Consumer medicine information

Moxotens Tablets

Moxonidine

BRAND INFORMATION

Brand name

Moxotens

Active ingredient

Moxonidine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Moxotens Tablets.

What is in this leaflet

This leaflet answers some common questions about Moxotens.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Moxotens against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medication. You may want to read it again.

What Moxotens is used for

Moxotens lowers high blood pressure, which is sometimes called hypertension.

Everyone has blood pressure. This pressure helps to move your blood around your body. Your blood pressure may change at different times of the day. You have hypertension when your blood pressure stays higher than normal, even when you are calm or relaxed.

There are usually no symptoms of hypertension. The only way of knowing if you have hypertension is to have your blood pressure checked regularly. If high blood pressure is not treated it can lead to serious health problems, including stroke, heart disease and kidney failure.

Ask your doctor if you have any questions about why it has been prescribed for you. Your doctor may have prescribed Moxotens for another use.

This medicine is only available with a doctor's prescription.

This medicine is not addictive.

Before you take Moxotens

When you must not take it

Do not take Moxotens if you have an allergy to:

  • any medicine containing moxonidine
  • any of the ingredients listed at the end of this leaflet

Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty breathing.

Do not take this medicine if you are pregnant or think you may be pregnant.

Do not breastfeed if you are taking this medicine. Moxotens passes into breast milk. Your doctor will discuss the possible risks and benefits of taking Moxotens when breastfeeding.

Do not give Moxotens to a child under the age of 16 years. Safety and effectiveness in children younger than 16 years have not been established.

Do not take Moxotens if you:

  • are aged 75 years or more
  • have heart problems such as heart failure or abnormal rhythm
  • have severe kidney disease

Do not take it after the expiry date (EXP) printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have any allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have, or have had, any of the following medical conditions:

  • kidney problems
  • heart problems
  • angio-oedema, which is unusual swelling of the face, lips or tongue
  • leg pains or cramps caused by poor blood circulation
  • Raynaud's disease, where your fingers go pale and blue and are painful in the cold
  • Parkinson's disease, a disease of the nerves which causes uncontrolled shaking and stiffness
  • epilepsy
  • glaucoma, a disease of increased pressure in the eye
  • depression

Tell your doctor or pharmacist if you are pregnant, intend to become pregnant or are breastfeeding. Your doctor or pharmacist can discuss the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you take Moxotens.

Taking other medicines

Tell your doctor if you are already taking medicines to lower your blood pressure. These medicines can have a combined effect when used with Moxotens to reduce blood pressure and your doctor may need to adjust the dose you have to take.

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may affect the way other medicines work. These include:

  • some medicines used to treat depression called "tricyclic" medicines (such as imipramine and amitriptyline)
  • sleeping tablets or other medicines which make you feel drowsy

These medicines may be affected by Moxotens, or may affect how well it works. You may need to use different amounts of your medicine, or take different medicines.

Your doctor or pharmacist has more information on medicines to be careful with or to avoid while taking Moxotens.

How to take Moxotens

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Your doctor or pharmacist will tell you how many tablets to take each day.

The usual starting dose of Moxotens is one 0.2 mg (200 microgram) tablet once per day.

Depending on how your blood pressure responds your dosage may be increased by your doctor to 0.4 mg (400 micrograms) after 2 weeks. After a further 2 weeks your doctor may increase your dosage to 0.6 mg per day (600 micrograms). You should not take 0.6 mg as one dose, it should be taken as a divided dose.

Ask your doctor how to divide your daily dose.

How to take it

Swallow the tablets whole with a full glass of water or another liquid.

Do not chew the tablets.

When to take it

Take Moxotens at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

It does not matter if you take this medicine with or without food.

How long to take it

Continue taking your medicine for as long as your doctor tells you. The medicine helps control your condition, but it does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

If there is still a long time to go before your next dose, take it as soon as you remember, and then go back to taking it as you would normally.

Do not take two doses within 6 hours of each other. Do not take a double dose to make up for the dose that you missed. This may increase the chance of getting an unwanted side effect.

If you have trouble remembering when to take your medicine, ask your pharmacist for advice.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (13 11 26), or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much Moxotens. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If possible, show the doctor the pack of tablets.

