Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Accord Healthcare S.L.U., World Trade Center, Moll de Barcelona, s/n, Edifici Est 6ª planta, 08039 Barcelona, Spain
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Lactation (see section 4.6).
Patients who have baseline neutrophil counts < 1,500 cells/mm³.
Naveruclif is an albumin-bound nanoparticle formulation of paclitaxel, which may have substantially different pharmacological properties compared to other formulations of paclitaxel (see sections 5.1 and 5.2). It should not be substituted for or with other paclitaxel formulations.
Rare occurrences of severe hypersensitivity reactions, including very rare events of anaphylactic reactions with fatal outcome, have been reported. If a hypersensitivity reaction occurs, the medicinal product should be discontinued immediately, symptomatic treatment should be initiated, and the patient should not be rechallenged with paclitaxel.
Bone marrow suppression (primarily neutropenia) occurs frequently with human serum albumin-paclitaxel nanoparticles. Neutropenia is dose-dependent and a dose-limiting toxicity. Frequent monitoring of blood cell counts should be performed during Naveruclif therapy. Patients should not be retreated with subsequent cycles of Naveruclif until neutrophils recover to >1500 cells/mm³ and platelets recover to >100,000 cells/mm³ (see section 4.2).
Sensory neuropathy occurs frequently with human serum albumin-paclitaxel nanoparticles, although development of severe symptoms is less common. The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose reduction. When Naveruclif is used as monotherapy, if Grade 3 sensory neuropathy develops, treatment should be withheld until resolution to Grade 1 or 2 followed by a dose reduction for all subsequent courses of Naveruclif is recommended (see section 4.2). For combination use of Naveruclif and gemcitabine, if Grade 3 or higher peripheral neuropathy develops, withhold Naveruclif; continue treatment with gemcitabine at the same dose. Resume Naveruclif at reduced dose when peripheral neuropathy improves to Grade 0 or 1 (see section 4.2). For combination use of Naveruclif and carboplatin, if Grade 3 or higher peripheral neuropathy develops, treatment should be withheld until improvement to Grade 0 or 1 followed by a dose reduction for all subsequent courses of Naveruclif and carboplatin (see section 4.2).
Sepsis was reported at a rate of 5% in patients with or without neutropenia who received human serum albumin-paclitaxel nanoparticles in combination with gemcitabine. Complications due to the underlying pancreatic cancer, especially biliary obstruction or presence of biliary stent, were identified as significant contributing factors. If a patient becomes febrile (regardless of neutrophil count), initiate treatment with broad spectrum antibiotics. For febrile neutropenia, withhold Naveruclif and gemcitabine until fever resolves and ANC ≥ 1,500 cells/mm³, then resume treatment at reduced dose levels (see section 4.2).
Pneumonitis occurred in 1% of patients when human serum albumin-paclitaxel nanoparticles was used as monotherapy and in 4% of patients when human serum albumin-paclitaxel nanoparticles were used in combination with gemcitabine. Closely monitor all patients for signs and symptoms of pneumonitis. After ruling out infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue treatment with Naveruclif and gemcitabine and promptly initiate appropriate treatment and supportive measures (see section 4.2).
Because the toxicity of paclitaxel can be increased with hepatic impairment, administration of Naveruclif in patients with hepatic impairment should be performed with caution. Patients with hepatic impairment may be at increased risk of toxicity, particularly from myelosuppression; such patients should be closely monitored for development of profound myelosuppression.
Naveruclif is not recommended in patients that have total bilirubin > 5 x ULN or AST > 10 x ULN. In addition, Naveruclif is not recommended in patients with metastatic adenocarcinoma of the pancreas that have moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and AST ≤ 10 x ULN) (see section 5.2).
Rare reports of congestive heart failure and left ventricular dysfunction have been observed among individuals receiving human serum albumin-paclitaxel nanoparticles. Most of the individuals were previously exposed to cardiotoxic medicinal products such as anthracyclines or had underlying cardiac history. Thus, patients receiving Naveruclif should be vigilantly monitored by physicians for the occurrence of cardiac events.
The effectiveness and safety of human serum albumin-paclitaxel nanoparticles in patients with central nervous system (CNS) metastases has not been established. CNS metastases are generally not well controlled by systemic chemotherapy.
If patients experience nausea, vomiting and diarrhoea following the administration of Naveruclif, they may be treated with commonly used anti-emetics and constipating agents.
