Chemical formula: C₂₇H₄₅N₅O₅ Molecular mass: 519.677 g/mol PubChem compound: 10324367
Boceprevir interacts in the following cases:
The data available warrant caution in patients at risk of QT prolongation (long congenital QT, hypokalaemia).
Caution should be exercised with medicines known to prolong QT interval such as amiodarone, quinidine, methadone, pentamidine and some neuroleptics.
Boceprevir in combination with ribavirin and peginterferon alfa is contraindicated in women who are pregnant.
No effects on foetal development have been observed in rats and rabbits. There are no data on the use of boceprevir in pregnant women.
Due to the combined treatment with peginterferon alfa and ribavirin, extreme care must be taken to avoid pregnancy in female patients or in female partners of male patients. Therefore, female patients of childbearing potential must use an effective contraceptive during treatment and for 4 months after treatment has been concluded. Male patients or their female partners must use an effective contraceptive during treatment and for 7 months after treatment has been concluded.
Refer to Summary of Product Characteristics for ribavirin and peginterferon alfa for additional information.
Boceprevir/metabolites are excreted in rat milk. It is not known whether boceprevir is excreted in human breast milk. A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy with boceprevir taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
No human data on the effect of boceprevir on fertility are available. Effects on fertility and Sertoli cells have been observed in rats but not in mice and monkeys. Clinical data (semen analyses and inhibin B levels – [a glycoprotein produced by Sertoli cells – used as a surrogate marker of testicular function]) showed no evidence of altered testicular function. Available pharmacodynamic/toxicological data in rats have shown effects of boceprevir/metabolites on fertility, which in females have been shown to be reversible.
Combination therapy of boceprevir, peginterferon alfa and ribavirin may influence some patients' ability to drive and use machines. Patients should be informed that fatigue, dizziness, syncope, blood pressure fluctuations and blurred vision have been reported.
The safety profile represented by approximately 1,500 patients for the combination of boceprevir with peginterferon alfa-2b and ribavirin was based on pooled safety data in two clinical trials: one in patients who were previously untreated, and one in patients who had failed prior therapy.
The most frequently reported adverse reactions were fatigue, anaemia, nausea, headache, and dysgeusia.
The most common reason for dose reduction was anaemia, which occurred more frequently in subjects receiving the combination of boceprevir with peginterferon alfa-2b and ribavirin than in subjects receiving peginterferon alfa-2b and ribavirin alone.
Adverse reactions are listed by System Organ Class. Within each system organ class, adverse reactions are listed under headings of frequency using the categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known (cannot be estimated from the available data).
Adverse reactions in combination with boceprevir with peginterferon alfa-2b and ribavirin reported during clinical trials † and ‡:
Common: Bronchitis*, cellulitis*, herpes simplex, influenza, oral fungal infection, sinusitis
Uncommon: Gastroenteritis*, pneumonia*, staphylococcal infection*, candidiasis, ear infection, fungal skin infection, nasopharyngitis, onychomycosis, pharyngitis, respiratory tract infection, rhinitis, skin infection, urinary tract infection
Rare: Epiglottitis*, otitis media, sepsis
Rare: Thyroid neoplasm (nodules)
Very common: Anaemia*, neutropenia*
Common: Leukopenia*, thrombocytopenia*, pancytopenia, agranulocytosis
Uncommon: Haemorrhagic diathesis, lymphadenopathy, lymphopenia
Rare: Haemolysis
Rare: Sarcoidosis*, porphyria non-acute
Common: Goitre, hypothyroidism
Uncommon: Hyperthyroidism
Very common: Decreased appetite*
Common: Dehydration*, hyperglycaemia*, hypertriglyceridaemia, hyperuricaemia
Uncommon: Hypokalaemia* ̧ appetite disorder, diabetes mellitus, gout, hypercalcaemia
Very common: Anxiety*, depression*, insomnia, irritability
__Common: Affect lability, agitation, libido disorder, mood altered, sleep disorder
Uncommon: Aggression*, homicidal ideation*, panic attack*, paranoia*, substance abuse*, suicidal ideation*, abnormal behaviour, anger, apathy, confusional state, mental status changes, restlessness
Rare: Bipolar disorder*, completed suicide*, suicide attempt*, hallucination auditory, hallucination visual, psychiatric decompensation
Very common: Dizziness*, headache*
Common: Hypoaesthesia*, paraesthesia*, syncope*, amnesia, disturbance in attention, memory impairment, migraine, parosmia, tremour, vertigo
Uncommon: Neuropathy peripheral*, cognitive disorder, hyperaesthesia, lethargy, loss of consciousness, mental impairment, neuralgia, presyncope
Rare: Cerebral ischaemia*, encephalopathy
Common: Dry eye, retinal exudates, vision blurred, visual impairment
Uncommon: Retinal ischaemia*, retinopathy*, abnormal sensation in eye, conjunctival haemorrhage, conjunctivitis, eye pain, eye pruritus, eye swelling, eyelid oedema, lacrimation increased, ocular hyperaemia, photophobia
Rare: Papilloedema
Common: Tinnitus
Uncommon: Deafness*, ear discomfort, hearing impaired
Common: Palpitations
Uncommon: Tachycardia*, arrhythmia, cardiovascular disorder
