Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Everolimus
laboratory: Novartis Europharm Ltd
Box of 3 blister packs of 10
All forms
Indication
Advanced breast cancer with positive hormone receptors
Afinitor is indicated for the treatment of advanced hormone receptor-positive breast cancer, HER2 / neu-negative, in combination with exemestane, in postmenopausal women without symptomatic visceral involvement following recurrence or progression of the disease and previously treated with a non-inhibitory inhibitor. -stheroidal aromatase.Neuroendocrine tumors of pancreatic origin
Afinitor is indicated for the treatment of unresectable or metastatic pancreatic neuroendocrine tumors that are well or moderately differentiated with progression of the disease in adults.Kidney cancer
Afinitor is indicated for the treatment of advanced kidney cancer in patients who have progressed under or after targeted anti-VEGF therapy.
Dosage AFINITOR 10 mg Tablet Box of 3 blister packs of 10
Afinitor treatment should be started and followed by a doctor experienced in cancer treatments.
Dosage
For different dosages Afinitor is available in 2.5 mg, 5 mg and 10 mg tablets.
The recommended dose of everolimus is 10 mg once daily. Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs. If a dose is missed, the patient should not take an extra dose, but take the next prescribed dose as usual. Dosage Adjustment for Adverse Events Management of serious and / or poorly tolerated adverse reactions suspected to be treatment-related may require dose reduction and / or temporary discontinuation of Afinitor therapy. For Grade 1 adverse events, dose adjustment is not usually necessary. If it is necessary to reduce the dosage, the recommended dose is 5 mg per day and should not be less than 5 mg per day.Table 1 summarizes the recommendations for dose adjustment for specific adverse events (see also Warnings and Precautions ).
Table 1 Recommendations for Dosage Adjustment of Afinitor
Undesirable effect | Severity 1 | Dosage adjustment of Afinitor | |
Noninfectious pneumonitis | Grade 2 | Consider interruption of treatment until improvement symptoms at Grade ≤ 1. Re-introduce the 5 mg daily treatment. Stop treatment in the absence of recovery in a 4 weeks delay. | |
Grade 3 | Discontinue treatment until symptom resolution at Grade ≤ 1. Consider resuming 5 mg daily. If Grade 3 toxicity reappears, consider stopping treatment. | ||
Grade 4 | Stop the treatment. | ||
stomatitis | Grade 2 | Interrupt the treatment temporarily until recovery to Grade ≤ 1. Re-introduce the treatment at the same dose. In case of recurrence of Grade 2 stomatitis, discontinue treatment until recovery to Grade ≤ 1. Re-introduce the 5 mg daily treatment. | |
Grade 3 | Discontinue treatment temporarily until recovery to Grade ≤ 1. Re-introduce treatment at 5 mg daily. | ||
Grade 4 | Stop the treatment. | ||
Other toxicities no hematologic (except metabolic events) | Grade 2 | If the toxicity is acceptable, no adaptation of the dosage is necessary. If the toxicity comes unacceptable, interrupt temporarily treatment until recovery at a Grade ≤ 1. Re-introduce the treatment at the same dose. If Grade 2 toxicity recurs, discontinue treatment until recovery to Grade ≤ 1. Re-introduce the 5 mg daily treatment. | |
Grade 3 | Temporarily abort treatment until recovery to Grade ≤ 1. Consider re-introducing the 5 mg daily regimen. Yes Grade 3 toxicity reappears, consider stopping treatment. | ||
Grade 4 | Stop the treatment. | ||
Metabolic events (by example hyperglycemia, dyslipidemia) | Grade 2 | No dosage adjustment is necessary. | |
Grade 3 | Abort the treatment temporarily. Re-introduce the 5 mg daily treatment. | ||
Grade 4 | Stop the treatment. | ||
thrombocytopenia | Grade 2 (<75, ≥ 50x10 9 / l) | Interrupt the treatment temporarily until recovery to Grade ≤ 1 (≥ 75x10 9 / l). Re-introduce the treatment at the same dose. | |
