Drugs List

Therapeutic Indications

Uses

Granulomatosis with polyangiitis
Microscopic polyangiitis

Treatment of severe, active granulomatosis with polyangiitis or microscopic polyangiitis in adult patients, in combination with a rituximab or cyclophosphamide regimen.

Contraindications

Children under 18 years
Lymphocyte count below 0.5 x 10 to the power 9/L at baseline
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
White cell count below 3.5 x 10 to the power 9/L at baseline
Breastfeeding
Pregnancy
Serum bilirubin above 3 times upper limit of normal
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

History of hepatitis B
History of hepatitis C
History of tuberculosis
Positive HIV status
Renal impairment - eGFR below 15ml/minute/1.73m sq
Small-vessel vasculitis with alveolar haemorrhage

Administration of live vaccines is not recommended
Before starting therapy ensure immunisations are up to date
Pneumocystis jiroveci pneumonia (PCP) prophylaxis if treating GPA and MPA
Treatment to be initiated and supervised by a specialist
Contains macrogolglycerol hydroxystearate
Contains polysorbate
Blood counts should be performed before and periodically during treatment
Monitor transaminases & total bilirubin before initiation and as indicated
Perform white blood cell count before initiation and as indicated
Monitor for Neisseria infections as per standard practice
Monitor patient for signs of serious infection
Advise patient to report immediately any symptoms of angioedema
Advise patient to report immediately signs/symptoms bone marrow suppression
Advise patient to report symptoms of infection immediately
Immunosuppressive drugs may increase risk of malignancy
Discontinue if ALT/AST > 3x ULN & signs of hepatotoxicity
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if AST or ALT level > 3x ULN and INR > 1.5
Discontinue if AST or ALT level exceeds 5x ULN for more than 2 weeks
Discontinue if AST or ALT level exceeds 8 x ULN
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Interrupt therapy if neutrophil count <1.0x10 to the power 9/L
Interrupt treatment if angioedema due to hypersensitivity occurs
Interrupt treatment if severe infection develops
Suspend treatment if AST/ALT is 3-5 times upper limit of normal
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment

Before and during treatment, patients must notify their physician if they have been diagnosed with tuberculosis, HIV infection, hepatitis B or hepatitis C.

Patients treated for ANCA-associated vasculitis must be monitored according to standard practise for clinical signs and symptoms of Neisseria infections.

It is recommended that patients receiving avacopan treatment also receive pneumocystis pneumonia prophylaxis.

Administration of live viral vaccines is not recommended and should only be administered before treatment initiation, or during quiescent phase of the disease.

Use with caution in patients taking low-bioavailability P-gp substrates as the excipient macrogolglycerol hydroxystearate may affect plasma levels of some P-gp substrates. See product literature.

Pregnancy and Lactation

Pregnancy

Avacopan is contraindicated during pregnancy.

The manufacturer does not recommend using avacopan during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Avacopan is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues avacopan or discontinues breastfeeding. Animal data reports levels of avacopan in breast milk however the presence in human breast milk is unknown. Effects on exposed infants are unknown.

Side Effects

Abnormal liver function
Alanine aminotransferase increased
Angioedema
Bronchitis
Candidiasis (mouth or throat)
Cardiac disorders
Cellulitis
Creatine phosphokinase increased
Diarrhoea
Gamma glutamyl transferase (GGT) increased
Gastro-enteritis
Headache
Herpes zoster
Increase of liver transaminases
Influenza
Leucopenia
Lower respiratory tract infection
Nasopharyngitis
Nausea
Neutropenia
Oral herpes
Otitis media
Pneumonia
Rhinitis
Serum bilirubin increased
Sinusitis
Upper abdominal pain
Upper respiratory tract infection
Urinary tract infections
Vomiting
White blood cell count decreased

Presentation

Oral formulations of avacopan.

Drugs List

Therapeutic Indications

Uses

Granulomatosis with polyangiitis
Microscopic polyangiitis

Treatment of severe, active granulomatosis with polyangiitis or microscopic polyangiitis in adult patients, in combination with a rituximab or cyclophosphamide regimen.

Dosage

30mg twice daily, morning and evening with food.

