PubChem compound: 86278347
Ropeginterferon alfa-2b interacts in the following cases:
Co-administration of pegylated interferon alfa-2b modestly increased the exposure of caffeine (CYP1A2 substrate) and desipramine (CYP2D6 substrate).
Therefore, care should be taken when ropeginterferon alfa-2b is co-administered with CYP1A2 substrates notably those having a narrow therapeutic margin such as theophylline or methadone. Likewise, caution is recommended with CYP2D6 substrates (e.g., vortioxetine, risperidone) combined with ropeginterferon alfa-2b. Ropeginterferon alfa-2b may inhibit the activity of CYP1A2 and CYP2D6 and thus may increase the blood concentrations of these medicinal products.
A reduced starting dose for ropeginterferon alfa-2b of 50 micrograms is recommended for patients with severe (GFR 15-29 mL/min) renal impairment.
Caution must be exercised when administering ropeginterferon alfa-2b in combination with other potentially myelosuppressive/chemotherapeutic agents.
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with ropeginterferon alfa-2b.
Patients should have eye examinations before and during ropeginterferon alfa-2b therapy, specifically in those patients with retinopathy associated disease such as diabetes mellitus or hypertension.
Patients with pre-existing or a history of cardiovascular disorders should be closely monitored during ropeginterferon alfa-2b therapy.
There are no or limited amount of data from the use of interferon alfa in pregnant women.
Studies in animals have shown reproductive toxicity.
As ropeginterferon alfa-2b may have the same effect, it is not recommended during pregnancy and in women of childbearing potential not using contraception.
It is not known whether ropeginterferon alfa-2b is excreted in human 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 ropeginterferon alfa-2b therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Women of childbearing potential must use effective contraception during the treatment with ropeginterferon alfa-2b, unless otherwise discussed with the physician.
There are no data on the effect of ropeginterferon alfa-2b therapy on the fertility of females or males.
Ropeginterferon alfa-2b has minor influence on the ability to drive and use machines. Patients who experience dizziness, somnolence or hallucination during ropeginterferon alfa-2b therapy should avoid driving or using machines.
The most common adverse reactions are leukopenia (20.2%), thrombocytopenia (18.5%), arthralgia (13.5%), fatigue (12.4%), increased gamma-glutamyltransferase (11.2%), influenza-like illness (11.2%), myalgia (10.7%), anaemia (9.6%), increased alanine aminotransferase (8.4%), neutropenia (7.9%), pyrexia (7.9%), increased aspartate aminotransferase (7.3%), pruritus (6.8%), pain in extremity (6.7%), alopecia (6.7%), headache (6.2%), diarrhoea (5.7%), injection site reaction (5.6%), chills (5.1%), and dizziness (5.1%).
Serious adverse reactions are depression (1.1%), atrial fibrillation (1.1%) and acute stress disorder (0.6%).
Following treatment-related adverse reactions were reported with ropeginterferon alfa-2b in clinical studies in 178 polycythaemia vera adult patients. Adverse reactions are listed by system organ class and frequency (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), very rare (<1/10,000) or not known (cannot be estimated from available data).