Grade 3 & 4 (<50x10 9 / l) | Interrupt the treatment temporarily until recovery to Grade ≤ 1 (≥ 75x10 9 / l). Re-introduce the treatment at 5 mg daily. | ||
neutropenia | Grade 2 (≥ 1x10 9 / l) | No dosage adjustment is necessary. | |
Grade 3 (<1, ≥ 0.5x10 9 / l) | Interrupt the treatment temporarily until r establishment at Grade ≤ 2 (≥ 1x10 9 / l). Re-introduce the treatment at the same dose. | ||
Grade 4 (<0.5x10 9 / l) | Interrupt the treatment temporarily until Recovery to Grade ≤ 2 (≥ 1x10 9 / l) Re - introduce treatment to 5 mg daily. | ||
neutropenia febrile | Grade 3 | Discontinue treatment temporarily until recovery to Grade ≤ 2 (≥ 1, 25x10 9 / l) and no fever. Re-introduce the 5 mg daily treatment. | |
Grade 4 | Stop the treatment. | ||
1 Grades evaluated according to the international classification scale CTCAE (Common Terminology Criteria for Adverse Events) v3.0 of the National Cancer Institute (NCI) | |||
Special population
Elderly patients (≥ 65 years old)
No dosage adjustment is necessary (see section 5.2 ).
Renal failure
No dosage adjustment is necessary (see section 5.2 ).
Hepatic insufficiency
• Mild hepatic impairment (Child-Pugh Class A) - the recommended daily dose is 7.5 mg.
• Moderate hepatic insufficiency (Child-Pugh class B) - the recommended daily dose is 5 mg.
• Severe hepatic insufficiency (Child-Pugh class C) - Afinitor is only recommended if the expected benefit outweighs the risk. In this case, the daily dose should not exceed 2.5 mg.
Dosage adjustment should be performed if the patient's hepatic function (Child-Pugh) changes during treatment (see also sections Warnings and Precautions for Use and Pharmacokinetic Properties ).
Pediatric population
The safety and effectiveness of Afinitor in children aged 0 to 18 years have not been established. No data available.
Administration mode
Afinitor should be taken orally once a day at the same time each day, with or without food steadily (see section Pharmacokinetic properties ). Afinitor tablets should be swallowed whole with a glass of water. The tablets should not be chewed or crushed.
Against indications
Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients listed under Composition .
Adverse effects Afinitor
Tolerance Profile Summary
The safety profile is derived from pooled data from 2, 406 Afinitor-treated patients in eight clinical studies, including four randomized, double-blind, placebo-controlled phase III studies and four phase II studies, based on approved indications. The most common adverse events (incidence ≥ 1/10) from pooled safety data were (in descending order): stomatitis, rash, fatigue, diarrhea, infections, nausea, decreased appetite, anemias, dysgeusia, pneumopathies, decreased weight, peripheral edema, asthenia, pruritus, epistaxis, hyperglycemia, hypercholesterolemia, headache and vomiting. The most common adverse reactions of Grades 3-4 (frequency ≥ 1/100 to <1/10) were: stomatitis, anemia, hyperglycemia, fatigue, infections, pneumonitis, diarrhea, asthenia, thrombocytopenia, neutropenia, dyspnea, proteinuria, lymphopenia, hypophosphatemia, rash and hypertension. Grades follow the CTCAE version 3.0 classification.List of adverse reactions in tabular form
Table 3 shows the adverse event frequency categories reported in the pooled analyzes taken into account for pooled tolerance. Adverse effects are presented according to MedDRA organ classes and frequency categories. Frequency categories are defined according to the following convention: very common (≥ 1/10); frequent (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10 000, <1/1000); very rare (<1 / 10, 000), not known (can not be stimulated based on available data). Within each frequency group, adverse effects should be presented in order of decreasing severity.Table 3 Adverse Reactions Reported in Clinical Studies
| Infections and infestations | |
Very common | Infections a, * |
| Blood and lymphatic system disorders | |
Very common | Anemia |
Frequent | Thrombocytopenia, neutropenia, leukopenia, lymphopenia |
