Triumeq Pd (abacavir sulfate/dolutegravir sodium/lamivudine)
Abacavir Oral Tablet For Suspension
Last reviewed · Source: First Databank (FDB) drug data
Overview
Dolutegravir sodium, an antiretroviral agent, is a human immunodeficiency virus (HIV) integrase strand transfer inhibitor (INSTI).
Lamivudine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI) that is active against HIV and hepatitis B virus (HBV).
Abacavir, an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI).
Dolutegravir sodium, an antiretroviral agent, is a human immunodeficiency virus (HIV) integrase strand transfer inhibitor (INSTI). Dolutegravir binds to the active site of HIV integrase and blocks the strand transfer step of retroviral DNA integration, which is essential for HIV replication. The drug is active against HIV type 1 (HIV-1) and also has in vitro activity against HIV type 2 (HIV-2).
Dolutegravir is not active against hepatitis C virus (HCV).
Dolutegravir-resistant HIV-1 has been produced in vitro and has emerged during dolutegravir therapy. In initial clinical studies in antiretroviral-naive patients, dolutegravir treatment was not associated with emergence of INSTI resistance. Treatment-emergent INSTI resistance has been reported when dolutegravir was used in clinical studies in antiretroviral-experienced patients who had not previously received an INSTI (INSTI-naive) or patients who had previously received an INSTI (INSTI-experienced), including some patients with historical genotypic evidence of INSTI-resistance substitutions or phenotypic evidence of resistance to other INSTIs (elvitegravir, raltegravir).
In some studies, treatment-emergent INSTI resistance was reported less frequently in those who received dolutegravir than those who received raltegravir, and it has been suggested that dolutegravir may possess a higher barrier to resistance than elvitegravir and raltegravir. Evidence of dolutegravir resistance substitutions has been reported in clinical studies of patients with confirmed virologic failure.
Although there is some evidence that dolutegravir has a different resistance profile than other HIV INSTIs and has been active in vitro against some HIV-1 strains resistant to other INSTIs (e.g., elvitegravir, raltegravir), cross-resistance between dolutegravir and other INSTIs (e.g., elvitegravir and/or raltegravir) has been reported. Dolutegravir has been active against HIV-1 resistant to HIV nucleoside reverse transcriptase inhibitors (NRTIs), HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs), or HIV protease inhibitors (PIs).
Following oral administration of dolutegravir 50 mg as conventional tablets once or twice daily, peak plasma concentrations of the drug are attained 1-3 hours after a dose; steady state is achieved within approximately 5 days when a once-daily regimen is used. Although studies using dolutegravir tablets indicate that food increases the extent and decreases the rate of oral absorption of the drug, dolutegravir may be taken with or without food. Dolutegravir tablets and dolutegravir tablets for oral suspension are not bioequivalent; the relative bioavailability of dolutegravir tablets for oral suspension is approximately 1.6-fold higher than that of dolutegravir conventional tablets.
Studies in HIV-1-infected pediatric patients 4 weeks to less than 18 years of age indicate that peak plasma concentrations and AUC reported with weight-based dolutegravir dosages of the tablets for oral suspension or conventional tablets are comparable to those in adults receiving 50 mg of the drug once or twice daily.
In vitro studies indicate that dolutegravir is approximately 99% bound to plasma proteins. Dolutegravir is distributed into cerebrospinal fluid; the clinical importance of this is unknown. Dolutegravir is metabolized primarily by uridine diphosphate-glucuronosyltransferase (UGT) 1A1; cytochrome P-450 (CYP) isoenzyme 3A plays only a minor role in metabolism of the drug.
Results of a meta-analysis of healthy individuals indicate that those with UGT1A1 genotypes that confer poor dolutegravir metabolism have a 32% lower clearance of dolutegravir and a 46% higher area under the plasma concentration-time curve (AUC) of the drug compared with those with genotypes associated with normal metabolism via UGT1A1. Following a single oral dose, 53% is excreted as unchanged drug in the feces and 31% is eliminated in urine (<1% as unchanged drug). Dolutegravir has a terminal half-life of approximately 14 hours.
