aAny severity grade.

bGrade 3= severe pain requiring analgesics (or narcotic analgesics for ≤ 72 hours) and/or limiting usual activities; Grade 4= severe pain requiring hospitalisation or prolongation of hospitalisation, resulting in death, or persistent or significant disability/incapacity, or life-threatening, or medically significant.

cGrade 3= ≥ 50 mm but < 85 mm average diameter; Grade 4= ≥ 85 mm average diameter.

dGrade 3= ≥ 25 mm but < 50 mm average diameter; Grade 4= ≥ 50 mm average diameter.

eGrade 3= ≥ 3 cm; Grade 4= If draining.

fGrade 3= refractory to topical treatment or requiring oral or parenteral treatment; Grade 4= not defined.

gGrade 3= > 3 cm but ≤ 5 cm; Grade 4= > 5 cm.

In addition there have been a small number of hypersensitivity reactions attributed to enfuvirtide and in some cases recurrence has occurred upon re-challenge (see section 4.4).

Other adverse reactions

In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).

Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see section 4.4).

As a peptide, enfuvirtide can cause cutaneous amyloidosis at the injection site.

Laboratory abnormalities

The majority of patients had no change in the toxicity grade of any laboratory parameter during the study except for those listed in Table 4. Through week 48, eosinophilia [greater than the Upper Limit of Normal of > 0.7 x 109/l] occurred at a higher rate amongst patients in the Fuzeon containing group (12.4 patients with event per 100 patient-years) compared with OB alone regimen (5.6 patients with event per 100 patient-years). When using a higher threshold for eosinophilia (>1.4 x 109/l), the patient exposure adjusted rate of eosinophilia is equal in both groups (1.8 patients with event per 100 patient-years).

Table 4: Exposure adjusted Grade 3 & 4 laboratory abnormalities among patients on Fuzeon+OB and OB alone regimens, reported at more than 2 patients with event per 100 patient years

Laboratory Parameters Grading
 Fuzeon+OB regimen

Per 100 patient years
 OB alone regimen

Per 100 patient years
 
n

(Total Exposure patient years)
 663

(557.0)
 334

(162.1)
 
ALAT
 
Gr. 3 (