactions (incidence >=15%) were fever and cough. In the treatment of HBV infection, the most common reported adverse reactions (incidence >=10% and reported at a rate greater than placebo) were ear, nose, and throat infections; sore throat; and diarrhea.
Adverse effects of at least moderate intensity reported in 10% or more of In patients receiving dolutegravir in an adult clinical trial, the most adult patients receiving abacavir for HIV-1 infection include nausea, common adverse effects of moderate to severe intensity and incidence >=2% headache, fatigue and malaise, nausea and vomiting, and dreams/sleep were insomnia, headache, and fatigue. disorders. Adverse effects of at least moderate intensity reported in 5% or more of pediatric patients receiving abacavir for HIV-1 infection include fever and/or chills, nausea and vomiting, skin rash, and ear, nose, and throat infections.
In the treatment of HIV infection in adults, the most common reported adverse reactions (incidence >=15%) were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough. In the treatment of HIV infection in pediatric patients, the most common reported adverse reactions (incidence >=15%) were fever and cough. In the treatment of HBV infection, the most common reported adverse reactions (incidence >=10% and reported at a rate greater than placebo) were ear, nose, and throat infections; sore throat; and diarrhea.
There are 42 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hypersensitivity drug reaction |
Cough Hyperbilirubinemia Increased alanine transaminase Increased aspartate transaminase Kidney disease with reduction in glomerular filtration rate (GFr) Pharyngitis |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute hepatic failure Acute myocardial infarction Anaphylaxis Anemia Angioedema Aplastic anemia Eosinophilia Erythema multiforme Graves' disease Guillain-barre syndrome Hepatitis Hypersensitivity drug reaction Increased alanine transaminase Increased aspartate transaminase Increased creatine kinase level Lactic acidosis Lymphadenopathy Myositis Neutropenic disorder Pancreatitis Peripheral neuropathy Polymyositis Pure red cell aplasia Rhabdomyolysis Seizure disorder Skin rash Splenomegaly Steatosis of liver Stevens-johnson syndrome Suicidal Suicidal ideation Thrombocytopenic disorder Toxic epidermal necrolysis Urticaria |
There are 50 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Depression Diarrhea Dizziness Fatigue Gastritis Headache disorder Insomnia Malaise Migraine Nausea Skin rash Symptoms of anxiety Vertigo |
Acute abdominal pain Depression Diarrhea Dizziness Dream disorder Fever Flatulence Hypercholesterolemia Hyperglycemia Hypertriglyceridemia Nausea Pruritus of skin Vertigo Vomiting |
| Rare/Very Rare |
|---|
|
Alopecia Anorexia Arthralgia Conjunctivitis Dyspnea Elevated serum amylase Facial edema Fever General weakness Hepatitis Hyperglycemia Hyperlipidemia Hypertriglyceridemia Kidney disease with reduction in glomerular filtration rate (GFr) Malaise Muscle weakness Myalgia Paresthesia Pruritus of skin Stomatitis Symptoms of anxiety Weight gain Wheezing |
The following precautions are available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
Safety and efficacy of dolutegravir have not been established in pediatric Safety and efficacy of single-entity abacavir tablets or oral solution have been established in infants and children 3 months of age and older. Use of patients younger than 4 weeks of age or weighing <3 kg. In addition, safety abacavir in children 3 months of age and older is supported by and efficacy of the drug have not been established in pediatric patients pharmacokinetic trials and evidence from adequate and well-controlled who previously received another HIV integrase strand inhibitor (INSTI-experienced) and have HIV-1 with documented or suspected resistance trials in adult and pediatric patients.
Safety and efficacy have not been established in neonates and infants less than 3 months of age. to other HIV INSTIs (e.g., elvitegravir, raltegravir) Safety, efficacy, and pharmacokinetics of dolutegravir were evaluated in 75 HIV-1-infected, treatment-naive or treatment-experienced INSTI-naive pediatric patients 4 weeks to less than 18 years of age weighing at least 3 kg in an ongoing, open-label, multicenter, dose-finding clinical trial (IMPAACT P1093). In addition, pharmacokinetic data were evaluated in 2 weight-based pharmacokinetic substudies in an ongoing open-label, randomized, noninferiority trial evaluating safety, efficacy, and pharmacokinetics of dolutegravir in conjunction with 2 HIV NRTIs in HIV-1-infected pediatric patients younger than 18 years of age (ODYSSEY).