Rare: Acute myocardial infarction*, atrial fibrillation*, coronary artery disease*, pericarditis*, pericardial effusion
Common: Hypotension*, hypertension
Uncommon: Deep vein thrombosis*, flushing, pallor, peripheral coldness
Rare: Venous thrombosis
Very common: Cough*, dyspnoea*
Common: Epistaxis, nasal congestion, oropharyngeal pain, respiratory tract congestion, sinus congestion, wheezing
Uncommon: Pleuritic pain*, pulmonary embolism*, dry throat, dysphonia, increased upper airway secretion, oropharyngeal blistering
Rare: Pleural fibrosis*, orthopnoea, respiratory failure
Very common: Diarrhoea*, nausea*, vomiting* dry mouth, dysgeusia
Common: Abdominal pain*, abdominal pain upper*, constipation*, gastrooesophageal reflux disease*, haemorrhoids*, abdominal discomfort, abdominal distention, anorectal discomfort, aphthous stomatitis, cheilitis, dyspepsia, flatulence, glossodynia, mouth ulceration, oral pain, stomatitis, tooth disorder
Uncommon: Abdominal pain lower*, gastritis*, pancreatitis*, anal pruritus, colitis, dysphagia, faeces discoloured, frequent bowl movements, gingival bleeding, gingival pain, gingivitis, glossitis, lip dry, odynophagia, proctalgia, rectal haemorrhage, salivary hypersecretion, sensitivity of teeth, tongue discolouration, tongue ulceration
Rare: Pancreatic insufficiency
Uncommon: Hyperbilirubinaemia
Rare: Cholecystitis*
Very common: Alopecia, dry skin, pruritus, rash
Common: Dermatitis, eczema, erythema, hyperhidrosis, night sweats, oedema peripheral, psoriasis, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, skin lesion
Uncommon: Photosensitivity reaction, skin ulcer, urticaria
Not known: Angioedema, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome
Very common: Arthralgia, myalgia
Common: Back pain*, pain in extremity*, muscle spasms, muscular weakness, neck pain
Uncommon: Musculoskeletal chest pain*, arthritis, bone pain, joint swelling, musculoskeletal pain
Common: Pollakiuria
Uncommon: Dysuria, nocturia
Not known: Renal impairment
Common: Erectile dysfunction
Uncommon: Amenorrhoea, menorrhagia, metrorrhagia
Rare: Aspermia
Very common: Asthenia*, chills, fatigue*, pyrexia*, influenza-like illness
Common: Chest discomfort*, chest pain*, malaise*, feeling of body temperature change, mucosal dryness, pain
Uncommon: Feeling abnormal, impaired healing, non-cardiac chest pain
Very common: Weight decreased
Uncommon: Cardiac murmur, heart rate increased
Not known: Glomerular filtration rate decreased
* Includes adverse reactions which may be serious as assessed by the investigator in clinical trial subjects.
† Since boceprevir is prescribed with peginterferon alfa and ribavirin, please also refer to the respective Summary of Product Characteristics of peginterferon alfa and ribavirin.
‡ Injection-site reactions have not been included since boceprevir is administered orally.
Anaemia was observed in 49% of subjects treated with the combination of boceprevir with peginterferon alfa-2b and ribavirin compared with 29% of subjects treated with peginterferon alfa-2b and ribavirin alone. Boceprevir was associated with an additional decrease of approximately 1 g/dL in haemoglobin concentration. The mean decreases in haemoglobin values from baseline were larger in previously treated patients compared to patients who had never received prior therapy. Dose modifications due to anaemia/haemolytic anaemia occurred twice as often in patients treated with the combination of boceprevir with peginterferon alfa-2b and ribavirin (26%) compared to peginterferon alfa-2b and ribavirin alone (13%). In clinical trials, the proportion of subjects who received erythropoietin for the management of anaemia was 43% (667/1,548) of subjects in the boceprevir-containing arms compared to 24% (131/547) of subjects receiving peginterferon alfa-2b and ribavirin alone. The majority of the anaemia subjects received erythropoietin when haemoglobin levels were ≤10 g/dL (or 6.2 mmol/L). The proportion of subjects who received a transfusion for the management of anaemia was 3% of subjects in the boceprevir-containing arms compared to <1% of subjects receiving peginterferon alfa-2b and ribavirin alone.
The proportion of subjects with decreased neutrophils was higher in the boceprevir-containing arms compared to subjects receiving only peginterferon alfa-2b and ribavirin. The percentage of patients with Grades 3-4 neutropenia (neutrophil counts <0.75 × 109/L) was higher in boceprevir-treated patients (29%) than in placebo-treated patients (17%), in combination with peginterferon alfa-2b and ribavirin. Seven percent of subjects receiving the combination of boceprevir with peginterferon alfa-2b and ribavirin had neutrophil counts of <0.5 × 109/L (Grade 4 neutropenia) compared to 4% of subjects receiving only peginterferon alfa-2b and ribavirin.
Platelet counts were decreased for subjects in the boceprevir containing-arms (3%) compared to subjects receiving peginterferon alfa-2b and ribavirin alone (1%). In both treatment arms, patients with cirrhosis were at a higher risk to experience Grade 3-4 thrombocytopenia compared with non cirrhotic patients.
The addition of boceprevir to peginterferon alfa–2b and ribavirin was associated to higher incidences of increase in uric acid, triglycerides and cholesterol total compared to peginterferon alfa–2b and ribavirin only.
The safety profile of boceprevir in HCV/HIV-1 co-infected patients (n=64) was overall similar to the safety profile in mono-infected HCV patients.
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