BIOMAB EGFR Solution for infusion Ref.[49517] Active ingredients: Nimotuzumab

In a randomized clinical trial in patients with head and neck cancers where Nimotuzumab was used concurrently with or without RT and/or CT, the commonly reported adverse events in the radiotherapy group were fever, chills, mucositis, pruritis, urticaria/rash, headache, hypertension and fluctuation in blood pressure. The reported adverse events in the chemo radiotherapy group were mucositis, asthenia, dizziness, haematuria (microscopic), vomiting and loose stools. Only rash and chills was rated by the investigator as certainly related to Nimotuzumab. These adverse events were mild to moderate in severity, self-limiting reversible and probably or possibly related to Nimotuzumab. Three patients showed first dose infusion reaction and recovered without any sequelae and were able to withstand subsequent infusions of Nimotuzumab. One patient had a serious anaphylactic reaction with skin rash that was treated with symptomatic therapy and was withdrawn from the study.

In the chemo radiotherapy group the proportion of patients reporting grade III & IV adverse events in the Nimotuzumab arm was more than the arm without Nimotuzumab. These adverse events were related mostly to the concurrent CT+RT rather than to Nimotuzumab. The radiotherapy group showed proportion of patients with grade III & IV adverse events to be more in the arm without Nimotuzumab in relation to RT than the Nimotuzumab arm. Addition of Nimotuzumab has not shown to potentiate the toxic effects of RT.

The anaphylactic skin reaction was the only SAEs reported due to the Nimotuzumab. The other SAEs reported were due to the underlying malignant disorder or as a result of treatment with concurrent chemotherapy or radiotherapy.

In the clinical trial on advanced nasopharyngeal squamous carcinoma the most frequently observed adverse reaction include low fever, hypotension, nausea, dizziness and skin rash. Among the 70 patients of the experimental group treated with the drug, the incidence of Grade I fever, was 4.28%, and the highest temperature was 39°C, which decreased after treatment and did not interrupt the therapy schedule; the incidence of hypotension and dizziness was 2.86%, and the lowest blood pressure recorded was 80/50, which normalized after rest. The incidence of Grade I nausea and skin rash, was 1.43%.

Adverse reactions observed in clinical trials when Nimotuzumab was used along with radiotherapy for the treatment of advanced epidermal derived tumors in head and neck cancers were classified as common and rare reactions, and are listed in Table 1. Most of the adverse reactions related to the drug, were of Grade I and II severity. No skin rash or other skin toxicity was reported.

Table 1. Incidence of common adverse reactions in patients with advanced epidermal derived cancers:

In a single arm non randomized clinical trial one patient developed a grade 3 somnolence after his first dose. Other mild or moderate reactions were fever, vomiting, nausea, hypotension, tremors, chills, headache, disorientation, precordial pain, dysphasia and myalgias. These adverse events were controlled by standard medication. Irradiation toxicity was not exacerbated by the addition of Nimotuzumab to standard radiotherapy.

In the second non randomized study in SCCHN patients the most common radiation associated adverse events were taste alteration, dysphagia, stomatitis, mucositis, and pain in the throat and erythema in the radiation field. None of these were unexpected and there did not appear to be any exacerbation associated with administration of the antibody. Nausea and fatigue were the most commonly reported non-radiation associated adverse event. Infusion reactions occurred only in four patients receiving a single specific lot of Nimotuzumab. There were 13 SAEs reported. The serious adverse events reported were mainly due to disease progression or metastatic disease and were deemed not related to study therapy. This included two deaths; one patient died following hemorrhage from the esophageal component of his tumor and a second patient died due to unknown cause.

BIOMab EGFR should be used with caution in patients with known hypersensitivity to Nimotuzumab or to any of the known components of the formulation. (See DESCRIPTION for other components in the formulation).

Animal reproduction studies have not been conducted with Nimotuzumab. However, the EGFR has been implicated in the control of prenatal development and hence may be essential for normal organogenesis, proliferation, and differentiation in the developing embryo. Human IgG1 is known to cross the placental barrier; therefore the antibody has the potential to be transmitted from the mother to the developing fetus. But it is not known whether the antibody can cause fetal harm when administered to a pregnant woman. The antibody should only be given to a pregnant woman, or any woman not employing adequate contraception if the potential benefit outweighs the potential risk to the fetus. If the patient becomes pregnant while receiving this drug, she should be informed of the potential hazard to the fetus and/or the potential risk for loss of the pregnancy

It is not known whether the antibody is secreted in human milk. Since human IgG1 is secreted in human milk, the potential for absorption and harm to the infant after ingestion is unknown. No recommendation is made on the potential benefit versus risk of administering Nimotuzumab to nursing mothers.

Clinical studies are currently ongoing in pediatric patients with neurological tumors without significant adverse events related to Nimotuzumab.

Efficacy in heavily pretreated relapse high grade gliomas in children and adolescents has been demonstrated in a Phase II study. The repeated application of Nimotuzumab as monotherapy was well tolerated and safe. None of the SAEs was considered related to study medication. The clinical deteriorations were mostly associated with complications of the tumor disease, tumor progressions or, rarely, with another concomitant disease. In particular no allergic reactions or severe skin or gastrointestinal toxicity were observed.

No safety concerns arose from laboratory tests, vital signs, or physical examination findings. No severe hematological or non-hematological side effects associated with the Nimotuzumab antibody were seen, minimizing the risk of severe infections, blood transfusions and hospitalizations.

The maximum age limit evaluated in head and neck cancer clinical studies was 78 years. Clinical studies conducted with Nimotuzumab are not adequate to show any differences in response due to the effect of advanced age.

The effect of concomitant administration of other drugs on Nimotuzumab and the reverse has not been evaluated.