Indicated for:

Adult Patients:

TYBOST is a CYP3A inhibitor indicated to increase systemic exposure of atazanavir or darunavir (once daily dosing regimen) in combination with other antiretroviral agents in the treatment of HIV-1 infection in adults.

Pediatric Patients:

TYBOST is a CYP3A inhibitor indicated to increase systemic exposure of atazanavir or darunavir (once daily dosing regimen) in combination with other antiretroviral agents in the treatment of HIV-1 infection in pediatric patients:

• weighing at least 35 kg co-administered with atazanavir or
• weighing at least 40 kg co-administered with darunavir

TYBOST is not interchangeable with ritonavir to increase systemic exposure of darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data. The use of TYBOST is not recommended with darunavir 600 mg twice daily, fosamprenavir, saquinavir, or tipranavir.

Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain TYBOST interactions. TYBOST and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications.

Administer TYBOST in conjunction with atazanavir or darunavir and other antiretroviral agents in the treatment of adults and pediatric patients with HIV-1 infection. TYBOST must be co-administered at the same time as atazanavir or darunavir.

Prior to or when initiating TYBOST and during treatment with TYBOST, on a clinically appropriate schedule, assess estimated creatinine clearance because TYBOST decreases estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. When co-administering TYBOST with TDF, assess estimated creatinine clearance, urine glucose, and urine protein at baseline. In patients with chronic kidney disease, also assess serum phosphorus.

TYBOST co-administered with tenofovir DF is not recommended in patients who have an estimated creatinine clearance below 70 mL/min because dose adjustment of tenofovir DF is required below 50 mL/min and such dose adjustments have not been established for co-administration with TYBOST.

Co-administration of TYBOST and TDF in combination with concomitant or recent use of a nephrotoxic agent is not recommended.

Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported when TYBOST was used in an antiretroviral regimen that contained tenofovir DF.

Initiation of TYBOST, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A, or initiation of medications metabolized by CYP3A in patients already receiving TYBOST, may increase plasma concentrations of medications metabolized by CYP3A and reduce plasma concentrations of active metabolite(s) formed by CYP3A. Initiation of medications that inhibit or induce CYP3A may respectively increase or decrease concentrations of TYBOST with atazanavir or darunavir.

The concomitant use of TYBOST with atazanavir or darunavir and the following drugs is contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect: alfuzosin, ranolazine, dronedarone, carbamazepine, phenobarbital, phenytoin, colchicine, rifampin, irinotecan (contraindicated with TYBOST co-administered with atazanavir only), lurasidone, pimozide, dihydroergotamine, ergotamine, methylergonovine, St. John’s wort, lovastatin, simvastatin, drospirenone/ethinyl estradiol (contraindicated with TYBOST co-administered with atazanavir only), nevirapine (contraindicated with TYBOST co-administered with atazanavir only), sildenafil when administered as Revatio for the treatment of pulmonary arterial hypertension, indinavir (contraindicated with TYBOST co-administered with atazanavir only), triazolam, and orally administered midazolam.

The following antiretrovirals are not recommended in combination with TYBOST because dosing recommendations for such combinations have not been established and co-administration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance:

• More than one antiretroviral that requires pharmacokinetic enhancement (i.e., two protease inhibitors or a protease inhibitor in combination with elvitegravir)
• Darunavir in combination with efavirenz, nevirapine, or etravirine
• Atazanavir in combination with etravirine
• Atazanavir in combination with efavirenz in treatment-experienced patients
• Darunavir 600 mg twice daily
• Other HIV-1 protease inhibitors including fosamprenavir, saquinavir, or tipranavir
• TYBOST in combination with fixed-dose combination tablets that contain cobicistat is not recommended.
• TYBOST in combination with lopinavir/ritonavir or regimens containing ritonavir is not recommended due to similar effects of TYBOST and ritonavir on CYP3A

TYBOST interacts with certain oral contraceptives.

Maraviroc is a substrate of CYP3A. When co-administered with maraviroc, patients should receive maraviroc 150 mg twice daily. 

Due to potentially increased bleeding risk, dosing recommendations for co-administration of apixaban with TYBOST depends on the apixaban dose.

When co-administering with SSRIs, TCAs, or trazodone, careful dose titration of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response are recommended.

Due to potentially increased bleeding risk, dosing recommendations for co-administration of betrixaban, dabigatran, or edoxaban with a P-gp inhibitor such as TYBOST co-administered with atazanavir depends on DOAC indication and renal function.

Co-administration with voriconazole is not recommended unless the benefit/risk assessment justifies the use of voriconazole.

Clinical monitoring is recommended for co-administration with beta-blockers that are metabolized by CYP2D6.

Clinical monitoring is recommended for co-administration with calcium channel blockers metabolized by CYP3A.

Co-administration with parenteral midazolam may increase plasma concentrations of midazolam. 

Co-administration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to atazanavir or darunavir. Consider alternative corticosteroids.

Co-administration with corticosteroids (all routes of administration) whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression.

Discontinue use of bosentan at least 36 hours prior to initiation of TYBOST co-administered with atazanavir or darunavir. After at least 10 days following the initiation of TYBOST combined with atazanavir or darunavir, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability.

Careful monitoring of therapeutic and adverse effects of fentanyl (including potentially fatal respiratory depression) is recommended with co-administration.

A dose decrease may be needed for tramadol with concomitant use.

TYBOST co-administered with darunavir or atazanavir should not be initiated in pregnant individuals. An alternative regimen is recommended for individuals who become pregnant during therapy with TYBOST co-administered with darunavir or atazanavir.

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.

GoToSource

• Use in patients weighing less than 35 kg. GoToSource

Gastrointestinal toxicity, diarrhea, vomiting, rash, ocular icterus, abnormal dreams, nightmares, fatigue, upper respiratory infection, depression and elevated creatinine. GoToSource

Acute kidney failure and fanconi syndrome (disorder of kidney tubule function). GoToSource

Hyperglycaemia (high blood sugar). GoToSource

Hyperbilirubinemia (excess bilirubin in blood). GoToSource

No major injury lawsuits reported.