Version May 2024
HIV-1 infection, treatment: Oral: 600 mg twice daily, in combination with other antiretrovirals (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
Hepatoxicity has been associated with antiretroviral combination therapy, particularly among patients coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Increased serum alanine aminotransferase (ALT) and increased serum aspartate aminotransferase (AST) have been reported with fostemsavir, including severe (grade 3 or 4); some of these elevations were consistent with reactivation of HBV.
Mechanism: Liver enzyme elevations associated with antiretroviral combination therapy in the setting of chronic viral hepatitis may be part of an immune-restoration disease (Ref).
Onset: Varied; in a prospective cohort study of hepatotoxicity associated with antiretroviral therapy (not including fostemsavir), median onset to antiretroviral-induced severe hepatoxicity was 118 days (range: 63 to 156 days) (Ref). In general, the risk for developing liver enzyme elevations due to antiretroviral therapy is greatest during the first few months following therapy initiation (Ref).
Risk factors:
Antiretroviral combination therapy in general:
• Chronic HBV and/or HCV coinfection (Ref)
• Higher baseline ALT/AST levels (Ref)
• Females (Ref)
Immune reconstitution syndrome has been reported with combination antiretroviral therapy, including fostemsavir. Immune reconstitution inflammatory syndrome (IRIS) typically results from an inflammatory response to an infectious agent, such as an indolent or residual opportunistic infection (OI) (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, tuberculosis). Immune reconstitution has also been associated with activation of certain autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barre syndrome, autoimmune hepatitis) and other noninfectious etiologies (Ref).
Mechanism: Non-dose-related; immunologic. Believed to result from an exaggerated activation of the immune system against persisting antigen (paradoxical) or viable pathogens (unmasking) in the setting of improved immunologic function (ie, a response to antiretroviral therapy); innate immunity has also been implicated (Ref).
Onset: Varied; in most cases, IRIS appears during the first 3 months after initiation of combination antiretroviral therapy (“early IRIS”); however, it can appear later, generally 3 to 12 months after therapy initiation (“late IRIS”). In a few cases, it may occur up to 4 years later (Ref). In the setting of immune reconstitution associated with autoimmune disorders, onset is more variable and can occur many months after therapy initiation.
Risk factors:
• Current or past history of OI
•· Very low CD4 cell count (<100 cells/mcL) at the time of antiretroviral treatment initiation (Ref)
Prolonged QT interval on ECG has been reported with fostemsavir at supratherapeutic doses. Data suggest that clinically significant effects on the QTc interval are unlikely with therapeutic dosing of fostemsavir (Ref).
Mechanism: Dose-related (Ref)
Risk factors:
• Higher than recommended dosage (eg, 4 times the recommended daily dose [4,800 mg/day])
• History of prolonged QT interval or relevant preexisting cardiac disease (potential risk factor for QTcprolongation in general)
• Coadministration with drugs known to cause QT prolongation (potential risk factor for QTc prolongation in general)
• Older age (potential risk factor for QTc prolongation in general)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency of adverse events is as reported in adults receiving combination antiretroviral therapy.
>10%: Renal: Increased serum creatinine (grades 3/4: 19%)
1% to 10%:
Cardiovascular: Increased serum creatine kinase (grades 3/4: 2%), prolonged QT interval on ECG (asymptomatic, per manufacturer’s labeling)
Dermatologic: Pruritus, skin rash (3%)
Endocrine & metabolic: Hypercholesterolemia (grade 3: 5%), hyperglycemia (grades 3/4: 4%), increased LDL cholesterol (grades 3/4: 4%), increased serum triglycerides (grades 3/4: 5%), increased uric acid (grades 3/4: 3%)
Gastrointestinal: Abdominal pain (3%), diarrhea (4%), dysgeusia, dyspepsia (3%), increased serum lipase (grades 3/4: 5%), nausea (10%), vomiting (2%)
Hematologic & oncologic: Decreased hemoglobin (grades 3/4: 6%), decreased neutrophils (grades 3/4: 4%), leukocyte disorder (grades 3/4: 1%)
Hepatic: Increased direct serum bilirubin (grade 3: 7%), increased serum alanine aminotransferase (grades 3/4: 3% to 5%), increased serum aspartate aminotransferase (grades 3/4: 2% to 4%), increased serum bilirubin (grades 3/4: 3%)
Immunologic: Immune reconstitution syndrome (2%)
Nervous system: Dizziness, drowsiness (2%), fatigue (3%), headache (4%), peripheral neuropathy, peripheral sensory neuropathy, sleep disturbance (3%)
Neuromuscular & skeletal: Myalgia
Frequency not defined: Infection: Infection (Kozal 2020), reactivation of HBV
Hypersensitivity to fostemsavir or any component of the formulation; concomitant use of strong CYP3A inducers (eg, enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, St John’s wort).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Disease-related concerns:
• Hepatitis B virus coinfection: Initiate and/or maintain effective anti–hepatitis B virus (HBV) therapy in patients coinfected with HBV.