Cystoid macular oedema (CMO) has been reported in patients treated with human serum albumin-paclitaxel nanoparticles. Patients with impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is diagnosed, Naveruclif treatment should be discontinued and appropriate treatment initiated (see section 4.8).
For patients of 75 years and older, no benefit for the combination treatment of human serum albumin-paclitaxel nanoparticles and gemcitabine in comparison to gemcitabine monotherapy has been demonstrated. In the very elderly (≥ 75 years) who received human serum albumin-paclitaxel nanoparticles and gemcitabine, there was a higher incidence of serious adverse reactions and adverse reactions that led to treatment discontinuation including haematologic toxicities, peripheral neuropathy, decreased appetite and dehydration. Patients with pancreatic adenocarcinoma aged 75 years and older should be carefully assessed for their ability to tolerate Naveruclif in combination with gemcitabine with special consideration to performance status, co-morbidities and increased risk of infections (see section 4.2 and 4.8).
Although limited data is available, no clear benefit in terms of prolonged overall survival has been demonstrated in pancreatic adenocarcinoma patients with normal CA 19-9 levels prior to start of treatment with human serum albumin-paclitaxel nanoparticles and gemcitabine (see section 5.1).
Erlotinib should not be co-administered with Naveruclif plus gemcitabine (see section 4.5).
This medicine contains less than 1 mmol sodium (23 mg) per 100 mg, that is to say essentially 'sodium free'
The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4 (see section 5.2). Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.
Paclitaxel and gemcitabine do not share a common metabolic pathway. Paclitaxel clearance is primarily determined by CYP2C8 and CYP3A4 mediated metabolism followed by biliary excretion, while gemcitabine is inactivated by cytidine deaminase followed by urinary excretion. Pharmacokinetic interactions between Naveruclif and gemcitabine have not been evaluated in humans.
A pharmacokinetic study was conducted with human serum albumin-paclitaxel nanoparticles and carboplatin in non-small cell lung cancer patients. There were no clinically relevant pharmacokinetic interactions between human serum albumin-paclitaxel nanoparticles and carboplatin.
Naveruclif is indicated as monotherapy for breast cancer, in combination with gemcitabine for pancreatic adenocarcinoma, or in combination with carboplatin for non-small cell lung cancer (see section 4.1).
Naveruclif should not be used in combination with other anticancer agents.
Interaction studies have only been performed in adults.
Women of childbearing potential should use effective contraception during treatment and up to 1 month after receiving treatment with Naveruclif. Male patients treated with Naveruclif are advised to use effective contraception and to avoid fathering a child during and up to six months after treatment.
There are very limited data on the use of paclitaxel in human pregnancy. Paclitaxel is suspected to cause serious birth defects when administered during pregnancy. Studies in animals have shown reproductive toxicity (see section 5.3). Women of childbearing potential should have a pregnancy test prior to starting treatment with Naveruclif. Naveruclif should not be used in pregnancy, and in women of childbearing potential not using effective contraception, unless the clinical condition of the mother requires treatment with paclitaxel.
Paclitaxel and/or its metabolites were excreted into the milk of lactating rats (see section 5.3). It is not known if paclitaxel is excreted in human milk. Because of potential serious adverse reactions in breast-feeding infants, Naveruclif is contraindicated during lactation. Breast-feeding must be discontinued for the duration of therapy.
Human serum albumin-paclitaxel nanoparticles induced infertility in male rats (see section 5.3). Based on findings in animals, male and female fertility may be compromised. Male patients should seek advice on conservation of sperm prior to treatment because of the possibility of irreversible infertility due to therapy with Naveruclif.
Paclitaxel has minor or moderate influence on the ability to drive and use machines. Paclitaxel may cause adverse reactions such as tiredness (very common) and dizziness (common) that may affect the ability to drive and use machinery. Patients should be advised not to drive and use machines if they feel tired or dizzy.
The most common clinically significant adverse reactions associated with the use of human serum albumin-paclitaxel nanoparticles have been neutropenia, peripheral neuropathy, arthralgia/myalgia and gastrointestinal disorders.
Table 6 lists adverse reactions associated with human serum albumin-paclitaxel nanoparticles monotherapy at any dose in any indication during clinical trials (N = 789), human serum albuminpaclitaxel nanoparticles in combination with gemcitabine for pancreatic adenocarcinoma from the phase III clinical trial (N = 421), human serum albumin-paclitaxel nanoparticles in combination with carboplatin for non-small cell lung cancer from the phase III clinical trial (N = 514) and from post-marketing use.
