Section 4.2 - Addition of text with regards to reducing the dose in patients with renal/hepatic impairment. Addition of text regarding the mode of administration.

Section 4.3 - 'myasthenia gravis' moved to section 4.4. Addition of 'severe hepatic insufficiency'.

Section 4.4 - Addition of the following text - 'myasthenia gravis, coma or a known history of drug or alcohol abuse', ’Elderly or debilitated patients are more prone to the CNS effects of benzodiazepines and, therefore, lower doses are required (see 4.2 Posology and Method of Administration)’, ‘The dependence potential of midazolam increases with dose and duration of treatment and is greater in patients with a history of alcohol or drug abuse’ and ‘abrupt discontinuation should be avoided’.

Section 4.5 – Section re-structured into sub-headings. 

Addition of ‘nefazodone’ (antidepressants).

Addition of the following sub-headings and text – ‘Antihypertensives’, ‘Antivirals’, ‘Nicotine’, ‘NSAIDs’, ‘Probenecid’, ‘Xanthines’ and ‘Nabilone’.  Additional text under sub-heading ‘Antipsychotics’.

Section 4.6 – Addition of the following text:

‘There may be a small increase in the risk of congenital malformation, particularly oral cleft, with the use of benzodiazepines in the first trimester’

‘Infants born to mothers who take benzodiazepines chronically during the latter stages of pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. A small number of children exposed in utero to benzodiazepines have shown slow development in the early years but by four years of age have developed normally’.

Section 4.8 – Section re-structured into sub-headings. 

Addition of ‘hypotension’, ‘cardiac arrest’ (cardiovascular), ‘hiccups’ (general), ‘extrapyramidal’ (neurological), ‘postoperative delirium’ (psychiatric), ‘incontinence’ (urinary).

Addition of text relating to dosage (CNS).

Addition of paragraph ‘Withdrawal symptoms’

Deletion of ‘menstrual disturbances’ and ‘laryngeal spasm’.

Section 4.9 – Amendment of text under sub-heading ‘Symptoms’.

Addition of text ‘Cardiac rate and rhythm remain normal in the absence of anoxia or severe hypotension’.

Addition of text under sub-heading ‘Treatment’ regarding expert advice.

Section 6.2 – Addition of ‘dimenhydrinate, foscarnet sodium, imipenem with cilastin, pentobarbital sodium’ and ‘including parenteral solutions’.