Effectiveness of dolutegravir observed in pediatric patients in the IMPAACT P1093 trial is comparable to that reported in treatment-experienced adults receiving the drug. Overall, safety data for dolutegravir in 75 pediatric patients 4 weeks to less than 18 years of age in the IMPAACT P1093 trial were comparable to those observed in adults receiving the drug. Pharmacokinetic parameters for dolutegravir reported in pediatric patients in the IMPAACT P1093 and ODYSSEY trials receiving weight-based dosages of the drug indicate that peak plasma concentrations and AUC are comparable to those in adults receiving 50 mg of dolutegravir once or twice daily.
Although mean peak plasma concentrations of dolutegravir are higher in pediatric patients, the increase is not considered clinically important since the safety profiles are similar in adult and pediatric patients. The safety and efficacy of lamivudine for the treatment of HIV-1 (Epivir(R)) have been established in pediatric patients 3 months of age and older. The scored tablet is the preferred formulation for HIV-1-infected pediatric patients weighing at least 14 kg for whom a solid dosage form is appropriate; in the ARROW trial, pediatric patients who received the oral solution had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more frequently. The safety and efficacy of lamivudine for the treatment of chronic HBV (Epivir-HBV(R)) in pediatric patients younger than 2 years of age have not been established.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety and efficacy have not been established in neonates and infants less than 3 months of age. to other HIV INSTIs (e.g., elvitegravir, raltegravir) Safety, efficacy, and pharmacokinetics of dolutegravir were evaluated in 75 HIV-1-infected, treatment-naive or treatment-experienced INSTI-naive pediatric patients 4 weeks to less than 18 years of age weighing at least 3 kg in an ongoing, open-label, multicenter, dose-finding clinical trial (IMPAACT P1093). In addition, pharmacokinetic data were evaluated in 2 weight-based pharmacokinetic substudies in an ongoing open-label, randomized, noninferiority trial evaluating safety, efficacy, and pharmacokinetics of dolutegravir in conjunction with 2 HIV NRTIs in HIV-1-infected pediatric patients younger than 18 years of age (ODYSSEY).
Effectiveness of dolutegravir observed in pediatric patients in the IMPAACT P1093 trial is comparable to that reported in treatment-experienced adults receiving the drug. Overall, safety data for dolutegravir in 75 pediatric patients 4 weeks to less than 18 years of age in the IMPAACT P1093 trial were comparable to those observed in adults receiving the drug. Pharmacokinetic parameters for dolutegravir reported in pediatric patients in the IMPAACT P1093 and ODYSSEY trials receiving weight-based dosages of the drug indicate that peak plasma concentrations and AUC are comparable to those in adults receiving 50 mg of dolutegravir once or twice daily.
Although mean peak plasma concentrations of dolutegravir are higher in pediatric patients, the increase is not considered clinically important since the safety profiles are similar in adult and pediatric patients. The safety and efficacy of lamivudine for the treatment of HIV-1 (Epivir(R)) have been established in pediatric patients 3 months of age and older. The scored tablet is the preferred formulation for HIV-1-infected pediatric patients weighing at least 14 kg for whom a solid dosage form is appropriate; in the ARROW trial, pediatric patients who received the oral solution had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more frequently. The safety and efficacy of lamivudine for the treatment of chronic HBV (Epivir-HBV(R)) in pediatric patients younger than 2 years of age have not been established.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral agents, including abacavir, the Antiretroviral Pregnancy Registry (APR) was established. Clinicians are encouraged to contact the registry at 800-258-4263 to report cases of prenatal exposure to antiretroviral drugs. Based on prospective reports to the APR of exposures to abacavir during pregnancy resulting in live births (including over 1,300 exposed in the first trimester and over 1,300 exposed in the second/third trimester), there was no difference between the overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7%
in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
Use of the MACDP population as the comparator group has several limitations; the MACDP assesses populations from a limited geographic area and does not include outcomes for births that occurred at <20 weeks' gestation. The rate of miscarriage is not reported in the APR. Abacavir crosses the placenta and is distributed into cord blood in concentrations similar to maternal serum concentrations.
Concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery. In animal reproductive studies, abacavir administration during organogenesis resulted in developmental toxicities (i.e., depressed fetal body weight, reduced crown-rump length) and fetal malformations (i.e., fetal anasarca, skeletal malformations) based on abacavir exposure 35 times the usual human exposure (based on AUC). No developmental effects were observed at exposures 3.5-times
the usual human exposure (based on AUC). The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to dolutegravir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
Data regarding the use of dolutegravir in pregnant women are insufficient to date to definitively assess a drug-associated risk for birth defects and miscarriage; however, human data from the APR do not indicate an increased birth defect risk. Of 1,377 dolutegravir exposures during pregnancy resulting in live births, the prevalence of birth defects was 3.3% following first trimester exposure and 5% following second-/third-trimester exposure.