Lamivudine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitor (NRTI). Following conversion to a pharmacologically active metabolite, lamivudine apparently inhibits replication of human retroviruses by interfering with viral RNA-directed DNA polymerase (reverse transcriptase). Lamivudine, therefore, exerts a virustatic effect against retroviruses by acting as a reverse transcriptase inhibitor.
Like other HIV nucleoside reverse transcriptase agents and other nucleoside antiviral agents, the antiviral activity of lamivudine appears to depend on intracellular conversion of the drug to a 5'-triphosphate metabolite; thus, 2',3'-dideoxy,3'-thiacytidine-5'-triphosphate (3TC-TP) and not unchanged lamivudine appears to be the pharmacologically active form of the drug. 3TC-TP is a structural analog of deoxycytidine triphosphate (dC-TP), the natural substrate for reverse transcriptase (viral RNA-directed DNA polymerase). Although other mechanisms may be involved in the antiretroviral activity of the drug, 3TC-TP appears to compete with naturally occurring dC-TP for incorporation into viral DNA by reverse transcriptase.
Following incorporation of 3TC-TP into the viral DNA chain instead of dC-TP, viral DNA synthesis is terminated prematurely because the absence of a 3'-hydroxy group on the oxathiolane ring prevents further 5' to 3' phosphodiester linkages.
Lamivudine is rapidly absorbed from the GI tract in patients with HIV or hepatitis B virus (HBV) infection. In HIV-infected patients or healthy individuals, peak plasma concentrations are achieved within 0.5-2 hours after a single dose. The absolute bioavailability of lamivudine 150-mg scored tablets and oral solution in adults is similar (86 and 87%, respectively).
In a crossover study in healthy adults evaluating the steady-state pharmacokinetics of lamivudine administered in a once-daily regimen (300-mg tablet once daily) or twice-daily regimen (150-mg tablet twice daily), AUC was similar with both regimens; however, peak plasma concentrations were 66% higher and trough concentrations were 53% lower with the once-daily regimen compared with the twice-daily regimen.
The absolute bioavailability of lamivudine tablets and lamivudine oral solution is lower in children than in adults. In addition, the relative bioavailability of the oral solution is approximately 40% lower than that of the tablets in children, despite no difference between the preparations in adults. It has been suggested that lower lamivudine exposures reported in pediatric patients receiving lamivudine oral solution are likely due to an interaction between lamivudine and concomitant solutions containing sorbitol (e.g., abacavir oral solution).
Data from pharmacokinetic studies evaluating once- and twice-daily lamivudine regimens in HIV-1-infected pediatric patients 3 months through 12 years of age indicate that AUCs attained with once-daily regimens were similar to those attained with twice-daily regimens when comparing the dosage regimens within the same formulation (i.e., either tablets or the oral solution). However, mean peak plasma concentrations were approximately 80-90% higher with once-daily lamivudine regimens compared with twice-daily lamivudine regimens.
Pharmacokinetics of lamivudine in pregnant women are similar to those reported in nonpregnant adults and postpartum women. Food does not appear to affect the AUC of lamivudine. In a small study in HIV-infected patients, peak plasma concentrations of lamivudine were decreased 40% and the rate of absorption was reduced when lamivudine was administered with food, but clinically important decreases in systemic availability of the drug (AUC) were not observed.
Lamivudine is distributed into CSF. In HIV-infected children who received oral lamivudine in a dosage of 8 mg/kg daily, CSF concentrations ranged from 0.04-0.3 mcg/mL and were 5.6-30.9% of concurrent serum concentrations. Lamivudine crosses the placenta and is distributed into cord blood and amniotic fluid.
Lamivudine concentrations in amniotic fluid are typically twofold higher than maternal serum concentrations and have ranged from 1.2-2.5 mcg/mL or 2.1-5.2 mcg/mL when lamivudine dosage in the mother was 150 or 300 mg twice daily, respectively. Lamivudine is distributed into milk. Lamivudine is less than 36% bound to plasma proteins.
