1. Name Of The Medicinal Product
IntronA 18, 30 or 60 million IU solution for injection, in multidose pen
2. Qualitative And Quantitative Composition
One pen contains 18, 30 or 60 million IU of recombinant interferon alfa-2b produced in E. coli by recombinant DNA technology in 1.2 ml solution.
One ml contains 15, 25 or 50 million IU of interferon alfa-2b.
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Solution for injection
Clear and colourless solution.
4. Clinical Particulars
4.1 Therapeutic Indications
Chronic hepatitis B
Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B viral replication (presence of DNA of hepatitis B virus (HBV-DNA) and hepatitis B antigen (HBeAg), elevated alanine aminotransferase (ALT) and histologically proven active liver inflammation and/or fibrosis.
Chronic hepatitis C
Before initiating treatment with IntronA, consideration should be given to the results from clinical trials comparing IntronA with pegylated interferon (see section 5.1).
Adult patients
IntronA is indicated for the treatment of adult patients with chronic hepatitis C who have elevated transaminases without liver decompensation and who are positive for hepatitis C virus RNA (HCV-RNA) (see section 4.4).
The best way to use IntronA in this indication is in combination with ribavirin.
Children 3 years of age and older and adolescents
IntronA is indicated in a combination regimen with ribavirin, for the treatment of children 3 years of age and older and adolescents, who have chronic hepatitis C, not previously treated, without liver decompensation, and who are positive for HCV-RNA.
When deciding not to defer treatment until adulthood, it is important to consider that the combination therapy induced a growth inhibition. The reversibility of growth inhibition is uncertain
The decision to treat should be made on a case by case basis (see section 4.4).
Hairy cell leukaemia
Treatment of patients with hairy cell leukaemia.
Chronic myelogenous leukaemia
Monotherapy
Treatment of adult patients with Philadelphia chromosome or bcr/abl translocation positive chronic myelogenous leukaemia.
Clinical experience indicates that a haematological and cytogenetic major/minor response is obtainable in the majority of patients treated. A major cytogenetic response is defined by < 34 % Ph+ leukaemic cells in the bone marrow, whereas a minor response is
Combination therapy
The combination of interferon alfa-2b and cytarabine (Ara-C) administered during the first 12 months of treatment has been demonstrated to significantly increase the rate of major cytogenetic responses and to significantly prolong the overall survival at three years when compared to interferon alfa-2b monotherapy.
Multiple myeloma
As maintenance therapy in patients who have achieved objective remission (more than 50 % reduction in myeloma protein) following initial induction chemotherapy.
Current clinical experience indicates that maintenance therapy with interferon alfa-2b prolongs the plateau phase; however, effects on overall survival have not been conclusively demonstrated.
Follicular lymphoma
Treatment of high tumour burden follicular lymphoma as adjunct to appropriate combination induction chemotherapy such as a CHOP-like regimen. High tumour burden is defined as having at least one of the following: bulky tumour mass (> 7 cm), involvement of three or more nodal sites (each > 3 cm), systemic symptoms (weight loss > 10 %, pyrexia > 38°C for more than 8 days, or nocturnal sweats), splenomegaly beyond the umbilicus, major organ obstruction or compression syndrome, orbital or epidural involvement, serous effusion, or leukaemia.
Carcinoid tumour
Treatment of carcinoid tumours with lymph node or liver metastases and with “carcinoid syndrome”.
Malignant melanoma
As adjuvant therapy in patients who are free of disease after surgery but are at high risk of systemic recurrence, e.g., patients with primary or recurrent (clinical or pathological) lymph node involvement.
4.2 Posology And Method Of Administration
Treatment must be initiated by a physician experienced in the management of the disease.
Multidose presentations must be for individual patient use only.
IntronA 18 million IU solution for injection, multidose pen
The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU. The pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 4 weeks.
IntronA 30 million IU solution for injection, multidose pen
The pen is designed to deliver its contents of 30 million IU in doses ranging from 2.5 to 10 million IU. The pen will deliver a maximum of 12 doses of 2.5 million IU over a period not to exceed 4 weeks.
IntronA 60 million IU solution for injection, multidose pen
The pen is designed to deliver its contents of 60 million IU in doses ranging from 5 to 20 million IU. The pen will deliver a maximum of 12 doses of 5 million IU over a period not to exceed 4 weeks.
Not all dose forms and strengths are appropriate for some indications. Appropriate dose form and strength must be selected.
If adverse events develop during the course of treatment with IntronA for any indication, modify the dose or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance develops following adequate dose adjustment, or disease progresses, discontinue treatment with IntronA. At the discretion of the physician, the patient may self-administer the dose for maintenance dose regimens administered subcutaneously.