While you are using Moxotens

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Moxotens.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon that you are taking this medicine.

If you become pregnant while you are taking this medicine, tell your doctor or pharmacist immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

Keep all of your doctor's appointments so that your progress can be checked.

Make sure you drink enough water during exercise and hot weather when you are taking Moxotens, especially if you sweat a lot. If you do not drink enough water while taking Moxotens, you may faint or feel light-headed or sick. This is because your body does not have enough fluid and your blood pressure is too low.

Tell your doctor if you have excessive vomiting and/or diarrhoea while taking Moxotens. This can also mean that you are losing too much water and your blood pressure may become too low.

Things you must not do

Do not use this medicine to treat any other complaints unless your doctor or pharmacist tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Do not stop taking Moxotens abruptly, or change the dosage, without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how Moxotens affects you. Moxotens may cause drowsiness, dizziness or light-headedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

You should avoid drinking alcohol when taking Moxotens. The effect of taking alcohol with Moxotens has not been studied. Ask your doctor for advice.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Moxotens.

It helps most people with high blood pressure, but it may have unwanted side effects in a few people. All medicines have some unwanted side effects. Sometimes they are serious, but most of the time they are not. You may need medical attention if you get some of the side-effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • dry mouth
  • headache
  • lack of energy
  • dizziness
  • drowsiness
  • feeling sick, nausea
  • problems sleeping
  • skin flushing
  • anxiety

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • severe allergic skin reactions (rash, itching, inflamed or reddened skin)
  • swelling of the limbs

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • angio-oedema (unusual swelling of the face, eyes, lips, inside the nose, mouth or throat)
  • shortness of breath, breathing or swallowing difficulties.

The above list includes very serious side effects. You may need urgent medical attention. These side effects are rare.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some consumers.

After using Moxotens

Storage

Keep your tablets in the original pack until it is time to take them. If you take the tablets out of the box they may not keep well.

Keep the medicine in a cool dry place where the temperature stays below 25°C.

Do not store it in the bathroom, near the sink, or on a window sill. Do not leave it in the car. Heat and damp can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and- a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or the medicine has passed its expiry date, ask your pharmacist what to do with any that are left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

Moxotens 0.2 mg (200 micrograms) tablets - Pale pink coloured round shaped tablet debossed with MX2 on one side and plain on another side.. Packs of 30 tablets.

Moxotens 0.4 mg (400 micrograms) tablets - Dull brick red coloured round shaped tablet debossed with MX4 on one side and plain on another side.. Packs of 30 tablets.

Ingredients

Moxotens contains either 0.2 mg (200 micrograms) or 0.4 mg (400 micrograms) of moxonidine as the active ingredient.

It also contains:

  • lactose monohydrate
  • povidone
  • crospovidone
  • magnesium stearate
  • OPADRY complete film coating system 03F540200 PINK (PI 111786).
  • OPADRY complete film coating system 03F540201 PINK (PI 111784)

This medicine contains sugars as lactose.

Moxotens tablets do not contain tartrazine or any other azo dyes.

Supplier

Moxotens is supplied in Australia by:

Arrotex Pharmaceuticals Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121

® Registered Trademark

This leaflet was prepared September 2022.

Australian Registration Number(s)

0.2 mg tablets: AUST R 300132

0.4 mg tablets: AUST R 300129

Published by MIMS November 2022

BRAND INFORMATION

Brand name

Moxotens

Active ingredient

Moxonidine

Schedule

S4

 

1 Name of Medicine

Moxonidine.

2 Qualitative and Quantitative Composition

Moxonidine is a white to almost white powder with a melting point of 197 - 205°C. Moxonidine is very slightly soluble in water, sparingly soluble in methanol.

200 microgram.

Each tablet contains 200 microgram moxonidine.

400 microgram.

Each tablet contains 400 microgram moxonidine.
List of excipients with known effect: contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablet, film coated.

Moxotens 200 microgram tablets.

Pale pink, coloured round shaped tablet debossed with MX2 on one side and plain on another side.

Moxotens 400 microgram tablets.

Dull brick red coloured round shaped tablets debossed with MX4 on one side and plan on another side.

