The CHMP reviewed the data submitted by Marketing Authorisation Holders from clinical trials, epidemiological studies, and spontaneous reporting of adverse drug reactions.

In the table below all medically important adverse reactions, which occurred in clinical trials at an incidence greater than placebo are listed by system organ class and frequency (very common (≥ 1/ 10),

Data possibly or probably related to Renagel from these studies (299 patients) and from uncontrolled clinical trials (384 patients) are listed by frequency in the table below.

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 detailed guidelines on the documentation relating to the clinical trial, which shall constitute the master file on the trial, archiving, qualifications of inspectors and inspection procedures to verify compliance of the clinical trial in question with this Directive shall be adopted and revised in accordance with the procedure referred to in Article 21(2).

10 Table 1 lists the adverse reactions based on experience from clinical studies as well as adverse reactions, some with fatal outcome, reported from post-marketing experience.

Table 1 contains very common (≥ 1/ 10) and common (≥ 1/ 100 to < 1/ 10) adverse reactions for which there is at least a reasonable suspicion of a causal relationship to INCRELEX treatment which occurred in clinical trials.

35 The ADRs reported from clinical studies, post-marketing experience and laboratory findings are listed below according to system organ class.

Pharyngitis*, infection viral* Bronchitis, sinusitis, herpes simplex (resistance), rhinitis Pneumonia§

Table 4 lists the adverse reactions recorded in clinical studies in the total safety population treated with Xolair by system organ class and by frequency.

The following side effects listing is based on reports from clinical trials with Extavia (List 1) and from side effects reported on the marketed product (List 2).

Regarding the indication in pain, the review of the previously available information and the review of the results of the newly conducted multicenter, placebo-controlled clinical study supports the use of Neurontin for the treatment of post-herpetic neuralgia and painful diabetic peripheral neuropathy.

No clinical studies in the treatment of complicated or life-threatening urinary tract infections with the high 1200mg [ or 1500 mg peroral ] maximum dose proposed, were included or reviewed.

Active surveillance implies definitive action intended to identify the presence of disease, such as systematic clinical inspections, ante and post mortem examination, serology on farm or in abattoir, referral of pathological material for laboratory diagnosis, sentinel animals.

not earlier than 28 days after the last re-introduction, all animals must be clinically examined and samples for testing for the presence of antibody against foot-and-mouth disease virus shall be taken in accordance with the requirements of point 2.2 of Annex III;

This provision will apply inter alia to the manufacture of active pharmaceutical ingredients and intermediate products and products intended for use in clinical trials, as well as agreed pre-marketing inspections.

Commission Decision 92/432/EEC of 23 July 1992 laying down certain conditions under which a derogation may be made from the principle of individual clinical examination of animals entering the Community from third countries (OJ L 237, 20.8.1992, p. 29).

In clinical studies involving healthy subjects who received 1 dose of Varicella Vaccine live (Oka/ Merck), detectable varicella antibodies were present in most individuals tested for up to 10 years postvaccination.

Following this request, the CHMP reviewed the available data on this safety issue, including post-marketing reports, data from non- clinical studies, clinical trials and epidemiological studies.

the meat is detained under official control for 24 hours and not released before a repeat inspection of the animals in the holding of origin has ruled out on clinical inspection the presence of infected or suspected of being infected animals.

Clinical response In all studies, patients treated with tocilizumab 8 mg/ kg had statistically significant higher ACR 20, 50, 70 response rates at 6 months compared to control (Table 2).

Patients receiving concomitant treatment with anti-coagulants (e. g. warfarin; acenocumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/ INR), and physical examination.

With respect to the maximal dose, the applicant reviewed 6 clinical studies addressing the safety and efficacy of the proposed high dose ciprofloxacin treatment regimens in critically ill patients.

The sentinel piglets shall be placed, in accordance with the requirements of the competent authority, throughout the infected holding and will be examined clinically 28 days after having been placed on the holding, and sampled for serological testing.

The incidence of adverse reactions possibly reflecting meningeal irritation determined from all the patients treated with 50 mg DepoCyte in the Phase II-IV clinical trials is given in Table 1 below:

It will meet twice a year and review all clinical trial, pharmaco- epidemiology and post marketing safety data obtained with pimecrolimus.

