BENETOR 10mg, 20 mg and 40 mg film-coated tablets

Type IA - warning for autoimmune hepatitis

Type IA - warning for autoimmune hepatitis

Type IA - warning for autoimmune hepatitis

IA- warning for autoimmune hepatitis

Additional 4.1 text shown in bold

4.1       Therapeutic indications

Treatment of essential hypertension in adults.

Treatment of hypertension in children and adolescents from 6 to less than 18 years of age.

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4.2       Posology and method of administration

Posology

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Paediatric population

Children and adolescents from 6 to less than 18 years of age:

The recommended starting dose of olmesartan medoxomil in children from 6 to less than 18 years of age is 10 mg olmesartan medoxomil once daily. In children whose blood pressure is not adequately controlled at this dose, the dose of olmesartan medoxomil may be increased to 20 mg once daily. If additional blood pressure reduction is required, in children who weigh ≥ 35 kg, the olmesartan medoxomil dose may be increased to a maximum of 40 mg. In children who weigh < 35 kg, the daily dose should not exceed 20 mg.

Other paediatric population:

The safety and efficacy of olmesartan medoxomil in children aged 1 to 5 years old and adolescents below 18 years has have not yet been established. Currently available data are described in sections 4.8 and 5.1 and 5.2 but no recommendation on a posology can be made.

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4.5       Interaction with other medicinal products and other forms of interaction

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4.2       Posology and method of administration

Posology:

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Elderly Older people (65 years or older over)

No adjustment of dosage is generally required in elderly older people (see below for dose recommendations in patients with renal impairment). If up-titration to the maximum dose of 40 mg daily is required, blood pressure should be closely monitored.

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4.4       Special warnings and precautions for use

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Renal impairment and kidney transplantation:

When olmesartan medoxomil is used in patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. Use of olmesartan medoxomil is not recommended in patients with severe renal impairment (creatinine clearance < 20 mL/min) (see sections 4.2, 5.2). There is no experience of the administration of olmesartan medoxomil in patients with a recent kidney transplant or in patients with end-stage renal impairment (ie i.e. creatinine clearance <12 mL/min).

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Hyperkalaemia:

The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause hyperkalaemia.

The risk, that may be fatal, is increased in elderly older people, in patients with renal insufficiency and in diabetic patients, in patients concomitantly treated with other medicinal products that may increase potassium levels, and/or in patients with intercurrent events.

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Sprue-like enteropathy:

In very rare cases severe, chronic diarrhoea with substantial weight loss has been reported in patients taking olmesartan few months to years after drug initiation, possibly caused by a localized delayed hypersensitivity reaction. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan, and in the absence of other apparent etiologies, olmesartan treatment should be immediately discontinued and should not be restarted. If diarrhoea does not improve during the week after the discontinuation, further specialist (e.g. a gastro-enterologist) advice should be considered.exclude other etiologies. Consider discontinuation of olmesartan medoxomil in cases where no other etiology is identified. In cases where symptoms disappear and sprue-like enteropathy is confirmed by biopsy, treatment with olmesartan medoxomil should not be restarted.

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4.8       Undesirable effects

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Tabulated list of adverse reactions:

Adverse reactions from Benetor in clinical trials, post-authorisation safety studies and spontaneous reporting are summarized in the below table.

The following terminologies have been used in order to classify the occurrence of adverse reactions: 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).

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5.2       Pharmacokinetic properties

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Pharmacokinetics in special populations

Paediatric population:

The pharmacokinetics of olmesartan was studied in paediatric hypertensive patients aged 1 to 16 years. The clearance of olmesartan in paediatric patients was similar to that in adult patients when adjusted by the body weight.

There is no pharmacokinetic information available in renally impaired paediatric subjects.

Elderly Older people (age 65 years or older over):

In hypertensive patients, the AUC at steady state was increased by ca 35% in elderly older people (65 – 75 years old) and by ca 44% in very elderly old people (³ 75 years old) compared with the younger age group. This may be at least in part related to a mean decrease in renal function in this group of patients.