4 Clinical Particulars

4.1 Therapeutic Indications

Moxotens is indicated for the treatment of hypertension.

4.2 Dose and Method of Administration

Treatment should be started with 200 microgram Moxotens in the morning. The dose may be titrated after two weeks to 400 microgram given as one dose or as divided doses (morning and evening) until a satisfactory response is achieved. If the response is still unsatisfactory after a further 2 weeks treatment, the dosage can be increased up to a maximum of 600 microgram in divided doses (morning and evening).
A single daily dose of 400 microgram and a divided daily dose of 600 microgram of Moxotens should not be exceeded.
Moxotens may be taken with or without food.

4.3 Contraindications

Hypersensitivity to any of the ingredients of this product.
Heart failure (NYHA Class I - IV).
Patients aged 75 years or older.
Bradycardia (HR < 50 beats/minute) or severe bradyarrhythmia, including sick sinus syndrome, or second or third degree atrioventricular (AV) block.
Malignant arrhythmias.
Severe renal impairment (GFR < 30 mL/min, serum creatinine concentration > 160 micromol/L).

4.4 Special Warnings and Precautions for Use

Renal impairment.

In patients with moderate renal impairment (GFR 30 - 60 mL/min), the single dose should not exceed 200 microgram and the daily dose should not exceed 400 microgram of moxonidine.

Use in the elderly.

See Section 4.3 Contraindications; Section 5.2 Pharmacokinetic Properties, Pharmacokinetics in the elderly.

Paediatric use.

Moxotens should not be given to children below the age of 16 years as insufficient therapeutic experience exists in this group.

Effects on laboratory tests.

No data available.

Cessation of combination therapy with beta-blockers.

Abrupt cessation of combination therapy with Moxotens and a beta-blocker may result in rebound hypertension. If combination therapy with Moxotens and a beta-blocker is to be ceased, the beta-blocker should be stopped first and then Moxotens stopped after a few days have elapsed. During cessation of therapy blood pressure should be regularly monitored.

Angioneurotic oedema.

As with other centrally acting antihypertensives, Moxotens should be used with caution in patients with a history of angioneurotic oedema, severe coronary artery disease and unstable angina.
Cases of varying degrees of AV block have been reported in the post-marketing setting in patients undergoing moxonidine treatment. Based on these case reports, the causative role of moxonidine in delaying atrioventricular conduction cannot be completely ruled out. Therefore, caution is recommended when treating patients with a possible predisposition to developing an AV block.
When moxonidine is used in patients with 1st degree AV block, special care should be exercised to avoid bradycardia. Moxonidine must not be used in higher degree AV blocks (see Section 4.3 Contraindications).
In patients with moderate renal impairment (GFR > 30 - < 60 mL/min, serum creatinine > 105 - < 160 micromol/L), the hypotensive effect of Moxotens should be closely monitored, especially at the start of treatment (see Section 4.2 Dose and Method of Administration).
Moxotens should not be used because of lack of experience in cases of intermittent claudication, Raynaud's Disease, Parkinson's Disease, epileptic disorders, glaucoma, and depression.
Due to lack of therapeutic experience, the use of Moxotens concomitantly with alcohol or tricyclic antidepressants should be avoided.
In limited studies, no rebound effect of the blood pressure after sudden discontinuation of moxonidine treatment has been detected. Nevertheless, it is advised not to interrupt the intake of Moxotens abruptly. Moxotens should be withdrawn gradually over a period of days.
Due to the presence of lactose in Moxotens tablets, patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concurrent administration of other antihypertensive agents enhances the hypotensive effect of Moxotens.
The effect of sedatives and hypnotics may be intensified by Moxotens. The sedative effect of benzodiazepines can be enhanced by concurrent administration of Moxotens.
Moxonidine moderately augmented the impaired performance in cognitive functions in subjects receiving lorazepam.
Since tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive agents, it is not recommended that tricyclic antidepressants be co-administered with moxonidine.
In healthy volunteers, no pharmacokinetic interactions have been observed with glibenclamide or digoxin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Moxonidine did not affect fertility of rats at oral doses up to 6.4 mg/kg/day (15-64 times the clinical exposure at 0.3 mg BID, based on plasma moxonidine concentration).
(Category B3)
Moxonidine was not teratogenic in rats. It caused abortions, increased embryofoetal losses, and/or delayed foetal development at high oral doses (≥ 9 mg/kg/day in rats and 4.9 mg/kg/day in rabbits), associated with maternal toxicity. No adverse effects on embryofoetal development were seen at 2 mg/kg/day in rats and 0.6 mg/kg/day in rabbits. Exposures at the no effect dose were 24 (rat, based on AUC) and 22 (rabbit, based on dose adjusted for body surface area) times the clinical exposure at the maximum recommended clinical dose (0.3 mg BID).
There is inadequate data in pregnant women or women of childbearing age, and as such moxonidine should not be used during pregnancy unless the benefit clearly justifies the possible risk to the foetus.
 Oral administration of moxonidine to rats from late pregnancy until weaning was associated with maternotoxicity, reduced pup weight and viability, and delayed pup development at ≥ 3 mg/kg/day, with no effects at 1 mg/kg/day (approximately 12 times the clinical exposure at 0.3 mg BID, based on AUC).
Studies in humans have shown that moxonidine passed from the maternal blood stream to breast milk. As the effect on the newborn infant is unknown, moxonidine should not be used by nursing mothers, unless the benefits clearly justify the possible risks to the infants.

