4.1. Therapeutic indications

Treatment of essential hypertension.

Sevikar is indicated in adult patients whose blood pressure is not adequately controlled on olmesartan medoxomil or amlodipine monotherapy (see section 4.2 and section 5.1).

4.2. Posology and method of administration

Posology

Adults

The recommended dosage of Sevikar is 1 tablet per day.

Sevikar 20 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled by 20 mg olmesartan medoxomil or 5 mg amlodipine alone.

Sevikar 40 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled by Sevikar 20 mg/5 mg.

Sevikar 40 mg/10 mg may be administered in patients whose blood pressure is not adequately controlled by Sevikar 40 mg/5 mg.

A step-wise titration of the dosage of the individual components is recommended before changing to the fixed combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered.

For convenience, patients receiving olmesartan medoxomil and amlodipine from separate tablets may be switched to Sevikar tablets containing the same component doses.

Sevikar can be taken with or without food.

Elderly (age 65 years or over)

No adjustment of the recommended dose is generally required for elderly people but increase of the dosage should take place with care (see sections 4.4 and 5.2).

If up-titration to the maximum dose of 40 mg olmesartan medoxomil daily is required, blood pressure should be closely monitored.

Renal impairment

The maximum dose of olmesartan medoxomil in patients with mild to moderate renal impairment (creatinine clearance of 20 – 60 mL/min) is 20 mg olmesartan medoxomil once daily, owing to limited experience of higher dosages in this patient group. The use of Sevikar in patients with severe renal impairment (creatinine clearance < 20 mL/min) is not recommended (see 4.4, 5.2).

Monitoring of potassium levels and creatinine is advised in patients with moderate renal impairment.

Hepatic impairment

Sevikar should be used with caution in patients with mild to moderate hepatic impairment (see sections 4.4, 5.2).

In patients with moderate hepatic impairment, an initial dose of 10 mg olmesartan medoxomil once daily is recommended and the maximum dose should not exceed 20 mg once daily. Close monitoring of blood pressure and renal function is advised in hepatically-impaired patients who are already receiving diuretics and/or other antihypertensive agents. There is no experience of olmesartan medoxomil in patients with severe hepatic impairment.

As with all calcium antagonists, amlodipine's half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. Sevikar should therefore be administered with caution in these patients. The pharmacokinetics of amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose and titrated slowly in patients with impaired liver function. Use of Sevikar in patients with severe hepatic impairment is contraindicated (see section 4.3).

Paediatric population

The safety and efficacy of Sevikar in children and adolescents below 18 years has not been established. No data are available.

Method of administration:

The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed and should be taken at the same time each day.

4.3. Contraindications

Hypersensitivity to the active substances, to dihydropyridine derivatives or to any of the excipients listed in section 6.1.

Second and third trimesters of pregnancy (see sections 4.4 and 4.6).

Severe hepatic insufficiency and biliary obstruction (see section 5.2).

The concomitant use of Sevikar with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m2) (see sections 4.5 and 5.1).

Due to the component amlodipine Sevikar is also contraindicated in patients with:

- severe hypotension.

- shock (including cardiogenic shock).

- obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis).

- haemodynamically unstable heart failure after acute myocardial infarction

4.4. Special warnings and precautions for use

Patients with hypovolaemia or sodium depletion:

Symptomatic hypotension may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting, especially after the first dose. Correction of this condition prior to administration of Sevikar or close medical supervision at the start of the treatment is recommended.

Other conditions with stimulation of the renin-angiotensin-aldosterone system:

In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system, such as angiotensin II receptor antagonists, has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure.

Renovascular hypertension:

There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.

Renal impairment and kidney transplantation:

When Sevikar is used in patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. Use of Sevikar 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 Sevikar in patients with a recent kidney transplant or in patients with end-stage renal impairment (i.e. creatinine clearance < 12 mL/min).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS):

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Hepatic impairment:

Exposure to amlodipine and olmesartan medoxomil is increased in patients with hepatic impairment (see section 5.2). Care should be taken when Sevikar is administered in patients with mild to moderate hepatic impairment. In moderately impaired patients, the dose of olmesartan medoxomil should not exceed 20 mg (see section 4.2). In patients with impaired hepatic function, amlodipine should be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Use of Sevikar in patients with severe hepatic impairment is contraindicated (see section 4.3).

Hyperkalaemia:

As with other angiotensin II antagonists and ACE inhibitors, hyperkalaemia may occur during treatment, especially in the presence of renal impairment and/or heart failure (see section 4.5). Close monitoring of serum potassium levels in at-risk patients is recommended.

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (heparin, etc.) should be undertaken with caution and with frequent monitoring of potassium levels.