Frequencies are defined as: 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), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 6. Adverse reactions reported with human serum albumin-paclitaxel nanoparticles:
| Monotherapy (N=789) | Combination therapy with gemcitabine (N=421) | Combination therapy with carboplatin (N=514) | |
|---|---|---|---|
| Infections and infestations | |||
| Common: | Infection, urinary tract infection, folliculitis, upper respiratory tract infection, candidiasis, sinusitis | Sepsis, pneumonia, oral candidiasis | Pneumonia, bronchitis, upper respiratory tract infection, urinary tract infection |
| Uncommon: | Sepsis1, neutropenic sepsis1, pneumonia, oral candidiasis, nasopharyngitis, cellulitis, herpes simplex, viral infection, herpes zoster, fungal infection, catheter-related infection, injection site infection | Sepsis, oral candidiasis | |
| Neoplasms benign, malignant and unspecified (including cysts and polyps) | |||
| Uncommon: | Tumour necrosis, metastatic pain | ||
| Blood and lymphatic system disorders | |||
| Very common: | Bone marrow suppression, neutropenia, thrombocytopenia, anaemia, leukopenia, lymphopenia | Neutropenia, thrombocytopenia, anaemia | Neutropenia3, thrombocytopenia3, anaemia3, leukopenia3 |
| Common: | Febrile neutropenia | Pancytopenia | Febrile neutropenia, lymphopenia |
| Uncommon: | Thrombotic thrombocytopenic purpura | Pancytopenia | |
| Rare: | Pancytopenia | ||
| Immune system disorders | |||
| Uncommon: | Hypersensitivity | Drug hypersensitivity, hypersensitivity | |
| Rare: | Severe hypersensitivity1 | ||
| Metabolism and nutrition disorders | |||
| Very common: | Anorexia | Dehydration, decreased appetite, hypokalaemia | Decreased appetite |
| Common: | Dehydration, decreased appetite, hypokalaemia | Dehydration | |
| Uncommon: | Hypophosphataemia, fluid retention, hypoalbuminaemia, polydipsia, hyperglycaemia, hypocalcaemia, hypoglycaemia, hyponatraemia | ||
| Not known: | Tumour lysis syndrome1 | ||
| Psychiatric disorders | |||
| Very common: | Depression, insomnia | ||
| Common: | Depression, insomnia, anxiety | Anxiety | |
| Uncommon: | Restlessness | Insomnia | |
| Nervous system disorders | |||
| Very common: | Peripheral neuropathy, neuropathy, hypoaesthesia, paraesthesia | Peripheral neuropathy, dizziness, headache, dysgeusia | Peripheral neuropathy |
| Common: | Peripheral sensory neuropathy, dizziness, peripheral motor neuropathy, ataxia, headache, sensory disturbance, somnolence, dysgeusia | Dizziness, headache, dysgeusia | |
| Uncommon: | Polyneuropathy, areflexia, syncope, postural dizziness, dyskinesia, hyporeflexia, neuralgia, neuropathic pain, tremor, sensory loss | VIIth nerve paralysis | |
| Not known: | Cranial nerve palsies multiple1 | ||
| Eye disorders | |||
| Common: | Vision blurred, lacrimation increased, dry eye, keratoconjunctivitis sicca, madarosis | Lacrimation increased | Vision blurred |
| Uncommon: | Reduced visual acuity, abnormal vision, eye irritation, eye pain, conjunctivitis, visual disturbance, eye pruritus, keratitis | Cystoid macular oedema | |
| Rare: | Cystoid macular oedema1 | ||
| Ear and labyrinth disorders | |||
| Common: | Vertigo | ||
| Uncommon: | Tinnitus, ear pain | ||
| Cardiac disorders | |||
| Common: | Arrhythmia, tachycardia, supraventricular tachycardia | Cardiac failure congestive, tachycardia | |
| Rare: | Cardiac arrest, cardiac failure congestive, left ventricular dysfunction, atrioventricular block1, bradycardia | ||
| Vascular disorders | |||
| Common: | Hypertension, lymphoedema, flushing, hot flushes | Hypotension, hypertension | Hypotension, hypertension |
| Uncommon: | Hypotension, orthostatic hypotension, peripheral coldness | Flushing | Flushing |
| Rare: | Thrombosis | ||
| Respiratory, thoracic and mediastinal disorders | |||
| Very common: | Dyspnoea, epistaxis, cough | Dyspnoea | |
| Common: | Interstitial pneumonitis2, dyspnoea, epistaxis, pharyngolaryngeal pain, cough, rhinitis, rhinorrhoea | Pneumonitis, nasal congestion | Haemoptysis, epistaxis, cough |