Special populations:
• Older adult: Adverse effects may be increased in elderly patients.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 12 Hour, Oral, as tromethamine:
Rukobia: 600 mg
No
Tablet, 12-hour (Rukobia Oral)
600 mg (per each): $180.20
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 12 Hour, Oral, as tromethamine:
Rukobia: 600 mg
Oral: Administer with or without food. Swallow tablets whole; do not chew, crush, or split tablets.
HIV-1 infection, treatment: Treatment of HIV-1 infection, in combination with other antiretrovirals, in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen.
Fostemasavir may be confused with fosamprenavir.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, OATP1B1/1B3 (SLCO1B1/1B3)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Fostemsavir. Risk X: Avoid combination
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification
Ethinyl Estradiol-Containing Products: Fostemsavir may increase the serum concentration of Ethinyl Estradiol-Containing Products. Management: Ethinyl estradiol daily dose should not exceed 30 mcg during coadministration with fostemsavir. Monitor patients closely for any evidence of a thromboembolism. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors (Statins): Fostemsavir may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Methadone: Fostemsavir may enhance the QTc-prolonging effect of Methadone. Fostemsavir may increase the serum concentration of Methadone. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
St John's Wort: May decrease serum concentrations of the active metabolite(s) of Fostemsavir. Risk X: Avoid combination
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
Contraception is not required to initiate or continue antiretroviral therapy.
The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend fostemsavir for patients with HIV infection who are not yet pregnant but are trying to conceive.
Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
Data collected by the antiretroviral pregnancy registry are insufficient to evaluate human teratogenic risk.
In general, maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm birth, low birthweight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.
The Health and Human Services (HHS) perinatal HIV guidelines do not recommend fostemsavir as initial therapy for pregnant patients with HIV who are antiretroviral naïve; data are insufficient to recommend fostemsavir for pregnant patients with HIV who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Consider switching if pregnancy occurs during fostemsavir therapy. Highly treatment experienced patients who become pregnant while taking fostemsavir may continue if other therapeutic alternatives are not available; frequent viral load monitoring is recommended. Data collected by the antiretroviral pregnancy registry are insufficient to make dosing recommendations.
ART is recommended for all pregnant people with HIV to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.
Health care providers caring for pregnant patients with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
It is not known if fostemsavir is present in breast milk.
Maintaining maximum viral suppression during pregnancy and postpartum decreases but does not eliminate the risk of HIV transmission via breast milk. In addition, multiclass-resistant virus has been detected in breastfeeding infants who acquire HIV despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients with HIV when safer infant feeding options are available. Persons with HIV who maintain an undetectable viral load while taking antiretroviral therapy (ART) should evaluate infant feeding options (formula, banked donor milk, or breastfeeding) as part of a shared decision-making process (if breastfeeding is being considered, see guidelines for measures to reduce the risk of HIV transmission). When the HIV status at delivery is not known, breast milk may be expressed and stored until a negative test is available. If HIV infection is diagnosed after breastfeeding has been initiated, breastfeeding should be discontinued immediately. Breastfeeding is not recommended for persons with HIV who are not taking ART and/or who do not have sustained viral suppression.
Information is available for counseling and managing patients with HIV who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2023).
CD4 count, HIV RNA plasma levels; hepatic transaminases in hepatitis B virus and/or hepatitis C virus coinfected patients.
Fostemsavir is hydrolyzed to the active moiety, temsavir, which is a gp120 attachment inhibitor. Temsavir binds to the HIV-1 envelope protein gp120 subunit and selectively inhibits the interaction between the virus and cellular CD4 receptors, preventing host cell attachment. In addition, temsavir can inhibit gp120-dependent postattachment steps required for viral entry into host cells.
Absorption: Administration with a high-fat meal (~985 calories, 60% fat) increases drug exposure compared to fasting (AUC ratio 1:81).
Distribution: Vd: 29.5 L.
Protein binding: 88.4%.
Metabolism: Hydrolysis (esterases) (36.1%); oxidation (CYP3A4) (21.2%); UGT (<1%).
Bioavailability: 26.9%.
Half-life elimination: 11 hours.
Time to peak: 2 hours.
Excretion: Urine: 51% (<2% as unchanged drug); feces: 33% (1.1% as unchanged drug).
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