Lithium:

As with other angiotensin II receptor antagonists, the concomitant use of Sevikar and lithium is not recommended (see section 4.5).

Aortic or mitral valve stenosis; obstructive hypertrophic cardiomyopathy:

Due to the amlodipine component of Sevikar, as with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.

Primary aldosteronism:

Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of Sevikar is not recommended in such patients.

Heart failure:

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or death.

Patients with heart failure should be treated with caution. In a long-term, placebo controlled study of amlodipine in patients with severe heart failure (NYHA III and IV), the reported incidence of pulmonary oedema was higher in the amlodipine group than in the placebo group (see section 5.1). Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.

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.

Intestinal angioedema:

Intestinal angioedema has been reported in patients treated with angiotensin II receptor antagonists, [including olmesartan medoxomil] (see section 4.8). These patients presented with abdominal pain, nausea, vomiting and diarrhoea. Symptoms resolved after discontinuation of angiotensin II receptor antagonists. If intestinal angioedema is diagnosed, olmesartan medoxomil should be discontinued and appropriate monitoring should be initiated until complete resolution of symptoms has occurred.

Ethnic differences:

As with all other angiotensin II antagonists, the blood pressure lowering effect of Sevikar can be somewhat less in black patients than in non-black patients, possibly because of a higher prevalence of low-renin status in the black hypertensive population.

Elderly:

In the elderly, increase of the dosage should take place with care (see section 5.2).

Pregnancy:

Angiotensin II antagonists should not be initiated during pregnancy. Unless continued angiotensin II antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Other:

As with any antihypertensive agent, excessive blood pressure decrease in patients with ischaemic heart disease or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke.

This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially 'sodium-free'.

4.5. Interaction with other medicinal products and other forms of interaction

Potential interactions related to the Sevikar combination:

To be taken into account with concomitant use

Other antihypertensive agents:

The blood pressure lowering effect of Sevikar can be increased by concomitant use of other antihypertensive medicinal products (e.g. alpha blockers, diuretics).

Potential interactions related to the olmesartan medoxomil component of Sevikar:

Concomitant use not recommended

ACE-inhibitors, angiotensin II receptor blockers or aliskiren:

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).

Medicinal products affecting potassium levels:

Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels (e.g. heparin, ACE inhibitors) may lead to increases in serum potassium (see section 4.4). If medicinal products which affect potassium levels are to be prescribed in combination with Sevikar, monitoring of serum potassium levels is recommended.

Lithium:

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors and, rarely, with angiotensin II antagonists. Therefore concomitant use of Sevikar and lithium is not recommended (see section 4.4). If concomitant use of Sevikar and lithium proves necessary, careful monitoring of serum lithium levels is recommended.

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products (NSAIDs) including selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs:

When angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of worsening of renal function and may lead to an increase in serum potassium. Therefore monitoring of renal function at the beginning of such concomitant therapy is recommended, as well as adequate hydration of the patient.

Bile acid sequestering agent colesevelam:

Concurrent administration of the bile acid sequestering agent colesevelam hydrochloride reduces the systemic exposure and peak plasma concentration of olmesartan and reduces t1/2. Administration of olmesartan medoxomil at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect. Administering olmesartan medoxomil at least 4 hours before the colesevelam hydrochloride dose should be considered (see section 5.2).

Additional information

After treatment with antacid (aluminium magnesium hydroxide), a modest reduction in bioavailability of olmesartan was observed.

Olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin or the pharmacokinetics of digoxin. Coadministration of olmesartan medoxomil with pravastatin had no clinically relevant effects on the pharmacokinetics of either component in healthy subjects.

Olmesartan had no clinically relevant inhibitory effects on human cytochrome P450 enzymes 1A1/2, 2A6, 2C8/9, 2C19, 2D6, 2E1 and 3A4 in vitro, and had no or minimal inducing effects on rat cytochrome P450 activities. No clinically relevant interactions between olmesartan and medicinal products metabolised by the above cytochrome P450 enzymes are expected.

Potential interactions related to the amlodipine component of Sevikar:

Effects of other medicinal products on amlodipine

CYP3A4 inhibitors:

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure. The clinical translation of these PK variations may be more pronounced in the elderly. There is an increased risk of hypotension. Close observation of patients is recommended and dose adjustment may thus be required.

CYP3A4 inducers:

Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary. Therefore, blood pressure should be monitored and dose regulation considered both during and after concomitant medication particularly with strong CYP3A4 inducers (e.g. rifampicin, hypericum perforatum).

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.

Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Effects of amlodipine on other medicinal products

The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other antihypertensive agents.

In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin or warfarin.

