Consumer medicine information

1. Why am I using SEVIKAR?

SEVIKAR contains the active ingredient olmesartan medoxomil and amlodipine besilate. SEVIKAR is used to treat high blood pressure.
For more information, see Section 1. Why am I using SEVIKAR? in the full CMI.

2. What should I know before I use SEVIKAR?

Do not use if you have ever had an allergic reaction to SEVIKAR or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use SEVIKAR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SEVIKAR and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SEVIKAR?

• Follow all directions given to you by your doctor or pharmacist carefully. Your doctor will tell you which SEVIKAR tablet you will need to take each day.

• Swallow SEVIKAR whole with a full glass of water.

• Take your tablets at the same time each day.

5. What should I know while using SEVIKAR?

6. Are there any side effects?

Common side effects may include dizziness, feeling light-headed, cough, headache, feeling nauseous, vomiting, diarrhoea, tiredness, 'flu-like' symptoms, sore throat, difficulty swallowing, back pain, swelling of the face or body and urinary infection.
Serious side effects may include swelling of the face, lips tongue or throat which causes difficulty swallowing or breathing and muscle pain.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Olmesartan medoxomil and amlodipine as besilate.

2 Qualitative and Quantitative Composition

Sevikar 20/5 contains 20 mg of olmesartan medoxomil and amlodipine 5 mg as besilate.
Sevikar 20/10 contains 20 mg of olmesartan medoxomil and amlodipine 10 mg as besilate.
Sevikar 40/5 contains 40 mg of olmesartan medoxomil and amlodipine 5 mg as besilate.
Sevikar 40/10 contains 40 mg of olmesartan medoxomil and amlodipine 10 mg as besilate.
Olmesartan medoxomil is a white to light yellowish-white powder or crystalline powder. It is practically insoluble in water and sparingly soluble in methanol.
Amlodipine besilate is a white crystalline powder, slightly soluble in water and sparingly soluble in ethanol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Sevikar 20/5 is a round tablet, approximately 6 mm in diameter, white in colour with C73 debossed on one side.
Sevikar 20/10 is a round tablet, approximately 8 mm in diameter, greyish-orange in colour with C74 debossed on one side. (Not currently available in Australia).
Sevikar 40/5 is a round tablet, approximately 8 mm in diameter, cream in colour with C75 debossed on one side.
Sevikar 40/10 is a round tablet, approximately 8 mm in diameter, brownish red in colour with C77 debossed on one side.

4 Clinical Particulars

4.9 Overdose

Symptoms. There is no experience of overdose in humans 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 (see following section).
Treatment. 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.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. No genotoxicity studies have been conducted with the olmesartan medoxomil/ amlodipine combination.
Both olmesartan medoxomil and olmesartan tested negative in the in vitro Syrian hamster embryo cell transformation assay and showed no evidence of genetic toxicity in the Ames (bacterial mutagenicity) test. However, both were shown to induce chromosomal aberrations in cultured cells in vitro (Chinese hamster lung) and tested positive for thymidine kinase mutations in the in vitro mouse lymphoma assay. Olmesartan medoxomil tested negative in vivo for mutations in intestinal and kidney cells from the transgenic mouse strain MutaMouse and for clastogenicity in mouse bone marrow (micronucleus test) at oral doses of up to 2000 mg/kg (olmesartan not tested).
Amlodipine did not induce gene mutation in bacteria and mouse lymphoma cells; nor did it induce chromosome aberrations in human lymphocytes or Chinese hamster V79 fibroblast (in vitro) and in mouse bone marrow cells (in vivo).
Carcinogenicity. There are no carcinogenicity studies with the olmesartan medoxomil/ amlodipine combination.
Olmesartan was not carcinogenic when administered by dietary administration to rats for up to 2 years. The highest dose tested (2000 mg/kg/day) was, on a mg/m² basis, about 480 times the maximum recommended human dose (MRHD) of 40 mg/day. Two carcinogenicity studies conducted in mice, a 6 month gavage study in the p53 knockout mouse and a 6 month dietary administration study in the Hras2 transgenic mouse, at doses of up to 1000 mg/kg/day (about 120 times the MRHD), revealed no evidence of a carcinogenic effect of olmesartan. Rats and mice treated with amlodipine maleate in the diet for up to two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg amlodipine/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on mg/m² basis, similar to the maximum recommended human dose [MRHD] of 10 mg amlodipine/day. For the rat, the highest dose was, on a mg/m² basis, about two and a half times the MRHD (calculations based on a 60 kg patient).

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Olmesartan medoxomil is chemically described as 2,3-dihydroxy-2-butenyl 4-(1-hydroxy- 1-methylethyl)-2-propyl-1-[p-(o-1H-tetrazol-5-ylphenyl) benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate. The empirical formula is C₂₉H₃₀N₆O₆ and its molecular weight is 558.59.
Amlodipine besilate is a racemic mixture and is chemically described as 3-ethyl-5-methyl-2- (2-aminoethoxymethyl)-4-(2-chlorophenyl)- 1,4-dihydro-6-methyl-3,5- pyridinedicarboxylate benzene sulphonate. The empirical formula is C₂₀H₂₅ClN₂O₅.C₆H₆O₃S and its molecular weight is 567.1.
Chemical structure. Olmesartan medoxomil has the following structural formula:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSOLMMED.gif Amlodipine besilate has the following structural formula:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSAMBESI.gif CAS number. The CAS Registry Number is 144689-63-4 (olmesartan medoxomil); 111470-99-6 (amlodipine besilate).

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/SEVIKAST.gif