Fuzeon · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-093674 · has-adverse-reaction-information · PDF-Seite 5

a. Summary of the safety profile Safety data mainly refer to 48-week data from studies TORO 1 and TORO 2 combined (see section 5.1). Safety results are expressed as the number of patients with an adverse reaction per 100 patient-years of exposure (except for injection site reactions). The most frequently reported events were injection site reactions, diarrhoea and nausea. The addition of Fuzeon to background antiretroviral therapy generally did not increase the frequency or severity of most adverse reactions. b. Tabulated list of adverse reactions Table 2 presents events seen at a higher rate among patients receiving Fuzeon + OB regimen than among patients on the OB alone regimen with an exposure adjusted increase of at least 2 patients with event per 100 patient-years. A statistically significant increase was seen for pneumonia and lymphadenopathy. Most adverse reactions were of mild or moderate intensity. Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined 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). 5 Table 2: Adverse reactions attributed to treatment with Fuzeon in studies TORO 1 and TORO 2 combined System organ class Adverse reaction Frequency Infections and infestations Common Sinusitis, skin papilloma, influenza, pneumonia, ear infection Blood and lymphatic system disorders Common Lymphadenopathy Metabolism and nutrition disorders Common Appetite decreased, anorexia, hypertriglyceridaemia, blood triglycerides increased, diabetes mellitus Psychiatric disorders Common Anxiety, nightmare, irritability Nervous system disorders Very common Peripheral neuropathy Common Hypoaesthesia, disturbance in attention, tremor Eye disorders Common

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HOS-093670 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-093669 · has-indication-information · PDF-Seite 2

Fuzeon is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected patients who have received treatment with and failed on regimens containing at least one medicinal product from each of the following antiretroviral classes: protease inhibitors, non- nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors, or who have intolerance to previous antiretroviral regimens (see section 5.1). In deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different medicinal products. Where available, resistance testing may be appropriate (see sections 4.4 and 5.1).

HOS-093672 · has-interaction-information · PDF-Seite 4

Interaction studies have only been performed in adults. No clinically significant pharmacokinetic interactions are expected between enfuvirtide and concomitantly given medicinal products metabolised by CYP450 enzymes. Influence of enfuvirtide on metabolism of concomitant medicinal products: In an in-vivo human metabolism study enfuvirtide, at the recommended dose of 90 mg twice daily, did not inhibit the metabolism of substrates by CYP3A4 (dapsone), CYP2D6 (debrisoquine), CYP1A2 (caffeine), CYP2C19 (mephenytoin), and CYP2E1 (chlorzoxazone). Influence of concomitant medicinal products on enfuvirtide metabolism: In separate pharmacokinetic interaction studies, co-administration of ritonavir (potent CYP3A4 inhibitor) or saquinavir in combination with a booster dose of ritonavir or rifampicin (potent CYP3A4 inducer) did not result in clinically significant changes of the pharmacokinetics of enfuvirtide. 4

HOS-093673 · has-pregnancy-information · PDF-Seite 5

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Animal studies do not indicate harmful effects with respect to foetal development. Enfuvirtide should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Breast-feeding: It is not known whether enfuvirtide is secreted in human milk. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV and any possible undesirable effects in breast-fed infants.

HOS-093671 · has-warning-information · PDF-Seite 3

Fuzeon must be taken as part of a combination regimen. Please also refer to the respective summary of product characteristics of the other antiretroviral medicinal products used in the combination. As with other antiretrovirals, enfuvirtide should optimally be combined with other antiretrovirals to which the patient’s virus is sensitive (see section 5.1). Patients should be informed that Fuzeon is not a cure for HIV-1 infection. Animal studies have shown that enfuvirtide may impair some immune functions (see section 5.3). In clinical trials, an increased rate of some bacterial infections, most notably a higher rate of pneumonia, was seen in patients treated with Fuzeon; however, an increased risk of bacterial pneumonia related to the use of Fuzeon has not been confirmed by subsequent epidemiological data. Hypersensitivity reactions have occasionally been associated with therapy with enfuvirtide and in rare cases hypersensitivity reactions have recurred on rechallenge. Events included rash, fever, nausea and vomiting, chills, rigors, low blood pressure and elevated serum liver transaminases in various combinations, and possibly primary immune complex reaction, respiratory distress and glomerulonephritis. Patients developing signs/symptoms of a systemic hypersensitivity reaction should discontinue enfuvirtide treatment and should seek medical evaluation immediately. Therapy with 3 enfuvirtide should not be restarted following systemic signs and symptoms consistent with a hypersensitivity reaction considered related to enfuvirtide. Risk factors that may predict the occurrence or severity of hypersensitivity to enfuvirtide have not been identified. Liver disease: The safety and efficacy of enfuvirtide has not been specifically studied in patients with significant underlying liver disorders. Patients with chronic hepatitis B and C and treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse events. Few patients included in the phase III trials were co-infected with hepatitis B/C. In these the addition of Fuzeon did not increase the incidence of hepatic events. In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products. Administration of Fuzeon to non-HIV-1 infected individuals may induce anti-enfuvirtide antibodies that cross-react with HIV gp41. This may result in

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