Aldesleukin interacts in the following cases:
Concomitantly administered glucocorticoids may decrease the activity of aldesleukin and therefore should be avoided. However, patients who develop life-threatening signs or symptoms may be treated with dexamethasone until toxicity resolves to an acceptable level.
Antihypertensive agents, such as beta-blockers, may potentiate the hypotension seen with aldesleukin and therefore blood pressure should be monitored.
Antihypertensive agents, such as beta-blockers, may potentiate the hypotension seen with aldesleukin and therefore blood pressure should be monitored.
Aldesleukin may affect central nervous function. Therefore, interactions could occur following concomitant administration of centrally acting medicinal products. Aldesleukin may alter patient response to psychotropic medicinal products and therefore patients should be monitored.
Aldesleukin may affect central nervous function. Therefore, interactions could occur following concomitant administration of centrally acting medicinal products. Aldesleukin may alter patient response to psychotropic medicinal products and therefore patients should be monitored.
Use of contrast media after aldesleukin administration may result in a recall of the toxicity observed during aldesleukin administration. Most events were reported to occur within 2 weeks after the last dose of aldesleukin, but some occurred months later. Therefore it is recommended not to use contrast media within 2 weeks after treatment with aldesleukin.
Hypersensitivity reactions have been reported in patients receiving combination regimens containing sequential high dose aldesleukin and antineoplastic agents, specifically, dacarbazine, cis-platinum, tamoxifen and interferon-alpha. These reactions consisted of erythema, pruritus, and hypotension and occurred within hours of administration of chemotherapy. These events required medical intervention in some patients.
Severe rhabdomyolysis and myocardial injury, including myocardial infarction, myocarditis and ventricular hypokinesia appear to be increased in patients receiving aldesleukin (intravenously) and interferon-alpha concurrently.
There has also been exacerbation or the initial presentation of a number of autoimmune and inflammatory disorders observed following concurrent use of interferon-alpha and aldesleukin, including crescentic immunoglobulin A (IgA) glomerulonephritis, oculo-bulbar myasthenia gravis, inflammatory arthritis, thyroiditis, bullous pemphigoid, and Stevens-Johnson syndrome. It is recommended that patients with pre-existing auto-immune disease should not be treated with aldesleukin.
There are no adequate data on the use of aldesleukin in pregnant women.
Experimental animal studies are insufficient to assess the safety with respect to reproduction, development of the embryo or foetus, the course of gestation and peri- and postnatal development. Aldesleukin has been shown to have embryolethal and maternal toxic effects in rats.
The potential risk for humans is unknown.
Aldesleukin should not be used during pregnancy unless the potential benefit to the patient justifies the potential risk to the foetus.
It is not known whether this drug is excreted in human milk. Because the potential for serious adverse reactions in nursing infants is unknown, mothers should not breast feed their infants during treatment.
Both sexually active men and women should use effective methods of contraception during treatment.
Aldesleukin may affect central nervous system function. Hallucination, somnolence, syncope, convulsions may occur during treatment with aldesleukin and may affect the patient’s ability to drive and operate machines.
Patients should not drive or operate machines until they have recovered from the adverse drug reactions.
Frequency and severity of adverse reactions to aldesleukin have generally been shown to be dependent on route of administration, dose and schedule.
Most adverse reactions are self-limited and might reverse within 1 to 2 days of discontinuation of therapy. The rate of treatment-related deaths in the 255 metastatic RCC patients who received single-agent aldesleukin was 4% (11/255). In patients on subcutaneous treatment less than 1% died of treatment related adverse reactions.
Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: 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).
The following adverse drug reactions were reported from clinical studies and from post-marketing experience with aldesleukin:
Common: Respiratory tract infection, sepsis.
Very common: Anaemia, thrombocytopenia.
Common: Leucopenia, coagulopathy including disseminated intravascular coagulation, eosinophilia.
Uncommon: Neutropenia.
Rare: Agranulocytosis, aplastic anaemia, haemolytic anaemia, neutropenic fever.
Uncommon: Hypersensitivity reactions.
Rare: Anaphylaxis.
Very common: Hypothyroidism.
Common: Hyperthyroidism.
Very common: Anorexia.
Common: Acidosis, hyperglycaemia, hypocalcaemia, hypercalcaemia, hyperkalaemia, dehydration, hyponatraemia, hypophosphatemia.
Uncommon: Hypoglycaemia.
Rare: Diabetes mellitus.
Very common: Anxiety, confusion, depression, insomnia.