| System organ class | Frequency | Adverse reaction |
|---|---|---|
| Infections and infestations | common | respiratory tract infection, influenza, rhinitis, fungal skin infection |
| uncommon | oral herpes, herpes zoster, oral candidiasis, sinusitis, oesophageal candidiasis, vulvovaginal mycotic infection, hordeolum, onychomycosis | |
| Blood and lymphatic system disorders | very common | leukopenia, thrombocytopenia |
| common | pancytopenia, neutropenia, anaemia | |
| Immune system disorders | uncommon | sarcoidosis |
| very rare | idiopathic or thrombotic thrombocytopenic purpura# | |
| not known | Vogt-Koyanagi-Harada disease#, acute hypersensitivity reactions#** | |
| Endocrine disorders | common | hypothyroidism, hyperthyroidism, thyroiditis |
| uncommon | Basedow’s disease, diabetes mellitus# | |
| Metabolism and nutrition disorders | common | hypertriglyceridaemia, decreased appetite |
| Psychiatric disorders | common | depression, aggression#, insomnia, anxiety, mood altered, mood swings, mood disorders |
| uncommon | suicide attempt#, suicidal ideation#, confusional state#, acute stress disorder, hallucination, emotional distress, nervousness nightmare, irritability | |
| rare | bipolar disorder#, mania# | |
| Nervous system disorders | common | headache, dizziness, hypoesthesia, somnolence, paraesthesia |
| uncommon | polyneuropathy, peripheral motor neuropathy, radiculopathy, migraine, mental impairment, tremor, aura | |
| Eye disorders | common | dry eye |
| uncommon | retinal haemorrhage#, retinal exudates#, visual impairment, visual acuity reduced, vision blurred, ocular discomfort, eczema eyelids | |
| rare | retinopathy#, optic neuropathy#, retinal artery occlusion#, retinal vein occlusion# | |
| very rare | blindness# | |
| not known | retinal detachment# | |
| Ear and labyrinth disorders | uncommon | deafness, tinnitus, vertigo |
| Cardiac disorders | common | atrial fibrillation |
| uncommon | myocardial infarction#, atrioventricular block, intracardiac thrombus, aortic valve incompetence, cardiovascular disorder | |
| rare | cardiomyopathy#, angina pectoris# | |
| very rare | myocardial ischemia# | |
| Vascular disorders | common | microangiopathy |
| uncommon | Raynaud’s phenomenon, hypertension, haematoma, flushing | |
| Respiratory, thoracic and mediastinal disorders | common | dyspnoea |
| uncommon | pneumonitis, cough, epistaxis, throat irritation | |
| very rare | lung infiltration# | |
| not known | pulmonary fibrosis#, pneumonia#, pulmonary arterial hypertension#* | |
| Gastrointestinal disorders | common | diarrhoea, nausea, abdominal pain, constipation, abdominal distension, dry mouth |
| uncommon | gastritis, abdominal wall disorder, flatulence, frequent bowel movements, odynophagia, gingival bleeding | |
| not known | tooth disorder#, periodontal disease# | |
| Hepatobiliary disorders | very common | gamma-glutamyltransferase increased |
| common | liver disorder, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased | |
| uncommon | hepatotoxicity, hepatitis toxic, hepatomegaly, porphyria non-acute | |
| rare | hepatic failure# | |
| Skin and subcutaneous tissue disorders | common | pruritus, alopecia, rash, erythema, psoriasis, xeroderma, dermatitis acneiform, hyperkeratosis, hyperhidrosis, dry skin |
| uncommon | photosensitivity reaction, skin exfoliation, nail dystrophy | |
| not known | skin depigmentation# | |
| Musculoskeletal and connective tissue disorders | very common | arthralgia, myalgia |
| common | Sjogren’s syndrome, arthritis, pain in extremity, musculoskeletal pain, bone pain, muscle spasms | |
| uncommon | muscular weakness, neck pain, groin pain | |
| Renal and urinary disorders | uncommon | cystitis haemorrhagic, dysuria, micturition urgency, urinary retention |
| Reproductive system and breast disorders | uncommon | erectile dysfunction, haematospermia |
| General disorders and administration site conditions | very common | influenza-like illness, fatigue |
| common | pyrexia, injection site reaction, asthenia, chills, general physical health deterioration, injection site erythema | |
| uncommon | injection site pain, injection site pruritus, sensitivity to weather change | |
| not known | tongue hyperpigmentation# | |
| Investigations | common | antithyroid antibody positive, blood thyroid stimulating hormone increased, body temperature increased, antinuclear antibody positive, blood lactate dehydrogenase increased, weight decreased |
| uncommon | platelet count increased, blood uric acid increased, Coombs test positive |
# Reported as adverse reactions during treatment with other interferon alfa medicinal products.
* Class label for interferon medicinal products, see below pulmonary arterial hypertension.