| Uncommon: | Pulmonary emboli, pulmonary thromboembolism, pleural effusion, exertional dyspnoea, sinus congestion, decreased breath sounds, productive cough, allergic rhinitis, hoarseness, nasal congestion, nasal dryness, wheezing | Dry throat, nasal dryness | Pneumonitis |
| Not known: | Vocal cord paresis1 | ||
| Gastrointestinal disorders | |||
| Very common: | Diarrhoea, vomiting, nausea, constipation, stomatitis | Diarrhoea, vomiting, nausea, constipation, abdominal pain, abdominal pain upper | Diarrhoea, vomiting, nausea, constipation |
| Common: | Gastrooesophageal reflux disease, dyspepsia, abdominal pain, abdominal distension, abdominal pain upper, oral hypoaesthesia | Intestinal obstruction, colitis, stomatitis, dry mouth | Stomatitis, dyspepsia, dysphagia, abdominal pain |
| Uncommon: | Rectal haemorrhage, dysphagia, flatulence, glossodynia, dry mouth, gingival pain, loose stools, oesophagitis, abdominal pain lower, mouth ulceration, oral pain | ||
| Hepatobiliary disorders | |||
| Common: | Cholangitis | Hyperbilirubinaemia | |
| Uncommon: | Hepatomegaly | ||
| Skin and subcutaneous tissue disorders | |||
| Very common: | Alopecia, rash | Alopecia, rash | Alopecia, rash |
| Common: | Pruritus, dry skin, nail disorder, erythema, nail pigmentation/discolouration, skin hyperpigmentation, onycholysis, nail changes | Pruritus, dry skin, nail disorder | Pruritus, nail disorder |
| Uncommon: | Photosensitivity reaction, urticaria, skin pain, generalised pruritus, pruritic rash, skin disorder, pigmentation disorder, hyperhidrosis, onychomadesis, erythematous rash, generalised rash, dermatitis, night sweats, maculo-papular rash, vitiligo, hypotrichosis, nail bed tenderness, nail discomfort, macular rash, papular rash, skin lesion, swollen face | Skin exfoliation, dermatitis allergic, urticaria | |
| Very rare: | Stevens-Johnson syndrome1, toxic epidermal necrolysis1 | ||
| Not known: | Palmar-plantar erythrodysaesthesiae syndrome1,4, scleroderma1 | ||
| Musculoskeletal and connective tissue disorders | |||
| Very common: | Arthralgia, myalgia | Arthralgia, myalgia, pain in extremity | Arthralgia, myalgia |
| Common: | Back pain, pain in extremity, bone pain, muscle cramps, limb pain | Muscular weakness, bone pain | Back pain, pain in extremity, musculoskeletal pain |
| Uncommon: | Chest wall pain, muscular weakness, neck pain, groin pain, muscle spasms, musculoskeletal pain, flank pain, limb discomfort, muscle weakness | ||
| Renal and urinary disorders | |||
| Common: | Acute renal failure | ||
| Uncommon: | Haematuria, dysuria, pollakiuria, nocturia, polyuria, urinary incontinence | Haemolytic uraemic syndrome | |
| Reproductive system and breast disorders | |||
| Uncommon: | Breast pain | ||
| General disorders and administration site conditions | |||
| Very common: | Fatigue, asthenia, pyrexia | Fatigue, asthenia, pyrexia, oedema peripheral, chills | Fatigue, asthenia, oedema peripheral |
| Common: | Malaise, lethargy, weakness, peripheral oedema, mucosal inflammation, pain, rigors, oedema, decreased performance status, chest pain, influenza-like illness, hyperpyrexia | Infusion site reaction | Pyrexia, chest pain |
| Uncommon: | Chest discomfort, abnormal gait, swelling, injection site reaction | Mucosal inflammation, infusion site extravasation, infusion site inflammation, infusion site rash | |
| Rare: | Extravasation | ||
| Investigations | |||
| Very common: | Weight decreased, alanine aminotransferase increased | ||
| Common: | Decreased weight, increased alanine aminotransferase, increased aspartate aminotransferase, decreased haematocrit, decreased red blood cell count, increased body temperature, increased gammaglutamyltransferase, increased blood alkaline phosphatase | Aspartate aminotransferase increased, blood bilirubin increased, blood creatinine increased | Weight decreased, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased |
| Uncommon: | Increased blood pressure, increased weight, increased blood lactate dehydrogenase, increased blood creatinine, increased blood glucose, increased blood phosphorus, decreased blood potassium, increased bilirubin | ||
