Version May 2024
Note: Screen patients for hepatitis B (HBV) prior to initiating therapy. In patients who have evidence of prior HBV infection, consult with providers with expertise in managing HBV before and/or during avacopan treatment.
Antineutrophil cytoplasmic autoantibody-associated vasculitis (adjunctive agent): Oral: 30 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary; has not been studied in patients on dialysis.
Note: Use is not recommended in patients with active, untreated, and/or uncontrolled chronic liver disease (eg, chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risks and benefits before use in patients with liver disease.
Baseline hepatic impairment:
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment during treatment:
AST or ALT >3 times ULN: Evaluate and consider interrupting treatment as clinically indicated.
AST or ALT >5 times ULN, or AST or ALT >3 times ULN and bilirubin >2 times ULN: Discontinue treatment until avacopan-induced liver injury is ruled out.
Hepatitis B virus reactivation: Discontinue treatment immediately. Resumption of avacopan in patients whose hepatitis B virus (HBV) reactivation resolves should be discussed with providers with expertise in managing HBV.
Hypersensitivity reactions : If angioedema occurs, discontinue avacopan immediately. Do not readminister avacopan unless another cause for angioedema has been established.
Serious infection: Interrupt treatment if a patient develops a serious or opportunistic infection. Therapy may be resumed once infection is controlled.
Refer to adult dosing.
Reactivation of hepatitis B virus (HBV), including life-threatening hepatitis B, has been reported with avacopan.
Risk factors:
• Prior hepatitis B infection
Hepatotoxicity, including abnormal hepatobiliary function and increased serum transaminases have commonly been reported with avacopan; severe hepatic disease has also been reported.
Risk factors:
• Liver disease
Avacopan may cause infection, including serious infection (eg, pneumonia, urinary tract infection).
Mechanism: Dose-related; related to the pharmacologic action of avacopan.
Risk factors:
• Chronic or recurrent infections
• History of serious or opportunistic infection
• Underlying conditions that may predispose to infection
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Hypertension (18%)
Dermatologic: Skin rash (11%)
Gastrointestinal: Diarrhea (15%), nausea (24%), vomiting (15%)
Hepatic: Hepatotoxicity (13%; including abnormal hepatobiliary function and increased serum transaminases; severe hepatoxicity: 5%) (table 1)
|
Drug (Avacopan) |
Comparator (Prednisone) |
Number of Patients (Avacopan) |
Number of Patients (Prednisone) |
Comments |
|---|---|---|---|---|
|
13% |
12% |
166 |
164 |
Including abnormal hepatobiliary function and increased serum transaminases |
|
Severe: 5% |
4% |
166 |
164 |
N/A |
Nervous system: Headache (21%)
1% to 10%:
Gastrointestinal: Upper abdominal pain (7%)
Genitourinary: Urinary tract infection (serious: 2%) (table 2)
|
Drug (Avacopan) |
Comparator (Prednisone) |
Number of Patients (Avacopan) |
Number of Patients (Prednisone) |
Comments |
|---|---|---|---|---|
|
2% |
1% |
166 |
164 |
Serious urinary tract infection |
Hypersensitivity: Angioedema (1%)
Nervous system: Dizziness (7%), fatigue (10%), paresthesia (5%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (4%)
Renal: Acute kidney injury (2%), increased serum creatinine (6%)
Respiratory: Pneumonia (5%) (table 3)
|
Drug (Avacopan) |
Comparator (Prednisone) |
Number of Patients (Avacopan) |
Number of Patients (Prednisone) |
|---|---|---|---|
|
5% |
4% |
166 |
164 |
Frequency not defined: Infection: Reactivation of HBV
Serious hypersensitivity to avacopan or any component of the formulation.
Concerns related to adverse effects:
• Hepatitis B virus reactivation: Hepatitis B virus (HBV) reactivation, including life-threatening hepatitis B, has been observed. In patients who have evidence of prior hepatitis B infection, consult with providers with expertise in managing HBV before and/or during avacopan treatment.
• Hepatotoxicity: Transaminase elevations and hepatobiliary events, including serious and life-threatening events, have been reported in patients taking avacopan.
• Hypersensitivity: Angioedema has been rarely reported in patients taking avacopan.
• Infections: Serious infections, including fatal infections, have occurred. Active serious infections should be resolved prior to avacopan use. Use with caution in patients with chronic or recurrent infections, prior exposure to tuberculosis, history of a serious or opportunistic infection, underlying conditions that may predispose them to infection, or those who have resided or traveled in areas of endemic tuberculosis or endemic mycoses.
Special populations:
• Hepatic impairment: Use is not recommended in patients with active, untreated, and/or uncontrolled chronic liver disease (eg, chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risks and benefits before use in patients with liver disease.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Tavneos: 10 mg [contains peg-40 hydrog castor oil(cremophor rh40)]
No
Capsules (Tavneos Oral)
10 mg (per each): $107.10
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.
Capsule, Oral:
Tavneos: 10 mg
Oral: Swallow capsule whole; do not crush, chew, or open. Administer with food.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Tavneos: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214487s000lbl.pdf#page=17
Antineutrophil cytoplasmic autoantibody-associated vasculitis: Adjunctive treatment of severe active antineutrophil cytoplasmic autoantibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) in combination with standard therapy, including glucocorticoids, in adults.
Avacopan may be confused with abacavir, argatroban.
Tavneos may be confused with Tymlos.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
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.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
CarBAMazepine: May decrease the serum concentration of Avacopan. Avacopan may increase the serum concentration of CarBAMazepine. Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Avacopan. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Avacopan. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Avacopan. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: Avacopan may increase the serum concentration of Lonafarnib. Lonafarnib may increase the serum concentration of Avacopan. Management: Avoid this combination if possible. If coadministration is required, use a lonafarnib dose of 115 mg/m2 and reduce the avacopan dose to 30 mg once daily. Monitor patients for lonafarnib and avacopan toxicities. Risk D: Consider therapy modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Administration with a high-fat, high-calorie meal increases AUC by 72% and Cmax by 8%.
Management: Administer with food.
Adverse events were observed in some animal reproduction studies.
Information related to the treatment of active antineutrophil cytoplasmic autoantibody associated vasculitis in pregnant patients is limited (Raza 2021; Singh 2018). Pregnant patients were not included in initial avacopan studies (Jayne 2021; Merkel 2020).
It is not known if avacopan is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Breastfeeding patients were not included in initial avacopan studies (Jayne 2021; Merkel 2020).
LFTs at baseline prior to initiating therapy, every 4 weeks for the first 6 months of therapy, and as clinically indicated thereafter; hepatitis B virus screening at baseline prior to initiating therapy; signs/symptoms of infection during and after treatment.
Avacopan is a complement 5a (C5a) receptor antagonist that inhibits the interaction between C5a receptor and the anaphylatoxin C5a. Avacopan blocks C5a-mediated neutrophil activation and migration.
Absorption: Coadministration with a high-fat, high-calorie meal increases AUC by ~72%.
Distribution: Vd: 345 L.
Protein binding: >99.9% to albumin and alpha-1-acid glycoprotein.
Metabolism: Hepatic via CYP3A4.
Half-life elimination: 97.6 hours.
Excretion: Feces: ~77% (7% as unchanged drug); urine: ~10% (<0.1% as unchanged drug).
Clearance: 16.3 L/hour.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
