XONVEA

Posology The recommended starting dose is two tablets (Total dose: 20 mg doxylamine succinate/20 mg pyridoxine hydrochloride) at bedtime (Day 1). If this dose adequately controls symptoms the next day, the patient can continue taking two tablets at bedtime.

However, if symptoms persist into the afternoon of Day 2, the patient should continue the usual dose of two tablets at bedtime (Day 2) and on Day 3 take three tablets (one tablet in the morning and two tablets at bedtime). If these three tablets do not adequately control symptoms on Day 3, the patient can take four tablets starting on Day 4 (one tablet in the morning, one tablet mid-afternoon and two tablets at bedtime).

The maximum recommended daily dose is four tablets (one in the morning, one in the mid-afternoon and two at bedtime). Xonvea should be taken as a daily prescription and not on an as needed basis. Continued need for Xonvea should be reassessed as the pregnancy progresses.

To prevent a sudden return of nausea and vomiting of pregnancy symptoms, a gradual tapering dose of Xonvea is recommended at the time of discontinuation. Paediatric population Xonvea is not indicated for use in children under 18 years of age.

1). No data are available. 5). Gastro-resistant tablets should be swallowed whole and should not be crushed, split or chewed to preserve the gastro-resistant properties.

a. Summary of the safety profile Adverse event information is derived from clinical trials and worldwide post- marketing experience. There has been clinical experience regarding the use of the Xonvea combination (doxylamine succinate and pyridoxine hydrochloride).

The incidence of treatment- emergent adverse events was similar for both treatment and placebo groups. The most frequently reported adverse reaction (≥5% and exceeding the rate in placebo) was somnolence. b. Tabulated list of adverse reactions The following listing of adverse reactions is based on clinical trial experience and/or post-marketing use.

Undesirable effects are displayed by MedDRA System Organ Classes and use the following conventions for frequency: 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).

The frequency of adverse reactions reported during post-marketing use cannot be determined as they are derived from spontaneous reports. Consequently, the frequency of these adverse events is qualified as "not known". System Organ Class Undesirable Effect Frequency Immune system disorders hypersensitivity Not known Psychiatric disorders anxiety, disorientation, insomnia, nightmares Not known somnolence Very common dizziness Common Nervous system disorders headache, migraines, paresthesia, psychomotor hyperactivity Not known Eye disorders vision blurred, visual disturbances Not known Ear and labyrinth disorders vertigo Not known Cardiac disorders dyspnea, palpitation, tachycardia Not known dry mouth CommonGastrointestinal disorders abdominal distention, abdominal pain, constipation, diarrhoea Not known Skin and subcutaneous tissue disorders hyperhidrosis, pruritus, rash, rash maculo-papular Not known Renal and urinary disorders dysuria, urinary retention Not known fatigue CommonGeneral disorders and administration site conditions chest discomfort, irritability, malaise Not known c.

5). 5). Possible adverse anticholinergic effects associated with the use of antihistamines as a class in general include: dryness of mouth, nose and throat; dysuria; urinary retention; vertigo, visual disturbances, blurred vision, diplopia, tinnitus; acute labyrinthitis; insomnia; tremors, nervousness; irritability; and facial dyskinesia.

Tightness of chest, thickening of bronchial secretions, wheezing, nasal stuffiness, sweating, chills, early menses, toxic psychosis, headache, faintness and paresthesia have occurred. Rarely, agranulocytosis, haemolytic anaemia, leukopenia, thrombocytopenia, and pancytopenia have been reported in a few patients receiving some antihistamines.

Increased appetite and/or weight gain also occurred in patients receiving antihistamines. d. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via <to be completed nationally>.

8). 5). Xonvea has anticholinergic properties and, therefore, should be used with caution in patients with: asthma, increased intraocular pressure, narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction and bladder-neck obstruction Xonvea contains pyridoxine hydrochloride, a vitamin B6 analog, therefore additional levels from diet and vitamin B6 supplements should be assessed.

There is limited evidence in cases of hyperemesis gravidarum for the combination doxylamine/pyridoxine These patients should be treated by a specialist. 5). Excipients This medicinal product contains the azo colouring agent Allura red AC aluminium lake (E 129) which may cause allergic reactions.

02 micrograms benzoic acid (E 210) in each gastro-resistant tablet. This medicinal product contains less than 1 mmol sodium (23 mg) per gastro- resistant tablet, that is to say essentially ‘sodium-free’.

1. 5).