Intracellularly, lamivudine is phosphorylated and converted by cellular enzymes to the active 5'-triphosphate metabolite. Lamivudine is not substantially metabolized by cytochrome P-450 (CYP) isoenzymes. Metabolism is a minor route of elimination of lamivudine; the only known metabolite is the trans-sulfoxide metabolite.
The majority of a lamivudine dose is eliminated unchanged in urine by active organic cationic secretion. Within 12 hours after an oral dose, approximately 5% is excreted in urine as the trans-sulfoxide metabolite. In single-dose studies in healthy individuals or patients with HIV or HBV infection, the mean plasma half-life of lamivudine was 5-7 hours.
The plasma half-life in HIV-infected children 4 months to 14 years of age is 2 hours.
The pharmacokinetics of lamivudine are not altered in patients with hepatic impairment. In patients with impaired renal function, peak plasma concentrations, AUC, and plasma half-life of lamivudine are increased. Hemodialysis increases lamivudine clearance; however, the length of time of hemodialysis (4 hours) is insufficient to substantially alter mean lamivudine exposure after a single dose of the drug.
Continuous ambulatory peritoneal dialysis and automated peritoneal dialysis have negligible effects on lamivudine clearance. There are no significant or clinically relevant racial or gender differences in lamivudine pharmacokinetics.
Following conversion to a pharmacologically active metabolite, abacavir inhibits replication of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), by interfering with viral RNA-directed DNA polymerase (reverse transcriptase). The drug, therefore, exerts a virustatic effect against retroviruses by acting as a reverse transcriptase inhibitor.
Like other HIV nucleoside reverse transcriptase inhibitors (NRTIs), including didanosine, emtricitabine, lamivudine, and zidovudine, the antiviral activity of abacavir is dependent upon intracellular conversion of the drug to a 5'-triphosphate metabolite. Carbovir triphosphate (carbocyclic guanosine triphosphate) appears to be the pharmacologically active form of the drug. Substantial differences exist in the rates at which human cells phosphorylate various NRTIs and in the enzymatic pathways involved.
Enzymatic conversion of abacavir to carbovir triphosphate is complex and involves certain steps and enzymes that differ from those involved in the enzymatic conversion of dideoxynucleoside reverse transcriptase inhibitors. Abacavir is phosphorylated by adenosine phosphotransferase to abacavir monophosphate, which is converted to carbovir monophosphate by a cytosolic enzyme. Subsequently, carbovir monophosphate is phosphorylated by cellular kinases to carbovir triphosphate.
Abacavir is not a substrate for enzymes (i.e., thymidine kinase, deoxycytidine kinase, adenosine kinase, mitochondrial deoxyguanosine kinase) known to phosphorylate other nucleoside analogs. Because phosphorylation of abacavir depends on cellular rather than viral enzymes, conversion of the drug to the active triphosphate derivative occurs in both virus-infected and uninfected cells. Carbovir triphosphate is a structural analog of deoxyguanosine-5'-triphosphate (dGTP), the usual substrate for viral RNA-directed DNA polymerase.
Although other mechanisms may be involved in the antiretroviral activity of the drug, carbovir triphosphate appears to compete with deoxyguanosine-5'-triphosphate for viral RNA-directed DNA polymerase and incorporation into viral DNA. Following incorporation of carbovir triphosphate into the viral DNA chain instead of deoxyguanosine-5'-triphosphate, DNA synthesis is prematurely terminated because the absence of the 3'-hydroxy group on the drug prevents further 5' to 3' phosphodiester linkages.
Abacavir is rapidly absorbed following oral administration, with similar AUCs observed following the use of the oral solution or tablets. The geometric mean absolute oral bioavailability of abacavir sulfate tablets is 83%. In HIV-infected adults receiving abacavir in a dosage of 300 mg twice daily (given as abacavir succinate), peak plasma concentration and AUC(0-12 hours) of the drug at steady-state averaged 3 mcg/mL and 6.02 mcg*hour/mL, respectively.