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10.       DATE OF (PARTIAL) REVISION OF THE TEXT

02/201601/2016

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4.2     Posology and method of administration

Posology:

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Paediatric population

The safety and efficacy of Benetor olmesartan medoxomil in children and adolescents below 18 years has not been established. No data are available. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

Olmesartan medoxomil should not be used in children below 1 years of age because of safety concerns and lack of data in this age group.

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Additional 4.8 text shown in bold – deleted shown in strike-through

4.8     Undesirable effects

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Additional information on special populations

Paediatric population

The safety of olmesartan medoxomil was monitored in 361 children and adolescents, aged 1-17 years old during 2 clinical trials. Whilst the nature and severity of the adverse events are similar to that of the adults, the frequency of the following is higher in the children:

-          Epistaxis is a common adverse event in children (i.e. ≥ 1/100 to < 1/10) that has not been reported in adults.

-          During the 3 weeks of double blind study, the incidence of treatment emergent dizziness and headache nearly doubled in children 6-17 years of age in the high olmesartan medoxomil dose group.

The overall safety profile for olmesartan medoxomil in paediatric patients does not differ significantly from the safety profile in adults.

Elderly (age 65 years or over)

In older elderly people the frequency of hypotension is slightly increased from rare to uncommon.

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5.1     Pharmacodynamic properties

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Paediatric population

The antihypertensive effects of Benetor in the paediatric population were evaluated in a randomized, double-blind, placebo-controlled study in 302 hypertensive patients aged 6 to 17 years. The study population consisted of an all black cohort of 112 patients and a mixed racial cohort of 190 patients, including 38 blacks. The etiology of the hypertension was predominantly essential hypertension (87% of the black cohort and 67% of the mixed cohort). Patients who weighed 20 to <35 kg were randomized to 2.5 mg (low dose) or 20 mg (high dose) of Benetor once daily and patients who weighed ≥35 kg were randomized to 5 mg (low dose) or 40 mg (high dose) of Benetor once daily. Benetor significantly reduced both systolic and diastolic blood pressure in a weight-adjusted dose-dependent manner. Benetor at both low and high doses significantly reduced systolic blood pressure by 6.6 and 11.9 mmHg from the baseline, respectively. This effect was also observed during the 2 weeks randomized withdrawal phase, whereby both mean systolic and diastolic blood pressures demonstrated a statistically significant rebound in the placebo group compared to Benetor group. The treatment was effective in both, paediatric patients with primary and secondary hypertension. As observed in adult populations, the blood pressure reductions were smaller in black patients.

In the same study, 59 patients aged 1 to 5 years who weighed ≥5 kg received 0.3 mg/kg of Benetor once daily for three weeks in an open label phase and then were randomized to receiving Benetor or placebo in a double-blind phase. At the end of the second week of withdrawal, the mean systolic/diastolic blood pressure at trough was 3/3 mmHg lower in the group randomized to Benetor; this difference in blood pressure was not statistically significant (95% C.I. -2 to 7/-1 to 7).

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Additional 5.2 text shown in bold

5.2     Pharmacokinetic properties

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Pharmacokinetics in special populations

Paediatric population:

The pharmacokinetics of olmesartan was studied in paediatric hypertensive patients aged 1 to 16 years. The clearance of olmesartan in paediatric patients was similar to that in adult patients when adjusted by the body weight.

There is no pharmacokinetic information available in renally impaired paediatric subjects.

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10.     DATE OF (PARTIAL) REVISION OF THE TEXT

01/2016 February 2015

Under Section 3:  Pharmaceutical Form, the information relating to the 20mg and 40mg tablets has been added as follows: 

Benetor 10 and 20 mg tablets: White, circular, film-coated tablets with C13 and C14 respectively embossed on one side.

Benetor 40 mg tablets: White, oval, film-coated tablets with C15 embossed on one side.