Chronic hepatitis B
The recommended dose is in the range 5 to 10 million IU administered subcutaneously three times a week (every other day) for a period of 4 to 6 months.
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe thrombocytopaenia (< 70,000/mm3).
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the maximum tolerated dose), discontinue IntronA therapy.
Chronic hepatitis C
Adults
IntronA is administered subcutaneously at a dose of 3 million IU three times a week (every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin.
Children 3 years of age or older and adolescents
IntonA 3 MIU/m2 is administered subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution administered orally in two divided doses daily with food (morning and evening).
(See ribavirin capsules SPC for dose of ribavirin capsules and dose modification guidelines for combination therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution SPC)
Relapse patients (adults)
IntronA is given in combination with ribavirin. Based on the results of clinical trials, in which data are available for 6 months of treatment, it is recommended that patients be treated with IntronA in combination with ribavirin for 6 months.
Naïve patients (adults)
The efficacy of IntronA is enhanced when given in combination with ribavirin. IntronA should be given alone mainly in case of intolerance or contraindication to ribavirin.
- IntronA in combination with ribavirin
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is recommended that patients be treated with IntronA in combination with ribavirin for at least 6 months.
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and high pre-treatment viral load.
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into account in order to extend therapy to 12 months.
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower limit of detection six months after withdrawal of treatment).
- IntronA alone:
The optimal duration of therapy with IntronA alone is not yet fully established, but a therapy of between 12 and 18 months is advised.
It is recommended that patients be treated with IntronA alone for at least 3 to 4 months, at which point HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative HCV-RNA.
Naïve patients (children and adolescents)
The efficacy and safety of IntronA in combination with ribavirin has been studied in children and adolescents who have not been previously treated for chronic hepatitis C.
Duration of treatment for children and adolescents
• Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive value 96 %). Therefore, it is recommended that children and adolescent patients receiving IntronA/ribavirin combination be discontinued from therapy if their week 12 HCV-RNA dropped < 2 log10 compared to pretreatment, or if they have detectable HCV-RNA at treatment week 24.
• Genotype 2/3: The recommended duration of treatment is 24 weeks.
Hairy cell leukaemia
The recommended dose is 2 million IU/m2 administered subcutaneously three times a week (every other day) for both splenectomised and non-splenectomised patients. For most patients with Hairy Cell Leukaemia, normalisation of one or more haematological variables occurs within one to two months of IntronA treatment. Improvement in all three haematological variables (granulocyte count, platelet count and haemoglobin level) may require six months or more. This regimen must be maintained unless the disease progresses rapidly or severe intolerance is manifested.
Chronic myelogenous leukaemia
The recommended dose of IntronA is 4 to 5 million IU/m2 administered daily subcutaneously. Some patients have been shown to benefit from IntronA 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg). When the white blood cell count is controlled, administer the maximum tolerated dose of IntronA (4 to 5 million IU/m2 daily) to maintain haematological remission.
IntronA treatment must be discontinued after 8 to 12 weeks of treatment if at least a partial haematological remission or a clinically meaningful cytoreduction has not been achieved.
Multiple myeloma
Maintenance therapy
In patients who are in the plateau phase (more than 50 % reduction of myeloma protein) following initial induction chemotherapy, interferon alfa-2b may be administered as monotherapy, subcutaneously, at a dose of 3 million IU/m2 three times a week (every other day).
Follicular lymphoma
Adjunctively with chemotherapy, interferon alfa-2b may be administered subcutaneously, at a dose of 5 million IU three times a week (every other day) for a duration of 18 months. CHOP-like regimens are advised, but clinical experience is available only with CHVP (combination of cyclophosphamide, doxorubicin, teniposide and prednisolone).
Carcinoid tumour
The usual dose is 5 million IU (3 to 9 million IU) administered subcutaneously three times a week (every other day). Patients with advanced disease may require a daily dose of 5 million IU. The treatment is to be temporarily discontinued during and after surgery. Therapy may continue for as long as the patient responds to interferon alfa-2b treatment.
Malignant melanoma
As induction therapy, interferon alfa-2b is administered intravenously at a dose of 20 million IU/m2 daily for five days a week for a four-week period; the calculated interferon alfa-2b dose is added to sodium chloride 9 mg/ml (0.9 %)solution for injection and administered as a 20-minute infusion (see section 6.6). As maintenance treatment, the recommended dose is 10 million IU/m2 administered subcutaneously three days a week (every other day) for 48 weeks.