In studies in HIV-infected adults employing oral abacavir dosages of 300-1200 mg daily (given as abacavir succinate), the pharmacokinetics of the drug were independent of the dose. Administration of abacavir tablets either during a fasting or fed state does not significantly impact systemic exposure. In pediatric patients, abacavir exposure is expected to be similar regardless of whether the scored tablet or oral solution is administered.
According to the manufacturer, abacavir tablets and oral solution can be used interchangeably. After single and multi-dose regimens of abacavir oral solution at recommended dosages in pediatric subjects, serum concentrations of abacavir were similar to those in adult patients. In crossover studies of pediatric subjects 3 months to 12 years of age receiving abacavir and lamivudine, the use of abacavir oral solution and tablets given once daily resulted in similar exposure to abacavir given twice daily when the same total daily dosage was administered.
In these studies, the mean peak plasma concentrations of abacavir were approximately 1.6- to 2.3-fold higher when the same total daily abacavir dosage was administered once versus twice daily.
Abacavir is about 50% bound to plasma proteins; binding of abacavir to plasma proteins is independent of drug concentration. Abacavir is distributed into CSF. Following administration of radiolabeled abacavir, total blood- and plasma-drug related radioactivity are identical; these results indicate abacavir readily distributes into erythrocytes.
Following oral administration of a 600-mg dose of radiolabeled abacavir, 82.2% of the dose is excreted in urine and 16% of the dose is excreted in feces. The 5'-carboxylic acid metabolite, 5'-glucuronide metabolite, and unchanged abacavir accounted for 30, 36, and 1.2%, respectively, of recovered radioactivity in urine; unidentified minor metabolites accounted for 15% of recovered radioactivity in urine. Abacavir is metabolized by alcohol dehydrogenase to form the 5'-carboxylic acid and by glucuronyltransferase to form the 5'-glucuronide; these metabolites do not appear to have any antiviral activity.
Any involvement of cytochrome P-450 isoenzymes in the metabolism of abacavir is limited. The plasma elimination half-life of abacavir following a single oral dose (given as abacavir sulfate) is about 1.5 hours. Systemic exposure of abacavir is not affected by gender or race (Black vs white patients).
USES: This product contains 3 drugs: abacavir, dolutegravir, and lamivudine. It is used to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better.
This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life. Abacavir and lamivudine belong to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). Dolutegravir belongs to a class of drugs known as integrase inhibitors.
This medication is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor.
Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.
Generic name: abacavir sulfate/dolutegravir sodium/lamivudine
Pronunciation: (a-BAK-a-vir/DOE-loo-TEG-ra-vir/la-MIV-ue-deen)
Drug class: Abacavir
Therapeutic class: Anti-Infective Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Triumeq Pd:
- Hiv Infection
Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.
Dosing
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.
Abacavir is commercially available as abacavir sulfate; dosage is expressed in terms of abacavir.
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 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.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
The following drug interactions are based on studies using dolutegravir; refer to the full prescribing information for further details. Additional drug interactions exist for fixed-combinations containing abacavir, dolutegravir, and lamivudine (Triumeq(R)); dolutegravir and lamivudine (Dovato(R)); and dolutegravir and rilpivirine (Juluca(R)). When a fixed combination is used, consider the interactions associated with each drug in the fixed combination; see the full prescribing information for drug interactions of each combination product.
The following drug interactions are based on studies using lamivudine. Additional drug interactions may exist for fixed-dose combination products containing lamivudine/zidovudine (Combivir(R), generic) , abacavir/lamivudine (Epzicom(R), generic) , abacavir/lamivudine/zidovudine (Trizivir(R), generic) , lamivudine/tenofovir disoproxil fumarate (Cimduo(R)) , doravirine/lamivudine/tenofovir disoproxil fumarate (Delstrigo(R)) , dolutegravir/lamivudine (Dovato(R)) , efavirenz/lamivudine/tenofovir disoproxil fumarate (Symfi(R); Symfi(R) Lo) , and abacavir/dolutegravir/lamivudine (Triumeq(R); Triumeq PD(R)). See the full prescribing information for information on each of these combination products.
