The most frequent manifestation of the side effect of interferons is the flu-like syndrome. It manifests itself in the form of weakness, fatigue, muscle pain, fever, chills, headache, nausea.These symptoms are usually more pronounced at the beginning of treatment, their frequency decreases as the treatment continues. Titration of the dose (treatment starts with 1/4 dose, increasing it by 1/4 every week) at the beginning of treatment helps to reduce the severity of the flu-like syndrome and its manifestations.
In any period of treatment, neurologic symptoms may appear that simulate exacerbation of multiple sclerosis: transient episodes of muscle hypertonicity and / or muscle weakness that hamper arbitrary movements. These episodes are limited in duration, related to the time of injection and may be repeated in subsequent administrations. In some cases, these neurological manifestations are accompanied by influenza-like symptoms.
The frequency of unwanted drug reactions is expressed in terms of patient-years of therapy, with the following categories.
Frequency unknown: (based on the available data, evaluation is not possible) The term "patient-year" is the sum of individual units of time,during which the patient participating in the study received Avonex® before developing an adverse reaction. For example, for a period of 100 patient-years, 100 patients treated for 1 year, or 200 patients who received treatment for 6 months, could be monitored.
Laboratory and instrumental research:
Often: lymphocytopenia, leukopenia, neutropenia, decreased hematocrit, increased potassium in the blood, increased blood urea nitrogen.
Infrequently: thrombocytopenia.
Frequency unknown: decrease in body weight, increase in body weight, deviation of the parameters of the functional liver test from normal.
Heart Disease:
Frequency unknown: cardiomyopathy, chronic heart failure, palpitations, arrhythmia, tachycardia.
Violations from the blood and lymphatic system:
Frequency unknown: pancytopenia, thrombocytopenia.
Infrequently: Thrombotic microangiopathy, incl. thrombotic thrombocytopenic
purpura / hemolytic uremic syndrome.
Impaired nervous system:
Often: headache.
Often: spasticity, hypoesthesia
Frequency unknown: neurologic symptoms, fainting3, hypertension,
dizziness, paresthesia, seizures, migraines.
Disturbances from the respiratory organs:
Often: rhinorrhea.
Rarely: shortness of breath.
Gastrointestinal disorders:
Often: vomiting, diarrhea, nausea2.
Disturbances from the skin and subcutaneous tissue:
Often: rash, intense sweating, signs of damage to the skin and subcutaneous tissue. Infrequently: alopecia.
Frequency unknown: angioedema, itching, vesicular rash, hives, exacerbation of psoriasis.
Disturbances from the skeletal-muscular and connective tissue:
Often: Muscular spasms, neck pain, myalgia2, arthalgia, pain in the extremities, pain in the
back, muscle stiffness, musculoskeletal rigidity.
Frequency unknown: systemic lupus erythematosus, muscle weakness, arthritis.
Disorders from the urinary system:
Infrequently: nephrotic syndrome, glomerulosclerosis.
Endocrine disorders:
Frequency unknown: hyperthyroidism, hypothyroidism.
Metabolic and nutritional disorders:
Often: anorexia.
Vascular disorders:
Often: "tides" of blood to the face.
Frequency unknown: vasodilation.
General disorders and disorders at the injection site:
Often: influenza-like symptoms, fever2, chills2, sweating2.
Often: pain at the injection site, erythema at the injection site, hematoma at the injection site, asthenia2,
pain, fatigue2, malaise, night sweats.
Infrequently: burning at the injection site.
Frequency unknown: reaction at the injection site, inflammation at the injection site, phlegmon at the injection site1, necrosis at the injection site, bleeding at the injection site, chest pain, abscess at the injection site1.
Immune system disorders:
Frequency unknown: anaphylactic reaction, anaphylactic shock, hypersensitivity reaction (angioedema, dyspnea, urticaria, rash, itching rash).
Hepatobiliary disorders:
Frequency unknown: hepatic failure, hepatitis, autoimmune hepatitis.
Disorders from the reproductive system and breast:
Infrequently: metrorrhagia, menorrhagia.
Mental disorders:
Often: depression, insomnia.
Frequency unknown: suicide, psychosis, anxiety, confusion, emotional lability.