If severe adverse events develop during interferon alfa-2b treatment, particularly if granulocytes decrease to < 500/mm3 or alanine aminotransferase/aspartate aminotransferase (ALT/AST) rises to > 5 x upper limit of normal, discontinue treatment temporarily until the adverse event abates. Interferon alfa-2b treatment is to be restarted at 50 % of the previous dose. If intolerance persists after dose adjustment or if granulocytes decrease to < 250/mm3 or ALT/AST rises to > 10 x upper limit of normal, discontinue interferon alfa-2b therapy.
Although the optimal (minimum) dose for full clinical benefit is unknown, patients must be treated at the recommended dose, with dose reduction for toxicity as described.
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients.
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent myocardial infarction, severe arrhythmic disorders.
- Severe renal or hepatic dysfunction; including that caused by metastases.
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4).
- Chronic hepatitis with decompensated cirrhosis of the liver.
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive agents excluding short term corticosteroid withdrawal.
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients.
- Pre-existing thyroid disease unless it can be controlled with conventional treatment.
- Combination of IntronA with telbivudine.
Children and adolescents:
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicide attempt.
Combination therapy with ribavirin
Also see ribavirin SPC if IntronA is to be administered in combination with ribavirin in patients with chronic hepatitis C.
4.4 Special Warnings And Precautions For Use
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Hypersensitivity reactions
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon alfa-2b have been observed rarely during IntronA therapy. If such a reaction develops, discontinue the medicne and institute appropriate medical therapy. Transient rashes do not necessitate interruption of treatment.
Adverse experiences including prolongation of coagulation markers and liver abnormalities
Moderate to severe adverse experiences may require modification of the patient's dose regimen, or in some cases, termination of IntronA therapy.
Discontinue treatment with IntronA in patients with chronic hepatitis who develop prolongation of coagulation markers which might indicate liver decomposition.
Any patient developing liver function abnormalities during treatment with IntronA must be monitored closely and treatment discontinued if signs and symptoms progress.
Hypotension
Hypotension may occur during IntronA therapy or up to two days post-therapy and may require supportive treatment.
Need for adequate hydration
Adequate hydration must be maintained in patients undergoing IntronA therapy since hypotension related to fluid depletion has been seen in some patients. Fluid replacement may be necessary.
Pyrexia
While pyrexia may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of persistent pyrexia must be ruled out.
Patients with debilitating medical conditions
IntronA must be used cautiously in patients with debilitating medical conditions, such as those with a history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, pulmonary embolism) or severe myelosuppression.
Pulmonary conditions
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA. The aetiology has not been defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is administered concomitantly with interferon alpha (see section 4.5). Any patient developing pyrexia, cough, dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with corticosteroids appear to be associated with resolution of pulmonary adverse events.
Ocular adverse events
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery or vein obstruction have been reported in rare instances after treatment with alpha interferons. All patients should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, or reporting other ophthalmologic symptoms during treatment with IntronA, must have a prompt and complete eye examination. Periodic visual examinations during IntronA therapy are recommended particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or hypertension. Discontinuation of IntronA should be considered in patients who develop new or worsening ophthalmological disorders.
Obtundation, coma and encephalopathy
More significant obtundation and coma, including cases of encephalopathy, have been observed in some patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of IntronA.
Patients with pre-existing cardiac abnormalities
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current arrhythmic disorders, who require IntronA therapy, must be closely monitored. It is recommended that those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily supraventricular) usually respond to conventional therapy but may require discontinuation of IntronA therapy. There are no data in children or adolescents with a history of cardiac disease.
Hypertriglyceridemia
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. Monitoring of lipid levels is, therefore, recommended.
Patients with psoriasis and sarcoidosis
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of IntronA in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the potential risk.
Kidney and liver graft rejection
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney graft rejection. Liver graft rejection has also been reported.
Auto-antibodies and autoimmune disorders
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, Monotherapy (thyroid abnormalities) and section 4.8).
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and corticosteroid therapy discussed (see section 4.8).
Concomitant chemotherapy
Administration of IntronA in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration), which may be life-threatening or fatal as a result of the concomitantly administered medicinal product. The most commonly reported potentially life-threatening or fatal adverse events include mucositis, diarrhoea, neutropaenia, renal impairment, and electrolyte disturbance. Because of the risk of increased toxicity, careful adjustments of doses are required for IntronA and for the concomitant chemotherapeutic agents (see section 4.5). When IntronA is used with hydroxyurea, the frequency and severity of cutaneous vasculitis may be increased.
Chronic hepatitis C
Combination therapy with ribavirin
Also see ribavirin SPC if IntronA is to be administered in combination with ribavirin in patients with chronic hepatitis C.