In vitro studies indicate that abacavir has the potential to inhibit cytochrome P-450 (CYP) isoenzyme 1A1, and has limited potential to inhibit CYP3A4. Abacavir does not induce nor inhibit CYP2C9 or CYP2D6. At therapeutic exposures, abacavir is not expected to affect substrates of organic anion transporter polypeptide (OATP)1B1 or OATP1B3, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic cation transporter (OCT)1, OCT2, or multidrug and toxic extrusion protein (MATE)1 and MATE2-K.
In vitro studies indicate that abacavir is a substrate of BCRP and P-gp; however, the concomitant use of modulators of these transporters is not expected to have clinically relevant effects on abacavir serum concentrations. In vitro studies indicate that abacavir is not a substrate of OATP1B1, OAP1B3, OCT1, OCT2, OAT1, MATE1, MATE2-K, or multidrug resistance-associated protein (MRP)2, or MRP4; therefore, the concomitant use of agents that modulate these transporters is not expected to affect abacavir serum concentrations.
The following drug interactions are based on studies using abacavir. Additional drug interactions may exist for fixed-dose combinations containing abacavir and lamivudine (Epzicom(R)); abacavir, lamivudine, and zidovudine (Trizivir(R)); and abacavir, dolutegravir, and lamivudine (Triumeq(R) and Triumeq PD(R)). See the full prescribing information for drug interactions of each of these combination products.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Anti-Retrovirals/Atidarsagene Autotemcel
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: 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)
Anti-Retrovirals/Elivaldogene Autotemcel
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: 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)
Anti-Retrovirals/Etuvetidigene Autotemcel
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: Etuvetidigene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating HIV-based lentiviral vector. Antiretrovirals may interfere with the manufacturing of the apheresed cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of etuvetidigene autotemcel.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Patients should not take antiretrovirals for at least one month prior to mobilization and until at least 7 days after etuvetidigene autotemcel infusion.(1) If a patient requires antiretroviral agents for HIV post-exposure prophylaxis, etuvetidigene autotemcel treatment should be delayed until HIV testing is negative at 6 months post-exposure.(1)
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of etuvetidigene autotemcel therapy.(1)
Anti-Retrovirals/Lovotibeglogene Autotemcel
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: 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)
Anti-Retrovirals; Hydroxyurea/Betibeglogene Autotemcel
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: 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)
Dolutegravir/Dofetilide
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)
Emtricitabine; Lamivudine/Islatravir
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: Emtricitabine and lamivudine may inhibit the intracellular phosphorylation of islatravir by deoxycytidine kinase (dCK).(1)
CLINICAL EFFECTS: Concurrent administration of emtricitabine or lamivudine with islatravir may result in decreased clinical efficacy of islatravir.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of the doravirine-islatravir fixed-dose combination states that co-administration with emtricitabine or lamivudine is contraindicated.(1)
DISCUSSION: Islatravir undergoes a series of phosphorylations to its active metabolites.(1) In a clinical study in healthy participants, co-administration of multiple daily doses of 300 mg lamivudine and a single dose of 2 mg islatravir (8 times the recommended dosage) decreased intracellular ISL-TP (islatravir active metabolite) area under the curve (AUC) level by 87% and maximum concentration (Cmax) by 76% relative to islatravir alone. A similar effect is anticipated when islatravir is co-administered with emtricitabine.(1,2) Compounds phosphorylated by dCK and linked to this monograph include: emtricitabine and lamivudine.