Common: Irritability, agitation, hallucinations.
Very common: Dizziness, headache, paraesthesia, somnolence.
Common: Neuropathy, syncope, speech disorders, taste loss, lethargy.
Uncommon: Coma, convulsions, paralysis, myasthenia.
Not known: Intracranial/cerebral haemorrhage, cerebrovascular accident, leukoencephalopathy (see additional information below).
Common: Conjunctivitis.
Rare: Optic nerve disorder including optic neuritis.
Very common: Tachycardia, arrhythmia, chest pain.
Common: Cyanosis, transient ECG changes, myocardial ischaemia, palpitations, cardiovascular disorders including cardiac failure.
Uncommon: Myocarditis, cardiomyopathy, cardiac arrest, pericardial effusion.
Rare: Ventricular hypokinesia.
Not known: Cardiac tamponade.
Very common: Hypotension.
Common: Phlebitis, hypertension.
Uncommon: Thrombosis, thrombophlebitis, haemorrhage.
Very common: Dyspnoea, cough.
Common: Pulmonary oedema, pleural effusions, hypoxia, haemoptysis, epistaxis, nasal congestion, rhinitis.
Rare: Pulmonary embolism, adult respiratory distress syndrome.
Very common: Nausea with or without vomiting, diarrhea, stomatitis.
Common: Dysphagia, dyspepsia, constipation, gastrointestinal bleeding including rectal haemorrhage, haematemesis, ascitis, cheilitis, gastritis.
Uncommon: Pancreatitis, intestinal obstruction, gastrointestinal perforation including necrosis/gangrene.
Rare: Activation of quiescent Crohn’s disease.
Common: Elevation of hepatic transaminases, elevation of alkaline phosphatase, elevation of lactic dehydrogenase, hyperbilirubinaemia, hepatomegaly or hepatosplenomegaly.
Rare: Cholecystitis, liver failure with fatal outcome.
Very common: Erythema and rash, exfoliative dermatitis, pruritus, sweating.
Common: Alopecia, urticaria.
Uncommon: Vitiligo, Quincke’s oedema.
Rare: Vesiculobullous rash, Stevens-Johnson syndrome.
Common: Myalgia, arthralgia.
Uncommon: Myopathy, myositis.
Not known: Rhabdomyolysis.
Very common: Oliguria, serum urea increased, serum creatinine increased.
Common: Haematuria, renal failure, anuria.
Very common: Injection site reaction*, injection site pain*, injection site inflammation*, fever with or without chills, malaise asthenia and fatigue, pain, oedema, weight gain, weight loss.
Common: Mucositis, injection site nodule, hypothermia, influenza like illness.
Rare: Injection site necrosis.
Notes:
* Frequency of injection site reaction, pain and inflammation is less following administration by continuous intravenous infusion.
There have been rare reports of leukoencephalopathy associated with aldesleukin in the literature, mostly in patients treated for HIV infection. In some cases there were other risk factors like opportunistic infections, co-administration of interferons as well as multiple courses of chemotherapy that might predispose the treated population to such event.
Cardiac arrhythmias (supraventricular and ventricular), angina pectoris, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, oedema and mental status changes may be associated with capillary leak syndrome. The frequency and severity of capillary leak syndrome are lower after subcutaneous administration than with continuous intravenous infusion.
During treatment most patients experience lymphocytopenia and eosinophilia with a rebound lymphocytosis within 24 to 48 hours following treatment. These may be related to the mechanism of antitumour activity of aldesleukin. Severe manifestations of eosinophilia have been reported, involving eosinophilic infiltration of cardiac and pulmonary tissues.
Cerebral vasculitis, both isolated and in combination with other manifestations, has been reported. Cutaneous and leukocytoplastic hypersensitivity vasculitis has been reported. Some of these cases are responsive to corticosteroids.
The following undesirable effects have been reported rarely in association with concurrent interferon alpha treatment: crescentic IgA glomerulonephritis, oculo-bulbar myasthenia gravis, inflammatory arthritis, thyroiditis, bullous pemphigoid and Stevens-Johnson syndrome. Severe rhabdomyolysis and myocardial injury, including myocardial infarction, myocarditis and ventricular hypokinesia appear to be increased in patients receiving aldesleukin (intravenously) and interferon-alpha concurrently.
Bacterial infection or exacerbation of bacterial infection, including septicaemia, bacterial endocarditis, septic thrombophlebitis, peritonitis, pneumonia, and local catheter site infection have been reported mainly after intravenous administration.
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