Consumer medicine information

1. Why am I taking OLMESARTAN HCTZ-WGR?

OLMESARTAN HCTZ-WGR contains the active ingredients olmesartan and hydrochlorothiazide (HCTZ). OLMESARTAN HCTZ-WGR is used to treat high blood pressure (hypertension).
For more information, see Section 1. Why am I taking OLMESARTAN HCTZ-WGR? in the full CMI.

2. What should I know before I take OLMESARTAN HCTZ-WGR?

Do not take if you have ever had an allergic reaction to OLMESARTAN HCTZ-WGR 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 take OLMESARTAN HCTZ-WGR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with OLMESARTAN HCTZ-WGR 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 take OLMESARTAN HCTZ-WGR?

• The usual dose is one tablet taken once a day. Your doctor will tell you how much medicine you will need to take each day, depending on your condition and if you are taking any other medicines.

• Follow all directions given to you by your doctor or pharmacist carefully.

5. What should I know while taking OLMESARTAN HCTZ-WGR?

6. Are there any side effects?

There are a number of side effects associated with OLMESARTAN HCTZ-WGR. It is important to be aware of them so that you can identify any symptoms if they occur.
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/hydrochlorothiazide.

2 Qualitative and Quantitative Composition

Olmesartan HCTZ-WGR 20/12.5 film coated tablets contain 20 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide.
Olmesartan HCTZ-WGR 40/12.5 film coated tablets contain 40 mg of olmesartan medoxomil and 12.5 mg of hydrochlorothiazide.
Olmesartan HCTZ-WGR 40/25 film coated tablets contain 40 mg of olmesartan medoxomil and 25 mg of hydrochlorothiazide.
Excipients with known effect. Sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Olmesartan HCTZ-WGR 20/12.5 Yellow film coated, round, biconvex tablets debossed with '346' on one side and 'L' on other side.
Olmesartan HCTZ-WGR 40/12.5. Yellow film coated, oval shape, biconvex tablets debossed with 'L347' on one side and plain on other side.
Olmesartan HCTZ-WGR 40/25. Yellow film coated, oval shape, biconvex tablets debossed with 'L348' on one side and plain on other side.

4 Clinical Particulars

4.9 Overdose

No specific information is available on the effects or treatment of Olmesartan HCTZ-WGR overdosage. The patient should be closely monitored, and the treatment should be symptomatic and supportive. Management depends upon the time since ingestion and the severity of the symptoms. Activated charcoal may be useful in the treatment of overdosage. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacements given quickly.
The most likely manifestations of olmesartan medoxomil overdosage are expected to be hypotension and tachycardia; bradycardia might also occur. Overdosage with HCTZ is associated with electrolyte depletion (hypokalaemia, hypochloraemia) and dehydration resulting from excessive diuresis. The most common signs and symptoms of overdosage are nausea and somnolence. Hypokalaemia may result in muscle spasm and/or accentuate cardiac arrhythmias associated with the concomitant use of digitalis glycosides or certain anti-arrhythmic drugs.
No information is available regarding the dialysability of olmesartan or HCTZ.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Olmesartan medoxomil. 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 the intestine and kidney of a mutagenic susceptible mouse (MutaMouse) and for clastogenicity in mouse bone marrow (micronucleus test) at oral doses of up to 2,000 mg/kg/day. Olmesartan not tested in this mouse model. On balance, the weight-of-evidence indicates that olmesartan medoxomil does not pose a genotoxic risk at clinically relevant doses.
HCTZ. HCTZ was negative in several different assays of gene mutation and chromosomal aberration. However, positive test results were obtained in the in vitro CHO sister chromatid exchange (clastogenicity) assay and the mouse lymphoma (mutagenicity) assay at HCTZ concentrations of 43-1,200 microgram/mL.
Olmesartan medoxomil and HCTZ. Olmesartan medoxomil/HCTZ in a ratio of 20:12.5 was negative in the bacterial reverse mutation test up to the maximum recommended plate concentration for the standard assays. As expected, positive clastogenicity responses were observed with either drug or the combination (40:12.5, 20:12.5, 10:12.5) in Chinese hamster lung cells but no synergistic clastogenicity was observed. However, the combination (20:12.5) was negative in the in vivo mouse micronucleus test at oral doses (1,935/1,209 mg/kg) that were likely to achieve high relative systemic exposure (> 33-700-fold based on AUC) to both components.
Carcinogenicity. The carcinogenic potential of olmesartan medoxomil and HCTZ in combination has not been investigated.
Olmesartan medoxomil was not carcinogenic when administered by dietary administration to rats for up to 2 years. The highest dose tested (2,000 mg/kg/day) corresponded to a relative systemic exposure to olmesartan that was about 30 times that anticipated at the maximum recommended human dose (MRHD) of 40 mg/day (based on AUC). 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 1,000 mg/kg/day (about 11 times anticipated clinical exposure to olmesartan at the MRHD, based on AUC in Hras2), revealed no evidence of a carcinogenic effect of olmesartan medoxomil.
Two-year feeding studies in mice and rats showed no evidence of carcinogenic potential for HCTZ in female mice at doses up to approximately 600 mg/kg/day, or in male and female rats at doses up to approximately 100 mg/kg/day. There was equivocal evidence for hepatocarcinogenicity in male mice treated with HCTZ at approximately 600 mg/kg/day.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Olmesartan medoxomil is a prodrug, hydrolysed to olmesartan during absorption from the gastrointestinal tract. Olmesartan is a selective AT₁ subtype angiotensin II receptor antagonist. HCTZ is a thiazide diuretic.
Olmesartan medoxomil is a white to light yellowish-white powder or crystalline powder with a molecular weight of 558.59. It is practically insoluble in water and sparingly soluble in methanol.
HCTZ is a white, or almost white, crystalline powder, with a molecular weight of 297.7. HCTZ is very slightly soluble in water, soluble in acetone, sparingly soluble in alcohol. It dissolves in dilute solutions of alkali hydroxides.
Chemical structure. Olmesartan medoxomil.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSOLMMED.gif Chemical name: 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.
Molecular formula: C₂₉H₃₀N₆O₆.
CAS number. 144689-63-4.
Chemical structure. Hydrochlorothiazide.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSHYDROC.gif Chemical name: 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1dioxide.
Molecular formula: C₇H₈ClN₃O₄S₂.
CAS number. 58-93-5.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

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