4.7 Effects on Ability to Drive and Use Machines

Based on its pharmacodynamic properties, moxonidine is unlikely to affect the ability to drive or operate machinery. However, it should be taken into account that occasionally dizziness or weariness may occur during treatment of hypertension.

4.8 Adverse Effects (Undesirable Effects)

Moxonidine has been evaluated for safety in over 4000 subjects worldwide, including more than 1200 patients treated for more than 6 months and over 800 patients treated for 1 year or longer. Most adverse events were of mild or moderate severity and did not require discontinuation of therapy.
In placebo-controlled clinical trials, 4.7% of patients treated with moxonidine discontinued therapy due to clinical adverse experiences, compared to 2.5% discontinuations among placebo-treated patients. Table 1 lists adverse events that occurred at an incidence of 1% or more among moxonidine-treated patients who participated in placebo-controlled trials of 6 to 8 weeks' duration, using doses of 200 microgram to 0.8 mg daily.

Laboratory test finding.

In controlled clinical trials, clinically important changes in standard laboratory parameters possibly associated with administration of moxonidine were rarely observed and occurred at rates comparable to those seen with placebo.

Post-marketing adverse events.

Common (≥ 1/100 and < 1/10): dry mouth, headache, dizziness, nausea, sleep disturbance, somnolence, asthenia, vasodilatation, anxiety.
Uncommon (≥ 1/1000 and < 1/100): sedation, insomnia, skin rash, urticaria, pruritus.
Rare (≥ 1/10,000 and < 1/1000): hypotension, postural hypotension.
Very rare (< 1/10,000): angioedema.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Oral dosages up to 2.0 mg/day have been tolerated without the occurrence of serious adverse events. The following case of accidental overdose with moxonidine by a 2 year old child has been reported: The child ingested an unknown quantity of moxonidine. The maximum dosage possibly ingested was 14 mg. The child had the following symptoms: sedation, coma, hypotension, miosis and dyspnoea. Gastric Lavage, glucose infusion, mechanically assisted ventilation and rest resulted in the complete disappearance of the symptoms in 11 hours.
Because of the pharmacodynamic properties of moxonidine, the following symptoms can be expected in adults: sedation, hypotension, orthostatic dysregulation, bradycardia, dry mouth. In rare cases emesis and paradoxical hypertension may occur. No specific treatment is known. Phentolamine (Regitine) may, depending on the dose, reverse part of the symptoms of moxonidine overdose. Measures to support blood circulation are recommended.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

In different animal models, moxonidine has been shown to be a relatively potent antihypertensive agent. Available experimental data suggest that the site of the antihypertensive action of moxonidine is the central nervous system (CNS). Moxonidine has been shown to bind to I1-imidazoline receptors and to a lesser extent α2-adrenoreceptors. The therapeutic action of moxonidine appears to result from interaction with I1 and α2-receptors located within the rostral ventrolateral medulla, leading to a reduced activity of sympathetic nerves.
Moxonidine differs from other available centrally acting antihypertensives by exhibiting only low affinity to central α2-adrenoceptors compared to I1-imidazoline receptors; α2-adrenoceptors are considered the molecular target via which sedation and dry mouth, the most common side effects of centrally acting antihypertensives, are mediated. In humans, moxonidine leads to a reduction of systemic vascular resistance and consequently in arterial blood pressure.