| Injury, poisoning and procedural complications | |||
| Uncommon: | Contusion | ||
| Rare: | Radiation recall phenomenon, radiation pneumonitis | ||
1 As reported in the post-marketing surveillance of human serum albumin-paclitaxel nanoparticles.
2 The frequency of pneumonitis is calculated based on pooled data in 1,310 patients in clinical trials receiving human serum albumin-paclitaxel nanoparticles monotherapy for breast cancer and for other indications.
3 Based on laboratory assessments: maximal degree of myelosuppression (treated population).
4 In some patients previously exposed to capecitabine.
This section contains the most common and clinically relevant adverse reactions related to human serum albumin-paclitaxel nanoparticles injection.
Adverse reactions were assessed in 229 patients with metastatic breast cancer who were treated with 260 mg/m² human serum albumin-paclitaxel nanoparticles once every three weeks in the pivotal phase III clinical study (human serum albumin-paclitaxel nanoparticles monotherapy).
Adverse reactions were assessed in 421 patients with metastatic pancreatic cancer who were treated with serum albumin-paclitaxel nanoparticles in combination with gemcitabine (125 mg/m² human serum albumin-paclitaxel nanoparticles in combination with gemcitabine at a dose of 1000 mg/m² given on Days 1, 8 and 15 of each 28-day cycle) and 402 gemcitabine monotherapy-treated patients receiving first-line systemic treatment for metastatic adenocarcinoma of the pancreas(human serum albumin-paclitaxel nanoparticles /gemcitabine).
Adverse reactions were assessed in 514 patients with non-small cell lung cancer who were treated with human serum albumin-paclitaxel nanoparticles in combination with carboplatin (100 mg/m² human serum albumin-paclitaxel nanoparticles given on Days 1, 8 and 15 of each 21-day cycle in combination with carboplatin given on Day 1 of each cycle) in the phase III randomized, controlled clinical trial (human serum albumin-paclitaxel nanoparticles/carboplatin). Patient-reported taxane toxicity was assessed using the 4 subscales of the Functional Assessment of Cancer Therapy (FACT)-Taxane questionnaire. Using repeated measure analysis, 3 of the 4 subscales (peripheral neuropathy, pain hands/feet and hearing) favoured human serum albumin-paclitaxel nanoparticles and carboplatin (p ≤ 0.002). For the other subscale (oedema), there was no difference in the treatment arms.
Sepsis was reported at a rate of 5% in patients with or without neutropenia who received human serum albumin-paclitaxel nanoparticles in combination with gemcitabine during the conduct of a trial in pancreatic adenocarcinoma. Of the 22 cases of sepsis reported in patients treated with human serum albumin-paclitaxel nanoparticles in combination with gemcitabine, 5 had a fatal outcome. Complications due to the underlying pancreatic cancer, especially biliary obstruction or presence of biliary stent, were identified as significant contributing factors. If a patient becomes febrile (regardless of neutrophil count), initiate treatment with broad spectrum antibiotics. For febrile neutropenia, withhold Naveruclif and gemcitabine until fever resolves and ANC ≥ 1,500 cells/mm³, then resume treatment at reduced dose levels (see section 4.2).
In patients with metastatic breast cancer, neutropenia was the most notable important haematological toxicity (reported in 79% of patients) and was rapidly reversible and dose-dependent; leukopenia was reported in 71% of patients. Grade 4 neutropenia (< 500 cells/mm³) occurred in 9% of patients treated with human serum albumin-paclitaxel nanoparticles. Febrile neutropenia occurred in four patients on human serum albumin-paclitaxel nanoparticles. Anaemia (Hb < 10 g/dl) was observed in 46% of patients on human serum albumin-paclitaxel nanoparticles and was severe (Hb < 8 g/dl) in three cases. Lymphopenia was observed in 45% of the patients.
Table 7 provides the frequency and severity of haematologic laboratory-detected abnormalities for patients treated with human serum albumin-paclitaxel nanoparticles in combination with gemcitabine or with gemcitabine.