Lamivudine/Zalcitabine
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: Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of each other.(1-6)
CLINICAL EFFECTS: Concurrent administration of lamivudine and zalcitabine may result in decreased clinical efficacy of one or both agents.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and zalcitabine is not recommended.(1-3)
DISCUSSION: Both lamivudine(1-3) and zalcitabine(7) undergo a series of phosphorylations to their active metabolites. In an in vitro study, the presence of lamivudine significantly decreased the phosphorylation of zalcitabine, resulting in a 50% decrease in zalcitabine triphosphate levels.(4) In an in vitro study in peripheral blood mononuclear cells (PBMCs) and U937 cells, zalcitabine significantly inhibited the phosphorylation of lamivudine. No lamivudine triphosphate was found in the PBMCs and the amount of lamivudine triphosphate was decreased 33% when compared to control values in the U937 cell line.(5) In another in vitro study, lamivudine decreased total zalcitabine phosphates by 57%. There was no effect on lamivudine phosphorylation.(6)
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Abacavir/Riociguat
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.
Anti-Retrovirals/Marnetegragene Autotemcel
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Marnetegragene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of transduced cells.
CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of marnetegragene 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 antiretrovirals) 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.(1)
DISCUSSION: Antiretroviral medications may interfere with the manufacturing of marnetegragene autotemcel.(1)
Cimetidine; Dolutegravir/Dalfampridine
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)
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.
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 and etravirine 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 in patients without INSTI resistance, 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 patients with certain INSTI-associated resistance 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)
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)
Lamivudine/Sorbitol
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)
Moderate Interaction: Assess the risk to the patient and take action as needed.
Dolutegravir/Metformin
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)
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)
Oct2 Inhibitors/Cisplatin
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, brepocitinib, dolutegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(3)
Oct2 Inhibitors/Clofarabine
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, brepocitinib, cimetidine, dolutegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(5)
Oct2 Inhibitors/Oxaliplatin
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, brepocitinib, dolutegravir, givinostat, trilaciclib, and vimseltinib.(5)
Oct2 Inhibitors/Pindolol
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, brepocitinib, cimetidine, dolutegravir, givinostat, and vimseltinib.(3)
Oct2 Inhibitors/Procainamide
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, check procainamide and N-acetylprocainamide (NAPA) levels, monitor for toxicities of procainamide and consider dosage reduction of procainamide.(1) Since other H-2 antagonists (e.g., ranitidine, famotidine) do not appear to interact, substituting cimetidine with one of these agents may be desirable. However, if a patient is already receiving this combination and is not experiencing adverse effects, substitution is probably not necessary. 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, brepocitinib, cimetidine, dolutegravir, givinostat, isavuconazole, trilaciclib, tucatinib, and vimseltinib.(4)
Contraindications
*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.
- Acute pancreatitis
- Chronic pancreatitis
- HLa-B *57:01 positive
- Lactation
- Lactic acidosis
- Pancreatitis
- 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
- 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
Adverse reactions
In patients receiving dolutegravir in an adult clinical trial, the most common adverse effects of moderate to severe intensity and incidence >=2% were insomnia, headache, and fatigue.
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 adult patients receiving abacavir for HIV-1 infection include nausea, headache, fatigue and malaise, nausea and vomiting, and dreams/sleep 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.