Clinical trials.

The antihypertensive effects of moxonidine were demonstrated in three placebo- and reference-controlled pivotal trials, studying dosages of 0.2 to 0.6 mg once daily in patients with mild to moderate hypertension (office diastolic blood pressure 95 - 110 mmHg; 24 hour ambulatory diastolic blood pressure ≥ 85 mmHg). The studies allowed direct comparison of moxonidine to a reference agent (enalapril) at equipotent doses, analysis of peak and trough effects, and (in pooled data) an evaluation of the dose response relationship. In all, 464 patients were included, of whom 152 were randomized to moxonidine. All studies were double-blind, placebo and reference-controlled, prospectively randomized, parallel group comparisons, with a 4 week placebo run-in period followed by 8 weeks double-blind treatment.
The first study compared 200 microgram moxonidine with 5 mg enalapril and placebo once daily. The intent-to-treat patient population comprised 169 patients evaluable for office blood pressure and 152 for ABPM. The mean placebo-subtracted differences in office systolic/diastolic blood pressure at trough from baseline to week 8 were -3.40/-4.65 mmHg for moxonidine. The reduction for diastolic blood pressure was statistically significant versus placebo (p < 0.001) and not different from enalapril. The difference in systolic blood pressure did not differ statistically from placebo. The overall incidence of adverse events of moxonidine (27.8%) was similar to enalapril (26.7%) and placebo (22.8%) in this trial.
In the second study of similar design, 400 microgram moxonidine was compared with 10 mg enalapril and placebo once daily. A total of 139 patients were included in the intent-to-treat sample for office blood pressure and 108 patients for ABPM. Moxonidine reduced office systolic and diastolic blood pressures at trough highly statistically significantly by 13.08/7.01 mmHg (placebo-corrected; p < 0.001 for both) and was equivalent to enalapril. Similar results were obtained with the 24 hour, daytime and night-time ABPM values. The 24 hour effects were maintained over the dosing interval with a trough to peak ratio of approximately 70%. Treatment emergent adverse events were reported in 36.6% of the moxonidine patients, in 31.9% of the enalapril patients and in 28.9% with placebo.
In the third pivotal study of similar design, 0.6 mg moxonidine was compared with 20 mg enalapril and placebo once daily. The intent-to-treat population consisted of 154 patients for office blood pressure measurements and 130 for ABPM. Office systolic and diastolic blood pressures were markedly and statistically significantly reduced by moxonidine by 21.53/10.45 mmHg (placebo-corrected; p < 0.001 for both) in comparison to placebo and did not differ from enalapril. Mean 24-hour ABPM was statistically reduced versus placebo for both diastolic and systolic blood pressures as well. Adverse events were recorded for 43.1% of patients in the moxonidine group in comparison to 32.1% in the enalapril group and 22.6% with placebo.
The main efficacy results for the primary and secondary parameters can be taken from the Table 2.
The combination of hydrochlorothiazide and moxonidine was evaluated in a further placebo-controlled, double-blind and prospectively randomized trial. The study comprised a total of 161 randomized patients: 37 received moxonidine 400 microgram, 40 received hydrochlorothiazide 25 mg, 42 received the combination 0.4/25 mg and 41 received placebo, all once daily. Sitting systolic and diastolic blood pressures at trough after eight weeks treatment were statistically significantly reduced for all active treatment arms versus placebo. Furthermore, the difference of the combination for sitting diastolic blood pressure was statistically significant in favour of the combination for both monotherapies. The incidence of treatment emergent adverse events did not differ significantly between groups: 32.5% with moxonidine, 25% with HCT, 30% with the combination and 23% with placebo. See Table 3.

5.2 Pharmacokinetic Properties

Absorption.