Avacopan should be administered in combination with rituximab or cyclophosphamide regimen as below:
Rituximab for 4 weekly intravenous doses and glucocorticoids as clinically necessary
OR
Oral or intravenous cyclophosphamide for 13 or 14 weeks, followed by oral azathioprine or mycophenolate mofetil and glucocorticoids as clinically necessary

Additional Dosage Information

Contraindications

Children under 18 years
Lymphocyte count below 0.5 x 10 to the power 9/L at baseline
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
White cell count below 3.5 x 10 to the power 9/L at baseline
Breastfeeding
Pregnancy
Serum bilirubin above 3 times upper limit of normal
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

History of hepatitis B
History of hepatitis C
History of tuberculosis
Positive HIV status
Renal impairment - eGFR below 15ml/minute/1.73m sq
Small-vessel vasculitis with alveolar haemorrhage

Administration of live vaccines is not recommended
Before starting therapy ensure immunisations are up to date
Pneumocystis jiroveci pneumonia (PCP) prophylaxis if treating GPA and MPA
Treatment to be initiated and supervised by a specialist
Contains macrogolglycerol hydroxystearate
Contains polysorbate
Blood counts should be performed before and periodically during treatment
Monitor transaminases & total bilirubin before initiation and as indicated
Perform white blood cell count before initiation and as indicated
Monitor for Neisseria infections as per standard practice
Monitor patient for signs of serious infection
Advise patient to report immediately any symptoms of angioedema
Advise patient to report immediately signs/symptoms bone marrow suppression
Advise patient to report symptoms of infection immediately
Immunosuppressive drugs may increase risk of malignancy
Discontinue if ALT/AST > 3x ULN & signs of hepatotoxicity
Discontinue if AST or ALT level > 3x ULN and bilirubin > 2x ULN
Discontinue if AST or ALT level > 3x ULN and INR > 1.5
Discontinue if AST or ALT level exceeds 5x ULN for more than 2 weeks
Discontinue if AST or ALT level exceeds 8 x ULN
Interrupt therapy if lymphocyte count less than 0.2 x10 to the power of 9/L
Interrupt therapy if neutrophil count <1.0x10 to the power 9/L
Interrupt treatment if angioedema due to hypersensitivity occurs
Interrupt treatment if severe infection develops
Suspend treatment if AST/ALT is 3-5 times upper limit of normal
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Ensure adequate contraception during treatment

Before and during treatment, patients must notify their physician if they have been diagnosed with tuberculosis, HIV infection, hepatitis B or hepatitis C.

Patients treated for ANCA-associated vasculitis must be monitored according to standard practise for clinical signs and symptoms of Neisseria infections.

It is recommended that patients receiving avacopan treatment also receive pneumocystis pneumonia prophylaxis.

Administration of live viral vaccines is not recommended and should only be administered before treatment initiation, or during quiescent phase of the disease.

Use with caution in patients taking low-bioavailability P-gp substrates as the excipient macrogolglycerol hydroxystearate may affect plasma levels of some P-gp substrates. See product literature.

Pregnancy and Lactation

Pregnancy

Avacopan is contraindicated during pregnancy.

The manufacturer does not recommend using avacopan during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Avacopan is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues avacopan or discontinues breastfeeding. Animal data reports levels of avacopan in breast milk however the presence in human breast milk is unknown. Effects on exposed infants are unknown.

Side Effects

Abnormal liver function
Alanine aminotransferase increased
Angioedema
Bronchitis
Candidiasis (mouth or throat)
Cardiac disorders
Cellulitis
Creatine phosphokinase increased
Diarrhoea
Gamma glutamyl transferase (GGT) increased
Gastro-enteritis
Headache
Herpes zoster
Increase of liver transaminases
Influenza
Leucopenia
Lower respiratory tract infection
Nasopharyngitis
Nausea
Neutropenia
Oral herpes
Otitis media
Pneumonia
Rhinitis
Serum bilirubin increased
Sinusitis
Upper abdominal pain
Upper respiratory tract infection
Urinary tract infections
Vomiting
White blood cell count decreased

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2022

Reference Sources

Summary of Product Characteristics: Tavneos (Avacopan). Vifor Fresenius Medical Care Renal Pharma UK Ltd. Revised May 2022.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 December 2022