1 The described reactions at the injection site include pain, inflammation and very rare cases of abscess or phlegmon that may require surgery.
2At the beginning of treatment, the frequency of these side effects may be higher.
3 After the injection of Avonex®, syncope is possible, as a rule, such fainting turns out to be the only episode at the beginning of treatment and is not repeated with subsequent injections.
Precautionary measures:
Avonex®, like other interferons, should be used with caution in patients with a history of, or presently, signs of a depressive disorder, especially with previous episodes of suicidal intent. It is known that depression and suicidal thinking occur in patients PC more often than in the population as a whole, and can be associated with the use of interferons. The occurrence of depressive states is possible at any time with Avonex®. If there are any signs of depression or suicidal thoughts, patients should immediately consult a doctor. Such patients should be carefully monitored during treatment and, if necessary, urgently applied appropriate treatment measures.In some cases, it may be necessary to stop the use of the drug.
Caution should be exercised when administering Avonex® to patients who have previously suffered seizures and who also take antiepileptic drugs, in particular if epilepsy treatment and the use of antiepileptic drugs are not monitored or monitored inadequately.
For interferon beta preparations, thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), including death, was noted. These phenomena were observed at various time points, from several weeks to several years from the start of interferon beta treatment. Early clinical manifestations included thrombocytopenia, increased blood pressure, fever, symptomatology from the central nervous system (including paresis, confusion), as well as kidney failure. Laboratory data on TMA include a decrease in the number of platelets, an increase in serum lactate dehydrogenase (LDH) due to hemolysis or schizocytosis (red blood cell fragmentation) in the blood smear.
Thus, if clinical signs of TMA are observed, monitoring of platelet count, serum LDH, blood smear and renal function is recommended.
With diagnosed TMA, immediate intervention (transfusion of blood plasma) and withdrawal of Avonex® are recommended.
During the treatment with interferon beta preparations, cases of nephropathy, which were based on focal segmental glomerulosclerosis (FSGS), lipid nephrosis (JIII), membranoproliferative glomerulonephritis (MPGH) and mnbranose glomerulopathy (IHP). These phenomena were observed at different time points and could occur within a few years from the beginning of treatment. Recommended periodic monitoring of early signs of the disease, such as proteinuria or decreased renal function, especially in patients with an increased risk of kidney damage. Upon detection, the therapy for nephrotic syndrome is immediately started and the drug Avonex® is canceled.
Care should be taken when prescribing the drug, as well as careful monitoring of patients with severe renal and hepatic insufficiency, and with oppression of bone marrow hematopoiesis.
With the use of interferon beta, the appearance of signs of impaired liver function, such as an increase in the level of liver enzymes in the serum, the development of hepatitis, including autoimmune, liver failure. However, it is not known whether this is a consequence of taking interferon beta-1a or concomitant therapy. Patients should be closely monitored for signs of impaired liver function, especially if interferon is used in conjunction with other hepatotoxic drugs.
When using Avonex®, patients with cardiovascular diseases should be carefully monitored: angina, myocardial infarction, cardiac failure, arrhythmia. Manifestations of an influenza-like syndrome caused by the use of the drug may aggravate the condition of such patients.
The use of interferons is accompanied by a number of abnormalities in laboratory indicators. Thus, in addition to routine laboratory tests during therapy with Avonex®, it is recommended to perform a detailed clinical analysis of blood with a leukocyte formula, counting the number of platelets,as well as a biochemical blood test, including monitoring the level of hepatic enzymes. Those patients who have there are signs of bone marrow depression, a more thorough examination of the blood may be required, with the determination of cell elements by fractions and platelets.
When treated with Avonex ®, it is possible to develop neutralizing antibodies. Neutralizing antibodies decrease the activity of interferon beta-1α in vitro. Neutralizing antibodies are also associated with a decrease in the biological effect of Avonex® in vivo and may potentially be associated with a decrease in the therapeutic effect. It is shown that the production of neutralizing antibodies reaches a plateau level after 12 months of therapy. According to recent clinical studies, antibodies to the Avonex® drug develop in 5-8% of patients undergoing therapy for 3 years.