** e.g., urticaria, angioedema, bronchoconstriction, or anaphylaxis.
The most common adverse reactions (including number of patients, incidence rate, severity grade, necessity for dose adaptation and outcome) reported during the ropeginterferon alfa-2b clinical development program are summarised in the following table.
Most common adverse reactions during ropeginterferon alfa-2b treatment:
| ADR >10% PT | N (%) N=178 | IR | CTCAE intensity grade ≥3 N (%) | Dose reduced N (%) | Medicinal Product interrupted N (%) | Medicinal Product discontinued N (%) | Recovered N (%) |
|---|---|---|---|---|---|---|---|
| Leukopenia | 36 (20.2%) | 21.2 | 3 (8.3) | 5 (13.9) | 4 (11.1) | n.r. | 8 (22.2) |
| Thrombocytopenia | 33 (18.5%) | 11.2 | 4 (12.1) | 3 (9.1) | 2 (6.1) | n.r. | 6 (18.2) |
| Arthralgia | 24 (13.5%) | 5.2 | 1 (4.2) | 4 (16.7) | 3 (12.5) | 1 (4.2) | 15 (62.5) |
| Fatigue | 22 (12.4%) | 6.6 | n.r. | 3 (13.6) | 1 (4.5) | 1 (4.5) | 11 (50.0) |
| Gamma-glutamyl- transferase increased | 20 (11.2%) | 7.9 | 7 (35.0) | 3 (15.0) | n.r. | n.r. | 4 (20.0) |
| Influenza like illness | 20 (11.2%) | 4.9 | n.r. | 4 (20.0) | 2 (10.0) | n.r. | 10 (50.0) |
| Myalgia | 19 (10.7%) | 3.5 | n.r. | 2 (10.5) | 1 (5.3) | n.r. | 9 (47.4) |
No CTCAE grade 5 (death) adverse reactions reported for these preferred terms; 1 AE grade 4 (life-threating or disabling) reported for Gamma-glutamyltransferase increased.
Abbreviations: CTCAE, common terminology criteria for adverse events; n.r., not reported; ADR, adverse drug reaction; PT, preferred term; IR, incidence rate of mean adverse events per 100 patients per year; N, number of patients.
N (%) number and percentage of patients with given AE
Gastrointestinal disorders have been reported with other interferon alfa medicinal products and have been reported in 15.7% of patients with ropeginterferon alfa-2b treatment. The most common gastrointestinal disorders reported in these studies were diarrhoea (5.1%; incidence rate: 2.8 [events/100 patients per year]) and nausea (4.5%; incidence rate: 1.2 events/100 patients per year]).
In the clinical development program of ropeginterferon alfa-2b, two cases of serious depression (1.1%; incidence rate: 0.4 events/100 patients per year) occurred. The patients recovered completely after permanent medicinal product discontinuation. One patient who experienced serious acute stress disorder (0.6%; incidence rate: 0.2 events/100 patients per year) with moderate intensity recovered completely after the dose of ropeginterferon alfa-2b was reduced. CNS effects including suicide attempt, suicidal ideation, aggression, bipolar disorder, mania and confusion have been reported with interferon alfa.
During ropeginterferon alfa-2b therapy, three cases of atrial fibrillation (1.1%; incidence rate: 0.3 events/100 patients per year) with intensity grade 1 to 3 occurred in two patients. Ropeginterferon alfa-2b treatment was continued, and the patients received appropriate medicinal products to treat these events. Patients recovered from the two events; one event was ongoing at the time of assessment.
Cases of pulmonary arterial hypertension (PAH) have been reported with interferon alfa, notably in patients with risk factors for PAH (such as portal hypertension, HIV infection, cirrhosis). Events were reported at various time points typically several months after starting treatment with interferon alfa.
Serious eye disorders have been reported with interferon alfa such as retinopathy, retinal haemorrhage, retinal exudates, retinal detachment and retinal artery or vein occlusion.
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