There has been a concern regarding the development of neural tube defects in infants exposed to dolutegravir during pregnancy. The first interim analysis from an ongoing birth outcome surveillance study in Botswana identified an association between dolutegravir and an increased risk of neural tube defects when dolutegravir was administered at the time of conception and in early pregnancy. In a larger subsequent analysis, the prevalence of neural tube defects in infants delivered to individuals taking dolutegravir at conception was 0.11%,
which did not differ significantly from that of infants delivered to HIV-positive individuals not administered dolutegravir (0.11%) or to HIV-negative individuals (0.06%). Results from an Eswatini birth outcome surveillance study revealed similar outcomes; the prevalence of neural tube defects in infants delivered to individuals taking dolutegravir at conception was 0.08%, which did not differ significantly from that of infants delivered to individuals taking non-dolutegravir-containing regimens (0.22%) or to HIV-negative individuals (0.08%).
Lamivudine crosses the placenta and is distributed into cord blood in concentrations similar to maternal serum concentrations. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral agents, including lamivudine, the Antiretroviral Pregnancy Registry was established. Clinicians are encouraged to contact the registry at 800-258-4263 or https://www.apregistry.com/
to report cases of prenatal exposure to antiretroviral agents. Data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects for lamivudine compared with the background rate for major birth defects in the US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Reproduction studies in rats or rabbits using oral lamivudine dosages that resulted in plasma concentrations up to approximately 35 times higher than plasma concentrations attained with the recommended human dosage used for the treatment of HIV infection in adults have not revealed evidence of teratogenicity. Although there was evidence of early embryolethality in rabbits at exposure levels similar to those observed in humans, this effect was not seen in rats at exposure levels up to 35 times higher than those in humans.
in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
Use of the MACDP population as the comparator group has several limitations; the MACDP assesses populations from a limited geographic area and does not include outcomes for births that occurred at <20 weeks' gestation. The rate of miscarriage is not reported in the APR. Abacavir crosses the placenta and is distributed into cord blood in concentrations similar to maternal serum concentrations.
Concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery. In animal reproductive studies, abacavir administration during organogenesis resulted in developmental toxicities (i.e., depressed fetal body weight, reduced crown-rump length) and fetal malformations (i.e., fetal anasarca, skeletal malformations) based on abacavir exposure 35 times the usual human exposure (based on AUC). No developmental effects were observed at exposures 3.5-times
the usual human exposure (based on AUC). The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to dolutegravir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
Data regarding the use of dolutegravir in pregnant women are insufficient to date to definitively assess a drug-associated risk for birth defects and miscarriage; however, human data from the APR do not indicate an increased birth defect risk. Of 1,377 dolutegravir exposures during pregnancy resulting in live births, the prevalence of birth defects was 3.3% following first trimester exposure and 5% following second-/third-trimester exposure.
There has been a concern regarding the development of neural tube defects in infants exposed to dolutegravir during pregnancy. The first interim analysis from an ongoing birth outcome surveillance study in Botswana identified an association between dolutegravir and an increased risk of neural tube defects when dolutegravir was administered at the time of conception and in early pregnancy. In a larger subsequent analysis, the prevalence of neural tube defects in infants delivered to individuals taking dolutegravir at conception was 0.11%,
which did not differ significantly from that of infants delivered to HIV-positive individuals not administered dolutegravir (0.11%) or to HIV-negative individuals (0.06%). Results from an Eswatini birth outcome surveillance study revealed similar outcomes; the prevalence of neural tube defects in infants delivered to individuals taking dolutegravir at conception was 0.08%, which did not differ significantly from that of infants delivered to individuals taking non-dolutegravir-containing regimens (0.22%) or to HIV-negative individuals (0.08%).
Lamivudine crosses the placenta and is distributed into cord blood in concentrations similar to maternal serum concentrations. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral agents, including lamivudine, the Antiretroviral Pregnancy Registry was established. Clinicians are encouraged to contact the registry at 800-258-4263 or https://www.apregistry.com/
to report cases of prenatal exposure to antiretroviral agents. Data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects for lamivudine compared with the background rate for major birth defects in the US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Reproduction studies in rats or rabbits using oral lamivudine dosages that resulted in plasma concentrations up to approximately 35 times higher than plasma concentrations attained with the recommended human dosage used for the treatment of HIV infection in adults have not revealed evidence of teratogenicity. Although there was evidence of early embryolethality in rabbits at exposure levels similar to those observed in humans, this effect was not seen in rats at exposure levels up to 35 times higher than those in humans.
Abacavir is distributed into human milk. The effects of abacavir on the breastfed infant, or the effects of the drug on milk production are not known. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk.
Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. Dolutegravir is distributed into human milk. It is not known whether dolutegravir affects human milk production or affects the breast-fed infant.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant.
Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. Lamivudine is distributed into milk in humans.
It is not known whether the drug affects human milk production or affects the breast-fed infant. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding.
During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. If lamivudine is being used for treatment of chronic HBV infection, the benefits of breast-feeding and the importance of lamivudine to the woman should be considered along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk.
Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. Dolutegravir is distributed into human milk. It is not known whether dolutegravir affects human milk production or affects the breast-fed infant.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant.
Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. Lamivudine is distributed into milk in humans.
It is not known whether the drug affects human milk production or affects the breast-fed infant. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding.
During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. If lamivudine is being used for treatment of chronic HBV infection, the benefits of breast-feeding and the importance of lamivudine to the woman should be considered along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
Experience in patients >=65 years of age is insufficient to determine While clinical experience to date has not revealed age-related differences in response to abacavir, clinical studies evaluating abacavir have not whether they respond differently to dolutegravir than younger adults. Use dolutegravir with caution in geriatric patients because of age-related included sufficient numbers of adults 65 years of age or older to determine decreases in hepatic, renal, and/or cardiac function and potential for whether geriatric patients respond differently than younger adults. Dosage concomitant disease and drug therapy.
of abacavir for geriatric patients should be selected carefully because of limited experience with the drug in this age group and because these individuals frequently have decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. Clinical trials of lamivudine (Epivir(R) and Epivir-HBV(R)) did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently from younger subjects. Use caution when administering lamivudine to geriatric patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
of abacavir for geriatric patients should be selected carefully because of limited experience with the drug in this age group and because these individuals frequently have decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. Clinical trials of lamivudine (Epivir(R) and Epivir-HBV(R)) did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently from younger subjects. Use caution when administering lamivudine to geriatric patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
The following prioritized warning is available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine):
WARNING: In some people, the abacavir in this product has caused a serious (sometimes fatal) allergic reaction. Your doctor should order a blood test to measure your risk before you start this medication or take it again. If the blood test shows you are at greater risk, you should not take this medication and your doctor should discuss other treatment choices with you.
Symptoms of an allergic reaction may include any of the following: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing, fever, extreme tiredness, nausea, vomiting, diarrhea, stomach pain, muscle aches/pain, joint pain, sore throat, mouth sores, blisters, eye redness/swelling, or cough. Get medical help right away if you experience any of these symptoms. If you have stopped taking abacavir because of an allergic reaction, you must never take any form of abacavir again, or death could result.
Tell all of your doctors and pharmacists if you have stopped taking abacavir due to an allergic reaction. Also, properly throw away any unused medications containing abacavir. Read the warning card provided with this medication for more details.
You should be tested for hepatitis B infection before starting this medication. If you have hepatitis B infection and HIV, you may need additional drugs to treat the hepatitis B infection. You may also have a serious worsening of hepatitis symptoms if you stop taking lamivudine.
Talk with your doctor before stopping this medication. Your doctor will monitor liver tests for several months after you stop lamivudine. Get medical help right away if you develop symptoms of worsening liver problems.
WARNING: In some people, the abacavir in this product has caused a serious (sometimes fatal) allergic reaction. Your doctor should order a blood test to measure your risk before you start this medication or take it again. If the blood test shows you are at greater risk, you should not take this medication and your doctor should discuss other treatment choices with you.
Symptoms of an allergic reaction may include any of the following: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing, fever, extreme tiredness, nausea, vomiting, diarrhea, stomach pain, muscle aches/pain, joint pain, sore throat, mouth sores, blisters, eye redness/swelling, or cough. Get medical help right away if you experience any of these symptoms. If you have stopped taking abacavir because of an allergic reaction, you must never take any form of abacavir again, or death could result.
Tell all of your doctors and pharmacists if you have stopped taking abacavir due to an allergic reaction. Also, properly throw away any unused medications containing abacavir. Read the warning card provided with this medication for more details.
You should be tested for hepatitis B infection before starting this medication. If you have hepatitis B infection and HIV, you may need additional drugs to treat the hepatitis B infection. You may also have a serious worsening of hepatitis symptoms if you stop taking lamivudine.
Talk with your doctor before stopping this medication. Your doctor will monitor liver tests for several months after you stop lamivudine. Get medical help right away if you develop symptoms of worsening liver problems.
The following icd codes are available for TRIUMEQ (abacavir sulfate/dolutegravir sodium/lamivudine)'s list of indications:
| HIV infection | |
| B20 | Human immunodeficiency virus [HIv] disease |
| B97.35 | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | Asymptomatic human immunodeficiency virus [HIv] infection status |
Formulary Reference Tool