Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: medac, Gesellschaft für klinische Spezialpräparate mbH, Theaterstr. 6, 22880 Wedel, Germany
Lomustine can cause birth defects. Men and women are recommended to take contraceptive precautions during therapy with lomustine and for 6 months after treatment. Men should be informed about the risk for an irreversible infertility due to treatment with lomustine (see section 4.6).
Lomustine “medac” should not be administered to patients who are pregnant or to mothers who are breastfeeding.
Other contraindications are:
Patients receiving Lomustine “medac” chemotherapy should be under the care of doctors experienced in cancer treatment. Delayed bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to bleeding and overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of lomustine.
Therefore, blood counts should be carried out before starting the medicinal product and at frequent intervals (preferably weekly for at least 6 weeks after a dose; see section 4.8) during treatment. Treatment and dosage is governed principally by the haemoglobin, white cell count and platelet count. Liver and kidney function should also be assessed periodically.
Patients must be strictly instructed not to use higher doses of lomustine than recommended by a physician and should be told that lomustine is taken as a single oral dose and will not be repeated for at least 6 weeks.
The bone marrow toxicity of lomustine is cumulative and therefore dose adjustments must be considered on the basis of nadir blood counts from prior dose.
Caution should be used in administering lomustine to patients with decreased circulating platelets, leukocytes, or erythrocytes.
Pulmonary toxicity from lomustine appears to be dose-related (see section 4.8). Baseline pulmonary function studies should be conducted along with frequent pulmonary function tests during treatment. Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLco) are particularly at risk.
Since lomustine may cause liver dysfunction, it is recommended that liver function tests be monitored periodically (see section 4.8).
Renal function tests should also be monitored periodically (see section 4.8).
Long term use of nitrosoureas has been reported to be possibly associated with the development of secondary malignancies.
Care must be taken whenever handling anticancer products. Steps should be taken to avoid exposure. This includes appropriate equipment, such as wearing gloves, and washing hands with soap and water after handling such products.
No interaction studies have been performed.
Lomustine “medac” use in combination with theophylline or with the H2 receptor antagonist cimetidine may potentiate bone marrow toxicity. Cross-resistance with other nitrosoureas is usual, but cross-resistance with conventional alkylating agents is unusual.
Pretreatment with phenobarbital can lead to a reduced antitumour effect of lomustine due to an accelerated elimination caused by induction of microsomal liver enzymes.
There is increased risk of fatal systemic vaccinal disease with the use of yellow fever vaccine. Live vaccines are contraindicated in immunosuppressed patients (see section 4.3).
Co-administration of antiepileptic medicinal products and chemotherapeutic medicinal products including lomustine can lead to complications secondary to pharmacokinetic interaction between the medicinal products.
Lomustine “medac” is contraindicated during pregnancy (see section 4.3). Safe use in pregnancy has not been established. Animal studies have shown reproductive toxicity (see section 5.3). If this medicinal product is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this medicinal product, the patient should be apprised of the potential hazard to the foetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Lomustine “medac” is contraindicated during breastfeeding (see section 4.3). Due to the lipophilic nature of lomustine, it is likely to be excreted in human milk. As a risk to the nursing child potentially exists, a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Lomustine “medac” therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Lomustine can have a mutagenic effect. Men treated with lomustine are therefore advised not to father children during treatment and for up to 6 months afterwards, and to seek advice regarding sperm conservation before the start of treatment given the possibility of irreversible infertility caused by lomustine therapy.
No studies on the effects on the ability to drive and use machines have been performed.
Lomustine “medac” capsules can impair the ability to drive and use machines, e.g. because of nausea and vomiting.
The list is presented by system organ class and frequency:
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)
Not known: Acute leukaemia, myelodysplastic syndrome
Very common: Leukopenia
Not known: Bone marrow failure, thrombocytopenia, anaemia
Not known: Coordination abnormal, disorientation, lethargy, dysarthria
Not known: Pulmonary fibrosis, lung infiltration
Not known: Nausea, vomiting, stomatitis
Not known: Transaminases increased, blood bilirubin increased
Not known: Alopecia
Not known: Renal failure, azotaemia, renal atrophy, renal injury
Not known: Blood alkaline phosphatase increased
The principal adverse effect is marrow toxicity of a delayed or prolonged nature. It usually occurs four to six weeks after administration of the medicinal product and is dose-related. Thrombocytopenia appears about four weeks after a dose of Lomustine “medac” and lasts one or two weeks at a level around 80-100,000/mm³. Leucopenia appears after five to six weeks and persists for one or two weeks at about 4-5,000/mm³.
The haematological toxicity may be cumulative, leading to successively lower white cell and platelet counts with successive doses of the medicinal product. Approximately 65 % of patients receiving 130 mg/m² develop white blood cell counts below 5,000 WBC/mm³. Thirty-six percent developed white blood cell counts below 3,000/mm³. Thrombocytopenia is generally more severe than leukopenia. However, both may be dose-limiting toxicities.
The occurrence of acute leukaemia and bone marrow dysplasia have been reported in patients following long-term nitrosourea therapy.
Anaemia also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia.
Nausea and vomiting usually occur four to six hours after a full single dose of Lomustine “medac” and last for 24–48 hours, followed by anorexia for two or three days. The effects are less troublesome if the 6-weekly dose is divided into three doses given on each of the first three days of the six week period. Gastrointestinal tolerance is usually good, however, if prophylactic antiemetics are given (e.g. metoclopramide or chlorpromazine). Disorders of liver function have been reported commonly. They are mild in most cases. In rare cases a cholestatic jaundice occurs. Transient elevation of liver enzymes (SGOT, SGPT, LDH or alkaline phosphatase) are occasionally observed.
More rarely patients are troubled by stomatitis and diarrhoea.
Mild neurological symptoms, like e.g. apathy, disorientation, confusion and stuttering can occur uncommonly in combination therapy with other antineoplastic medicinal products or radiation.
Interstitial pneumonia or lung fibrosis have been reported rarely.
Renal failure, decrease in kidney size, and progressive azotaemia have been reported in single cases after prolonged treatment with lomustine and related nitrosoureas reaching a high cumulative total dose. Therefore it is recommended not to exceed a maximum cumulative total lomustine dose of 1,000 mg/m².
Kidney damage has also been reported occasionally in patients receiving lower total doses.
Loss of scalp hair has been reported rarely.
In single cases an irreversible vision loss has been reported after a combined therapy of lomustine with radiation.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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