In humans, about 90% of an oral dose of moxonidine is absorbed; it is not subject to first-pass metabolism and its bioavailability is 88%. Food intake does not interfere with moxonidine pharmacokinetics. The maximum plasma levels of moxonidine are reached 30 - 180 minutes after the intake of a film-coated tablet.

Distribution.

Only about 10% of moxonidine is bound to plasma proteins (Vdss=1.8±0.4 L/kg).

Metabolism.

Moxonidine is 10 - 20% metabolised, mainly to 4,5-dehydromoxonidine and to a guanidine derivative by opening of the imidazoline ring. The hypotensive effect of 4,5- dehydromoxonidine is only 1/10, and that of the guanidine derivative is less than 1/100 of that of moxonidine.

Excretion.

Moxonidine and its metabolites are eliminated almost entirely via the kidneys. More than 90% of the dose is eliminated via the kidneys in the first 24 hours after administration, while only about 1% is eliminated via the faeces. The cumulative renal excretion of unchanged moxonidine is about 50 - 75%.
The mean plasma elimination half-life of moxonidine is 2.2 - 2.3 hours, and renal elimination half-life is 2.6 - 2.8 hours. Although moxonidine has a relatively short half-life it should be administered no more frequently than twice daily.

Pharmacokinetics in the elderly.

In older patients, the exposure (AUC) to moxonidine increased by approximately 50% following a single dose and at steady state, therefore lower doses of moxonidine should be used for the treatment of hypertension (see Section 4.3 Contraindications).

Pharmacokinetics in renal impairment.

In moderately impaired renal function (GFR 30 - 60 mL/min), AUC increases by 85% and clearance decreased to 52%. In such patients the hypotensive effect of moxonidine should be closely monitored, especially at the start of treatment (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

Genotoxicity.

Moxonidine did not induce gene mutations in bacteria or mammalian cells in vitro. Nor did it induce chromosomal aberrations in human lymphocytes in vitro or in Chinese hamster bone marrow cells in vivo.

Carcinogenicity.

Carcinogenicity studies in rats and mice at oral doses of up to 3.6 mg/kg (rat) and 7.4 mg/kg (mouse) did not reveal evidence of carcinogenic potential. Systematic exposures at the highest dose were approximately 3 (rats, based on plasma moxonidine concentration) and 63 (mice, based on and dose adjusted for body surface area) times the clinical exposure at 0.3 mg BID.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each tablet includes the following excipients: lactose monohydrate, crospovidone, povidone, magnesium stearate, Opadry complete film coating system 03F540200 Pink (PI 111786) for 200 microgram strength and Opadry complete film coating system 03F540201 Pink (PI 111784) for 400 microgram strength.

6.2 Incompatibilities

Concurrent administration of other antihypertensive agents enhances the hypotensive effect of Moxotens.
The effect of sedatives and hypnotics may be intensified by Moxotens. The sedative effect of benzodiazepines can be enhanced by concurrent administration of Moxotens.
Moxonidine moderately augmented the impaired performance in cognitive functions in subjects receiving lorazepam.
Since tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive agents, it is not recommended that tricyclic antidepressants be co-administered with moxonidine.
In healthy volunteers, no pharmacokinetic interactions have been observed with glibenclamide or digoxin.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Moxotens tablets should be stored below 25°C. Protect from light. Protect from moisture.

6.5 Nature and Contents of Container

Supplied in blister pack as follows:

Moxotens 200 microgram tablets.

PVC/PVDC/Al blister pack of 7 tablets (sample), 10 tablets, 14 tablets, 28 tablets, 30 tablets, 56 tablets, 84 tablets and 98 tablets.

Moxotens 400 microgram tablets.

PVC/PVDC/Al blister pack of 7 tablets (sample), 10 tablets, 14 tablets, 28 tablets, 30 tablets, 56 tablets, 84 tablets and 98 tablets.
Not all pack sizes will be marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Chemical name: 4-chloro-N-(imidazolidin-2-ylidine)-6-methoxy-2-methyl-5-pyrimidinamine. C9H12ClN5O, MW: 241.7.

CAS number.

75438-57-2.

7 Medicine Schedule (Poisons Standard)

Schedule 4: Prescription Only Medicine.

Summary Table of Changes