Simvastatin: Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

Tacrolimus: There is a risk of increased tacrolimus blood levels when co-administered with amlodipine. In order to avoid toxicity of tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.

Mechanistic Target of Rapamycin (mTOR) Inhibitors: mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of mTOR inhibitors.

Cyclosporine: In a prospective study in renal transplant patients, an average 40% increase in trough cyclosporine levels was observed when used concomitantly with amlodipine. The co-administration of Sevikar with cyclosporine may increase exposure to cyclosporine. Monitor trough cyclosporine levels during concomitant use and cyclosporine dose reductions should be made as necessary.

4.6. Fertility, pregnancy and lactation

Pregnancy (see section 4.3)

There are no data about the use of Sevikar in pregnant patients. Animal reproductive toxicity studies with Sevikar have not been performed.

Olmesartan medoxomil (active ingredient of Sevikar)

The use of angiotensin II antagonists is not recommended during the first trimester of pregnancy (see section 4.4). The use of angiotensin II antagonists is contraindicated during the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with angiotensin II antagonists, similar risks may exist for this class of drugs. Unless continued angiotensin II antagonists therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II antagonists therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See section 5.3).

Should exposure to angiotensin II antagonists have occurred from the second trimester on, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken angiotensin II antagonists should be closely observed for hypotension (see sections 4.3 and 4.4).

Amlodipine (active ingredient of Sevikar)

Data on a limited number of exposed pregnancies do not indicate that amlodipine or other calcium receptor antagonists have a harmful effect on the health of the fetus. However, there may be a risk of prolonged delivery.

As a consequence, Sevikar is not recommended during the first trimester of pregnancy and is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4).

Breastfeeding

Olmesartan is excreted into the milk of lactating rats. However, it is not known whether olmesartan passes into human milk.

Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3 – 7%, with a maximum of 15%. The effect of amlodipine on infants is unknown.

During breast-feeding, Sevikar is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Fertility

Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Sevikar can have minor or moderate influence on the ability to drive and use machines.

Dizziness, headache, nausea or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair the ability to react. Caution is recommended especially at the start of treatment.

4.8. Undesirable effects

Sevikar:

The most commonly reported adverse reactions during treatment with Sevikar are peripheral oedema (11.3%), headache (5.3%) and dizziness (4.5%).

Adverse reactions from Sevikar in clinical trials, post-authorisation safety studies and spontaneous reporting are summarised in the below table as well as adverse reactions from the individual components olmesartan medoxomil and amlodipine based on the known safety profile of these substances.

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),

not known (cannot be estimated from the available data)

MedDRA System Organ Class

Adverse reactions

Frequency

Olmesartan/Amlodipine combination

Olmesartan

Amlodipine

Blood and lymphatic system disorders

Leukocytopenia

Very rare

Thrombocytopenia

Uncommon

Very rare

Immune system disorders

Allergic reaction /Drug hypersensitivity

Rare

Very rare

Anaphylactic reaction

Uncommon

Metabolism and nutrition disorders

Hyperglycaemia

Very rare

Hyperkalaemia

Uncommon

Rare

Hypertriglyceridaemia

Common

Hyperuricaemia

Common

Psychiatric disorders

Confusion

Rare

Depression

Uncommon

Insomnia

Uncommon

Irritability

Uncommon

Libido decreased

Uncommon

Mood changes (including anxiety)

Uncommon

Nervous system disorders

Dizziness

Common

Common

Common

Dysgeusia

Uncommon

Headache

Common

Common

Common (especially at the beginning of treatment)

Hypertonia

Very rare

Hypoaesthesia

Uncommon

Uncommon

Lethargy

Uncommon

Paraesthesia

Uncommon

Uncommon

Peripheral neuropathy

Very rare

Postural dizziness

Uncommon

Sleep disorder

Uncommon

Somnolence

Common

Syncope

Rare

Uncommon

Tremor

Uncommon

Extrapyramidal disorder

Not known

Eye disorders

Visual disturbance (including diplopia)

Common

Ear and labyrinth disorders

Tinnitus

Uncommon

Vertigo

Uncommon

Uncommon

Cardiac disorders

Angina pectoris

Uncommon

Uncommon (incl. aggravation of angina pectoris)

Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation)

Uncommon

Myocardial infarction

Very rare

Palpitations

Uncommon

Common

Tachycardia

Uncommon

Vascular disorders

Hypotension

Uncommon

Rare

Uncommon

Orthostatic hypotension

Uncommon

Flushing

Rare

Common

Vasculitis

Very rare

Respiratory, thoracic and mediastinal disorders

Bronchitis

Common

Cough

Uncommon

Common

Uncommon

Dyspnoea

Uncommon

Common

Pharyngitis

Common

Rhinitis

Common

Uncommon

Gastrointestinal disorders

Abdominal pain

Common

Common

Altered bowel habits (including diarrhoea and constipation)