In two single-dose trials, Aerius oral lyophilisate was well tolerated as documented by clinical laboratory findings, physical examinations, vital signs, and ECG interval data.

In two single-dose trials, Azomyr oral lyophilisate was well tolerated as documented by clinical laboratory findings, physical examinations, vital signs, and ECG interval data.

No clinical studies in the treatment of complicated or life-threatening urinary tract infections with the high 1200 mg intravenous [ or 1500 mg peroral ] maximum dose proposed, were included or reviewed.

Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials (comprising a total of 5253 patients, 3289 on duloxetine and 1964 on placebo).

Table 4, below provides the schedule followed for other dose modifications in the clinical trial in the treatment of patients with multiple myeloma receiving Caelyx and bortezomib combination therapy.

In two single-dose trials, Neoclarityn oral lyophilisate was well tolerated as documented by clinical laboratory findings, physical examinations, vital signs, and ECG interval data.

4 The following table of undesirable effects (first year of treatment) is based on adverse events that occurred at a frequency of > 2 % and with an incidence ≥ 1 % above placebo in clinical trials of 1 and 2 years duration:

In controlled clinical trials, the following adverse reactions were reported in ≥ 1 % of patients with either concomitantly administered amlodipine plus lisinopril or with amlodipine and lisinopril monotherapies (see Table below):

Table 2 Adverse reactions very commonly and commonly reported in paediatric clinical trials  13 Very common (≥1/10) - Common (≥1/100, < 1/10) System Organ Class Infection and infestations

Clinical trial data and post-marketing data Table 3 presents adverse reactions by system organ class and by frequency category based on experience with glimepiride and other sulphonylureas.

The adverse reactions listed in Table 4 are based on experience from clinical trials in adult naïve patients treated for 1 year and post-marketing use.

Table 1 lists adverse drug reactions (ADRs) reported for the 153 patients treated with Replagal in clinical trials, including 21 patients with history of endstage renal disease and 17 female patients.

'(c) have been submitted to a health examination by an official veterinarian or authorized veterinarian during the 48 hours preceding consignment and, at the time of the examination, have presented no clinical sign or suspicion of contagious poultry disease;'.

Table 4 lists ADRs associated with the use of Xeloda monotherapy based on a pooled analysis of safety data from three major studies including over 1900 patients (studies M66001, SO14695, and SO14796).

'(c) where the health examination carried out by the official veterinarian or authorized veterinarian during the 5 days preceding dispatch on the flock from which the consignment to be slaughtered is to be drawn has not revealed within that flock any clinical sign or suspicion of contagious poultry disease;'.

Member States shall ensure that when the presence of swine vesicular disease virus is suspected in a holding, a statistically significant number of pigs are checked by the official veterinarian as quickly as possible to detect the clinical signs of disease referred to in Chapter IX.

all animals accommodated in the semen collection centre have undergone a clinical examination, and samples taken in accordance with point 2.2 of Annex III have been subjected to a serological test to substantiate the absence of infection in the semen collection centre concerned, and

The concomitant administration of EXJADE with anticoagulants may also increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.

In all cases this was mild or moderate on physical examination and the clinical course was benign; no patients had a diagnosis of hypersplenism and no patients underwent splenectomy.

In the clinical studies with PhotoBarr, follow-up surveillance was done every three months, or every six months after four consecutive biopsy results had shown no more high-grade dysplasia (see section 5.1).

The person participating in a trial must consent to the scrutiny of personal information during inspection by competent authorities and properly authorised persons, provided that such personal information is treated as strictly confidential and is not made publicly available.

The review of available guidelines and clinical efficacy data showed that moxifloxacin can be used for treatment of PID in the sense of a monotherapy only after results of microbiological testing are available.

It is therefore necessary to simplify and harmonise the administrative provisions governing such trials by establishing a clear, transparent procedure and creating conditions conducive to effective coordination of such clinical trials in the Community by the authorities concerned.

Liver function tests should be performed in all patients: at initiation of treatment and then periodically after around six weeks (end of acute phase), after around twelve and twenty four weeks (end of maintenance phase) and thereafter when clinically indicated. Any patient who develops