Table 7. Haematologic laboratory-detected abnormalities in pancreatic adenocarcinoma trial:
| Human serum albumin-paclitaxel nanoparticles (125 mg/m²)/Gemcitabine | Gemcitabine | |||
|---|---|---|---|---|
| Grades 1-4 (%) | Grade 3-4 (%) | Grades 1-4 (%) | Grade 3-4 (%) | |
| Anaemiaa,b | 97 | 13 | 96 | 12 |
| Neutropeniaa,b | 73 | 38 | 58 | 27 |
| Thrombocytopeniab,c | 74 | 13 | 70 | 9 |
a 405 patients assessed in human serum albumin-paclitaxel nanoparticles/gemcitabine-treated group
b 388 patients assessed in gemcitabine-treated group
c 404 patients assessed in human serum albumin-paclitaxel nanoparticles/gemcitabine-treated group
Anaemia and thrombocytopenia were more commonly reported in the human serum albumin-paclitaxel nanoparticles and carboplatin arm than in the Taxol and carboplatin arm (54% versus 28% and 45% versus 27% respectively).
In general, the frequency and severity of neurotoxicity was dose-dependent in patients receiving human serum albumin-paclitaxel nanoparticles. Peripheral neuropathy (mostly Grade 1 or 2 sensory neuropathy) was observed in 68% of patients on human serum albumin-paclitaxel nanoparticles with 10% being Grade 3, and no cases of Grade 4.
For patients treated with human serum albumin-paclitaxel nanoparticles in combination with gemcitabine, the median time to first occurrence of Grade 3 peripheral neuropathy was 140 days. The median time to improvement by at least 1 grade was 21 days, and the median time to improvement from Grade 3 peripheral neuropathy to Grade 0 or 1 was 29 days. Of the patients with treatment interrupted due to peripheral neuropathy, 44% (31/70 patients) were able to resume human serum albuminpaclitaxel nanoparticles at a reduced dose. No patients treated with human serum albumin-paclitaxel nanoparticles in combination with gemcitabine had Grade 4 peripheral neuropathy.
For non-small cell lung cancer patients treated with human serum albumin-paclitaxel nanoparticles and carboplatin, the median time to first occurrence of Grade 3 treatment-related peripheral neuropathy was 121 days, and the median time to improvement from Grade 3 treatment related peripheral neuropathy to Grade 1 was 38 days. No patients treated with human serum albumin-paclitaxel nanoparticles and carboplatin experienced Grade 4 peripheral neuropathy.
There have been rare reports during post-marketing surveillance of reduced visual acuity due to cystoid macular oedema during treatment with human serum albumin-paclitaxel nanoparticles (see section 4.4).
Pneumonitis has been reported at a rate of 4% with the use of human serum albumin-paclitaxel nanoparticles in combination with gemcitabine. Of the 17 cases of pneumonitis reported in patients treated with human serum albumin-paclitaxel nanoparticles in combination with gemcitabine, 2 had a fatal outcome. Monitor patients closely for signs and symptoms of pneumonitis. After ruling out infectious aetiology and upon making a diagnosis of pneumonitis, permanently discontinue treatment with Naveruclif and gemcitabine and promptly initiate appropriate treatment and supportive measures (see section 4.2).
Human serum albumin-paclitaxel nanoparticles monotherapy-metastatic breast cancer Nausea occurred in 29% of the patients and diarrhoea in 25% of the patients.
Alopecia was observed in >80% of the patients treated with human serum albumin-paclitaxel nanoparticles. The majority of alopecia events occurred less than one month after initiation of human serum albumin-paclitaxel nanoparticles. Pronounced hair loss ≥ 50% is expected for the majority of patients who experience alopecia.
Arthralgia occurred in 32% of patients on human serum albumin-paclitaxel nanoparticles and was severe in 6% of cases. Myalgia occurred in 24% of patients on human serum albumin-paclitaxel nanoparticles and was severe in 7% of cases. The symptoms were usually transient, typically occurred three days after human serum albumin-paclitaxel nanoparticles administration and resolved within a week.
Asthenia/Fatigue was reported in 40% of the patients.
The study consisted of 106 patients, 104 of whom were paediatric patients aged from 6 months to less than 18 years (see section 5.1). Every patient experienced at least 1 adverse reaction. The most frequently reported adverse reactions were neutropenia, anaemia, leukopenia and pyrexia. Serious adverse reactions reported in more than 2 patients were pyrexia, back pain, peripheral oedema and vomiting. No new safety signals were identified in the limited number of paediatric patients treated with human serum albumin-paclitaxel nanoparticles and the safety profile was similar to that of the adult population.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
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