Common

Constipation

Uncommon

Diarrhoea

Uncommon

Common

Dry mouth

Uncommon

Uncommon

Dyspepsia

Uncommon

Common

Common

Gastritis

Very rare

Gastroenteritis

Common

Gingival hyperplasia

Very rare

Nausea

Uncommon

Common

Common

Pancreatitis

Very rare

Upper abdominal pain

Uncommon

Vomiting

Uncommon

Uncommon

Uncommon

Intestinal angioedema (see section 4.4)

Rare

Sprue-like enteropathy (see section 4.4)

Very rare

Hepatobiliary disorders

Hepatic enzymes increased

Common

Very rare (mostly consistent with cholestasis)

Hepatitis

Very rare

Jaundice

Very rare

Autoimmune hepatitis*

Not known

Skin and subcutaneous tissue disorders

Alopecia

Uncommon

Angioneurotic oedema

Rare

Very rare

Allergic dermatitis

Uncommon

Erythema multiforme

Very rare

Exanthema

Uncommon

Uncommon

Exfoliative dermatitis

Very rare

Hyperhydrosis

Uncommon

Photosensitivity

Very rare

Pruritus

Uncommon

Uncommon

Purpura

Uncommon

Quincke oedema

Very rare

Rash

Uncommon

Uncommon

Uncommon

Skin discoloration

Uncommon

Stevens-Johnson syndrome

Very rare

Toxic Epidermal Necrolysis

Not known

Urticaria

Rare

Uncommon

Uncommon

Musculoskeletal and connective tissue disorders

Ankle swelling

Common

Arthralgia

Uncommon

Arthritis

Common

Back pain

Uncommon

Common

Uncommon

Muscle spasm

Uncommon

Rare

Common

Myalgia

Uncommon

Uncommon

Pain in extremity

Uncommon

Skeletal pain

Common

Renal and urinary disorders

Acute renal failure

Rare

Haematuria

Common

Increased urinary frequency

Uncommon

Micturition disorder

Uncommon

Nocturia

Uncommon

Pollakiuria

Uncommon

Renal insufficiency

Rare

Urinary tract infection

Common

Reproductive system and breast disorders

Erectile dysfunction/impotence

Uncommon

Uncommon

Gynecomastia

Uncommon

General disorders and administration site conditions

Asthenia

Uncommon

Uncommon

Common

Chest pain

Common

Uncommon

Face oedema

Rare

Uncommon

Fatigue

Common

Common

Common

Influenza-like symptoms

Common

Lethargy

Rare

Malaise

Uncommon

Uncommon

Oedema

Common

Very common

Pain

Common

Uncommon

Peripheral oedema

Common

Common

Pitting oedema

Common

Investigations

Blood creatinine increased

Uncommon

Rare

Blood creatine phosphokinase increased

Common

Blood potassium decreased

Uncommon

Blood urea increased

Common

Blood uric acid increased

Uncommon

Gamma glutamyl transferase increased

Uncommon

Weight decrease

Uncommon

Weight increase

Uncommon

*Cases of autoimmune hepatitis with a latency of few months to years have been reported post-marketing, that were reversible after the withdrawal of olmesartan.

Single cases of rhabdomyolysis have been reported in temporal association with the intake of angiotensin II receptor blockers. Single cases of extrapyramidal syndrome have been reported in patients treated with amlodipine.

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms:

There is no experience of overdose with Sevikar. The most likely effects of olmesartan medoxomil overdosage are hypotension and tachycardia; bradycardia could be encountered if parasympathetic (vagal) stimulation occurred. Amlodipine overdosage can be expected to lead to excessive peripheral vasodilatation with marked hypotension and possibly a reflex tachycardia. Marked and potentially prolonged systemic hypotension up to and including shock with fatal outcome has been reported.

Non-cardiogenic pulmonary oedema has rarely been reported as a consequence of amlodipine overdose that may manifest with a delayed onset (24-48 hours post-ingestion) and require ventilatory support. Early resuscitative measures (including fluid overload) to maintain perfusion and cardiac output may be precipitating factors.

Treatment:

If intake is recent, gastric lavage may be considered. In healthy subjects, the administration of activated charcoal immediately or up to 2 hours after ingestion of amlodipine has been shown to reduce substantially the absorption of amlodipine.

Clinically significant hypotension due to an overdose of Sevikar requires active support of the cardiovascular system, including close monitoring of heart and lung function, elevation of the extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade.

Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit. The dialysability of olmesartan is unknown.