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Monotherapy:
Infrequently, adult patients treated for chronic hepatitis C with IntronA developed thyroid abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using IntronA therapy, 2.8 % patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy for thyroid dysfunction. The mechanism by which IntronA may alter thyroid status is unknown. Prior to initiation of IntronA therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional therapy. IntronA treatment may be initiated if TSH levels can be maintained in the normal range by medication. Determine TSH levels if, during the course of IntronA therapy, a patient develops symptoms consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, IntronA treatment may be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of IntronA therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and adolescents, Thyroid monitoring).
Thyroid supplemental monitoring specific for children and adolescents:
Approximately 12 % of children treated with interferon alfa-2b and ribavirin combination therapy developed increase in thyroid stimulating hormone (TSH). Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of IntronA therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be treated with conventional therapy. IntronA therapy may be initiated if TSH levels can be maintained in the normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has been observed. If thyroid abnormalities are detected, the patient's thyroid status should be evaluated and treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence of thyroid dysfunction (e.g. TSH).
HCV/HIV Coinfection
Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy (HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding IntronA and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with IntronA and ribavirin combination therapy and zidovudine could be at increased risk of developing anaemia.
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may increase the risk in this patient subset.
Dental and periodontal disorders
Dental and periodontal disorders, which may lead to loss of teeth, have been reported in patients receiving IntronA and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of IntronA and ribavirin. Patients should brush their teeth thoroughly twice daily and have regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they should be advised to rinse out their mouth thoroughly afterwards.
Laboratory Tests
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all patients prior to and periodically during systemic treatment with IntronA.
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and every other month, thereafter, throughout treatment. If ALT flares during IntronA therapy to greater than or equal to 2 times baseline, IntronA therapy may be continued unless signs and symptoms of liver failure are observed. During ALT flare, the following liver function tests must be monitored at two-week intervals: ALT, prothrombin time, alkaline phosphatase, albumin and bilirubin.
In patients treated for malignant melanoma, liver function and white blood cell (WBC) count and differential must be monitored weekly during the induction phase of therapy and monthly during the maintenance phase of therapy.
Effect on fertility
Interferon may impair fertility (see section 4.6 and section 5.3).
Important information about some of the ingredients of IntronA
This medicinal product contains less than 1 mmol sodium (23 mg) per 1.2 ml, i.e., essentially “sodium-free”.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with IntronA.
Interactions between IntronA and other medicinal products have not been fully evaluated. Caution must be exercised when administering IntronA in combination with other potentially myelosuppressive agents.
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be monitored and dose adjusted if necessary.
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA. The aetiology has not been defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is administered concomitantly with interferon alpha (see section 4.4).
Administration of IntronA in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration) (see section 4.4).
Also see ribavirin SPC if IntronA is to be administered in combination with ribavirin in patients with chronic hepatitis C.
A clinical trial investigating the combination of telbivudine, 600 mg daily, with pegylated interferon alfa-2a, 180 micrograms once weekly by subcutaneous administration, indicates that this combination is associated with an increased risk of developing peripheral neuropathy. The mechanism behind these events is not known (see sections 4.3, 4.4 and 4.5 of the telbivudine SPC). Moreover, the safety and efficacy of telbivudine in combination with interferons for the treatment of chronic hepatitis B has not been demonstrated. Therefore, the combination of IntronA with telbivudine is contraindicated (see section 4.3).
4.6 Pregnancy And Lactation
Women of childbearing potential/contraception in males and females
Women of childbearing potential have to use effective contraception during treatment. Decreased serum estradiol and progesterone concentrations have been reported in women treated with human leukocyte interferon.
IntronA must be used with caution in fertile men.
Combination therapy with ribavirin
Ribavirin causes serious birth defects when administered during pregnancy. Extreme care must be taken to avoid pregnancy in female patients or in partners of male patients taking IntronA in combination with ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded. Male patients and their female partners must each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see ribavirin SPC).
Pregnancy
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. IntronA is to be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Combination therapy with ribavirin
Ribavirin therapy is contraindicated in women who are pregnant.
Breast-feeding
It is not known whether the components of this medicinal product are excreted in human milk. Because of the potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of treatment.
4.7 Effects On Ability To Drive And Use Machines
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with IntronA, and therefore it is recommended that they avoid driving or operating machinery.
4.8 Undesirable Effects
See ribavirin SPC for ribavirin-related undesirable effects if IntronA is to be administered in combination with ribavirin in patients with chronic hepatitis C.
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable effects were pyrexia, fatigue, headache and myalgia. Pyrexia and fatigue were often reversible within 72 hours of interruption or cessation of treatment.
Adults
In clinical trials conducted in the hepatitis C population, patients were treated with IntronA alone or in combination with ribavirin for one year. All patients in these trials received 3 MIU of IntronA three times a week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (>1/1,000 to <1/100); rarely (
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