Rare | pancytopenia |
Rare | Pure red cell aplasia |
| Immune system disorders | |
Rare | hypersensitivity |
| Metabolism and nutrition disorders | |
Very common | Decreased appetite, hyperglycemia, hypercholesterolemia |
Frequent | Hypertriglyceridaemia, hypophosphatemia, diabetes mellitus, hyperlipidemia, hypokalemia, dehydration, hypocalcemia |
| Psychiatric disorders | |
Frequent | Insomnia |
| Nervous system disorders | |
Very common | Dysgeusia, headache |
Rare | ageusia |
| Eye disorders | |
Frequent | Edema of the eyelid |
Rare | Conjunctivitis |
| Heart conditions | |
Rare | Congestive heart failure |
| Vascular disorders | |
Frequent | Hypertension, hemorrhage b |
Rare | Flushing vasomotor, deep vein thrombosis |
| Respiratory, thoracic and mediastinal disorders | |
Very common | Pneumopathy c, epistaxis |
Frequent | Cough dyspnea |
Rare | Hemoptysis, pulmonary embolism |
Rare | Acute Respiratory Distress Syndrome |
| Gastrointestinal disorders | |
Very common | Stomatitis, diarrhea, nausea, vomiting |
Frequent | Oral dryness, abdominal pain, mucositis, oral pain, dyspepsia, dysphagia |
| Hepatobiliary disorders | |
Frequent | Increased alanine aminotransferase, increased aspartate aminotransferase |
| Affections of the | skin and subcutaneous tissue |
Very common | Rash, itching |
Frequent | Skin dryness, nail alteration, mild alopecia, acne, erythema, onychoclasia, hand-foot syndrome, exfoliation, skin lesion |
Rare | Angioedema |
| Musculoskeletal and systemic disorders | |
Frequent | arthralgia |
| Renal and urinary disorders | |
Frequent | Proteinuria *, increased creatinine, renal failure * |
Rare | Increased diurnal urination, acute renal failure * |
| Disorders of reproductive organs and breast | |
Rare | Irregular menstruation |
Rare | Amenorrhea |
| General disorders and administration site conditions | |
Very common | Fatigue, peripheral edema, asthenia |
Frequent | pyrexia |
Rare | Non-cardiac chest pain |
Rare | Alteration of wound healing |
| investigations | |
Very common | Weightloss |
* See also the sub-section "Description of certain adverse effects" a Includes all effects of the organ class "infections and infestations" including (frequent) pneumonia and (infrequent) herpes zoster, sepsis and isolated cases of opportunistic infections [eg, aspergillosis, candidiasis and hepatitis B (see also section 4.4)] b Includes different haemorrhagic events not listed individually c Includes (frequent) pulmonary interstitial pneumonitis, pulmonary infiltration and (rare) pulmonary alveolar hemorrhage, pulmonary toxicity and alveolitis d Includes (very common) stomatitis, (common) canker sores, oral ulcer and tongue and (uncommon) glossod ynie, glossitis | |
Description of some adverse effects
In cases reported during clinical studies and spontaneously after marketing, everolimus has been associated with severe cases of reactivation of hepatitis B, including a case of fatal outcome. The reactivation of infections is an expected effect during the immunosuppression phases.In clinical studies and pharmacovigilance reports for spontaneous notification, everolimus has been associated with reports of renal failure (including fatal outcomes) and proteinuria. Monitoring of renal function is recommended (see section Warnings and precautions for use ).
In cases reported during clinical studies and spontaneously after marketing, everolimus has been associated with amenorrhea (secondary amenorrhea and other menstrual irregularities).The elderly
When pooling safety data, 36% of Afinitor-treated patients were 65 years of age or older. The number of patients with an adverse event that led to discontinuation was higher in patients 65 years and older (19% vs. 12%). The most common adverse events leading to discontinuation were pneumopathies, stomatitis, fatigue and dyspnoea.Reporting of suspected adverse reactions
The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system - see Annex V.