More Frequent
- Elevated serum lipase
- Headache disorder
- Paresthesia
Less Frequent
- Acute abdominal pain
- Arthralgia
- Bronchitis
- Cough
- Drug fever
- Dyspnea
- Hyperbilirubinemia
- Hypersensitivity drug reaction
- Increased alanine transaminase
- Increased aspartate transaminase
- Kidney disease with reduction in glomerular filtration rate (GFr)
- Myalgia
- Neutropenic disorder
- Pharyngitis
- Skin rash
- Thrombocytopenic disorder
Rare or Very Rare
- Abnormal hepatic function tests
- Abnormal hepatic function tests
- Abnormal hepatic function tests
- Acute hepatic failure
- Acute myocardial infarction
- Acute respiratory distress syndrome
- Anaphylaxis
- Anaphylaxis
- Anemia
- Anemia
- Angioedema
- Anorexia
- Edema
- Eosinophilia
- Erythema multiforme
- Graves' disease
- Graves' disease
- Guillain-barre syndrome
- Guillain-barre syndrome
- Hepatitis
- Hepatitis
- Hepatomegaly
- Hypersensitivity drug reaction
- Hypotension
- Increased alanine transaminase
- Increased aspartate transaminase
- Lactic acidosis
- Lactic acidosis
- Lymphadenopathy
- Multiple organ failure
- Myositis
- Pancreatitis
- Pancreatitis
- Paresthesia
- Pneumonia
- Polymyositis
- Polymyositis
- Pure red cell aplasia
- Renal failure
- Rhabdomyolysis
- Sideroblastic anemia
- Skin rash
- Splenomegaly
- Steatosis of liver
- Steatosis of liver
- Stevens-johnson syndrome
- Suicidal
- Suicidal ideation
- Thrombocytopenic disorder
- Toxic epidermal necrolysis
More Frequent
- Cough
- Diarrhea
- Diarrhea
- Dream disorder
- Fatigue
- Fatigue
- Fatigue
- Fever
- Headache disorder
- Headache disorder
- Infection of ear
- Insomnia
- Lipodystrophy associated with human immunodeficiency virus infection
- Malaise
- Malaise
- Nausea
- Nausea
- Peripheral neuropathy
- Sleep disorder
- Sore throat
- Vomiting
Less Frequent
- Abdominal pain with cramps
- Acute abdominal pain
- Anorexia
- Arthralgia
- Chills
- Chills
- Depression
- Depression
- Diarrhea
- Dizziness
- Dizziness
- Dizziness
- Dream disorder
- Dyspepsia
- Flatulence
- Hypercholesterolemia
- Hyperglycemia
- Hyperlipidemia
- Hypertriglyceridemia
- Hypertriglyceridemia
- Insomnia
- Musculoskeletal pain
- Myalgia
- Nausea
- Pruritus of skin
- Rhinitis
- Symptoms of anxiety
- Upper respiratory infection
- Vertigo
- Vomiting
- Vomiting
Rare or Very Rare
- Alopecia
- Arthralgia
- Conjunctivitis
- Cramps
- Depression
- Facial edema
- Fever
- General weakness
- Hyperglycemia
- Hyperlipidemia
- Malaise
- Muscle weakness
- Myalgia
- Pruritus of skin
- Skin rash
- Stomatitis
- Symptoms of anxiety
- Urticaria
- Weight gain
- Wheezing
Precautions
No enhanced messaging available.
Safety and efficacy of dolutegravir have not been established in pediatric patients younger than 4 weeks of age or weighing <3 kg. In addition, safety and efficacy of the drug have not been established in pediatric patients who previously received another HIV integrase strand inhibitor (INSTI-experienced) and have HIV-1 with documented or suspected resistance 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.
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 abacavir in children 3 months of age and older is supported by pharmacokinetic trials and evidence from adequate and well-controlled trials in adult and pediatric patients. Safety and efficacy have not been established in neonates and infants less than 3 months of age.
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.
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).
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.
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.
The manufacturer makes no specific dosage recommendations in geriatric patients, but recommends caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Use with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
The manufacturer makes no specific dosage recommendations for single-entity abacavir in geriatric patients. Select dosage with caution due to age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Experience in patients >=65 years of age is insufficient to determine whether they respond differently to dolutegravir than younger adults. Use dolutegravir with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and potential for 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.
While clinical experience to date has not revealed age-related differences in response to abacavir, clinical studies evaluating abacavir have not included sufficient numbers of adults 65 years of age or older to determine whether geriatric patients respond differently than younger adults. Dosage 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.
ICD codes
| Code | Type | Description |
|---|---|---|
| HIV infection | ||
| B20 | ICD10CM | Human immunodeficiency virus [HIv] disease |
| B97.35 | ICD10CM | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | ICD10CM | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | ICD10CM | Asymptomatic human immunodeficiency virus [HIv] infection status |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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