Voydeya

/ Alexion

Treatment should be initiated by a healthcare professional experienced in the management of patients with haematological disorders.
The recommended starting dose is 150 mg three times a day administered orally, approximately 8 hours apart (± 2 hours). Dose can be increased to 200 mg three times a day after a minimum of 4 weeks of treatment depending on clinical response.
See prescribing information for full details.

Add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have residual haemolytic anaemia

* Hypersensitivity to the active substance or to any of the excipients.
* Patients with unresolved Neisseria meningitidis infection at treatment initiation.
* Patients who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination

General
Danicopan must not be administered as monotherapy as the efficacy has not been established. It should only be prescribed as an add-on to ravulizumab or eculizumab.
Serious infections
Serious infections caused by encapsulated bacteria
Patients receiving complement inhibitor therapy may have increased susceptibility to serious, lifet hreatening, or fatal infections caused by encapsulated bacteria including Neisseria meningitidis (caused by any serogroup, including non-groupable strains) and Streptococcus pneumoniae. Patients must be up to date on their vaccines against encapsulated bacteria, including Neisseria meningitidis and Streptococcus pneumoniae according to current national guidelines for vaccination use, prior to receiving the first dose of danicopan. The initiation of danicopan treatment is contraindicated in patients with unresolved serious infections caused by encapsulated bacteria.
Patients who initiate treatment less than 2 weeks after receiving a meningococcal and streptococcus vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients must be vaccinated against Neisseria meningitidis serogroups A, C, Y, and W135 to prevent the commonly pathogenic meningococcal serogroups. Vaccination against serogroup B, where available, is also recommended. Consideration should be given to official guidance on the appropriate use of antibacterial agents.
All patients treated with danicopan should be monitored for early signs of serious infection and sepsis, evaluated immediately if infection is suspected, and treated with appropriate antibiotics. Patients should be informed of these signs and symptoms and steps should be taken to seek medical care immediately.
Severe renal impairment
Patients with severe renal impairment that dose escalate to 150 mg three times a day should be monitored for adverse events during treatment with danicopan due to higher exposure expected in these patients.
Low body weight
Patients weighing < 60 kg should be monitored for adverse events during treatment with danicopan due to higher exposure expected in these patients.
Hepatic enzymes increase
Alanine aminotransferase (ALT) elevations have been observed in clinical trials . It is recommended that liver enzyme tests are performed before treatment begins. Following initiation of treatment, routine chemistry laboratory monitoring as per PNH management is recommended. Treatment interruption or discontinuation should be considered if elevations are clinically significant or if patients become symptomatic. Danicopan is not recommended in patients with severe hepatic impairment .
Discontinuation
At doses higher than 200 mg three times a day, ALT elevations occurred after treatment cessation without dose tapering in healthy subjects . Upon discontinuation, the dose should be tapered over 6 days.

Very common: Headache, Hepatic enzyme increased, Pyrexia
Common: Hypertension, Vomiting, Pain in extremity
See prescribing information for full details.

P-gp substrates: Co-administration of a single oral dose of 180 mg fexofenadine, a P-gp substrate, with 150 mg three times daily doses of danicopan resulted in increased fexofenadine Cmax and AUC0-inf by 1.42-fold and 1.62-fold, respectively. The results suggest that danicopan is a mild inhibitor of P-gp. Caution may be needed in co-administering medicinal products that are known to be substrates of P-gp (such as dabigatran, digoxin, edoxaban, fexofenadine, tacrolimus).
BCRP substrates: Co-administration of a single oral dose of 20 mg rosuvastatin, a BCRP substrate, with 200 mg three times daily doses of danicopan resulted in increased rosuvastatin Cmax and AUC0-inf by 3.29-fold and 2.25-fold, respectively. This result suggests that danicopan is an inhibitor of BCRP. Caution may be needed in co-administering medicinal products that are known to be substrates of BCRP (such as rosuvastatin and sulfasalazine).

Pregnancy: There are no data from the use of danicopan in pregnant women. As a precautionary measure, it is preferable to avoid the use during pregnancy.
Lactation: A risk to the newborns/infants cannot be excluded. Danicopan should not be used during breast-feeding and breast-feeding should not be initiated until 3 days after treatment discontinuation.

Single doses up to 1200 mg and multiple doses up to 800 mg twice a day have been taken in healthy volunteers. ALT elevations occurred after treatment cessation without a taper in 2 subjects who received 500 mg and 800 mg twice a day for 14 days. All abnormal ALT findings were transient, with no evidence of hepatic function abnormality and resolved spontaneously.
In case of overdose, elevations in aminotransferase and other liver parameters may occur. General supportive measures are recommended. It is not known whether danicopan can be removed by dialysis.