INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo PHYSIOTENS 0,2 Film-coated tablets
PHYSIOTENS 0,3 Film-coated tablets
PHYSIOTENS 0,4 Film-coated tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

PHYSIOTENS 0,2 Film-coated tablets
PHYSIOTENS 0,3 Film-coated tablets
PHYSIOTENS 0,4 Film-coated tablets

COMPOSITION
Each film-coated tablet contains 0,2, 0,3 or 0,4 mg
moxonidine

PHARMACOLOGICAL CLASSIFICATION
A. 7.1.3 Other hypotensives.

PHARMACOLOGICAL ACTION
Pharmacodynamic properties
In different animal models moxonidine has been shown to have antihypertensive effects. Available experimental data suggest that the site of the antihypertensive action of moxonidine is the central nervous system. Within the brainstem, moxonidine has been shown to selectively interact with I1-imidazoline receptors. These imidazoline-sensitive receptors are concentrated in rostral ventrolateral medulla, an area critical to the central control of the peripheral sympathetic nervous system. The net effect of this interaction with the I1-imidazoline receptors appears to result in a reduced activity of sympathetic nerves (demonstrated for cardiac, splanchnic and renal sympathetic nerves).
Moxonidine exhibits only low affinity to central alpha2-adrenoceptors.
In humans moxonidine leads to a reduction of systemic vascular resistance and consequently in arterial blood pressure.
Pharmacokinetic properties
Approximately 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. Moxonidine is 10 to 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. The maximum plasma levels of moxonidine are reached 30 to 180 minutes after intake of a film-coated tablet.
Only approximately 7% of moxonidine is bound to human plasma protein (Vdss = 1,8 + 0,4 L/kg). 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 to 70%.
The mean plasma elimination half-life of moxonidine is 2,2 to 2,3 hours, and the renal elimination half-life is 2,6 to 2,8 hours. The elimination half-life of the metabolites was in the order of 5 hours as measured by total radioactivity. The antihypertensive potency of the two main metabolites was less than 10% of the parent compound.
The pharmacokinetic properties of moxonidine in healthy elderly showed significantly increased tmax and AUC values. However, the differences were small and are unlikely to be clinically relevant.
In moderately impaired renal function (GFR 30 to 60 mL/min), steady state plasma concentrations of moxonidine are higher, but no accumulation occurs. In these patients the dosage should therefore be reduced according to individual requirements.

INDICATIONS
Mild to moderate essential hypertension.

CONTRA-INDICATIONS
Physiotens should not be used in cases of:
- history of angioneurotic oedema,
- hypersensitivity to any of the ingredients,
- sick sinus syndrome or sino-atrial block,
- 2nd or 3rd degree atrioventricular block,
- bradycardia (below 50 beats/minute at rest),
- malignant arrhythmia,
- severe heart failure,
- severe coronary artery disease or unstable angina,
- severe liver disease,
- severe renal dysfunction (GFR <30 mL/minute, serum creatinine concentration >160 micromol/L).

Physiotens should not be used because of lack of therapeutic experience in cases of:
- intermittent claudication,
- Raynaud’s disease,
- Parkinson’s disease,
- epileptic disorders,
- glaucoma,
- depression,
- pregnancy or lactation,
- children below 16 years of age.

WARNINGS
The use of Physiotens concomitantly with alcohol or tricyclic antidepressants should be avoided as safety and efficacy have not been demonstrated.
If Physiotens is used in combination with a beta-blocker and the treatment has to be stopped, the beta-blocker should be stopped first and then Physiotens after a few days have elapsed.
In patients with moderate renal dysfunction (GFR above 30 but below 60 mL/min, serum creatinine above 105 but below 160 micromol/L), the hypotensive effect of Physiotens should be closely monitored, especially at the start of treatment.
In limited studies no rebound effect of the blood pressure after sudden discontinuation of Physiotens treatment has been detected. Nevertheless, it is advised not to interrupt the intake of Physiotens abruptly. Physiotens should be withdrawn gradually over a period of two weeks.
No data are available to suggest that moxonidine adversely affects the ability to drive or operate machinery. However, as somnolence and dizziness have been reported, patients should be cautioned about their ability to undertake potentially hazardous tasks such as driving and operating machinery if so affected.

DOSAGE AND DIRECTIONS FOR USE
Treatment should be started with 0,2 mg of Physiotens in the morning. The dose may be titrated after three weeks to 0,4 mg, given as one dose or as divided doses (morning and evening) until a satisfactory response has been achieved.
A single dose of 0,4 mg of Physiotens or 0,2 mg twice daily (morning and evening) should not be exceeded.
In patients with moderate renal dysfunction (GFR above 30 mL/min, but below 60 mL/min), the single dose should not exceed 0,2 mg.
The tablets should be taken with liquid. As the intake of food has no influence on the pharmacokinetic properties of moxonidine, the tablets may be taken before, during, or after a meal.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Dry mouth is frequently observed at the start of treatment and headache, asthenia, dizziness, somnolence, sedation, nausea, sleep disturbances and vasodilatation may occur.
The frequency and intensity of these symptoms may decrease in the course of treatment.
Interactions
Concurrent administration of hydrochlorothiazide enhances the hypotensive effect of moxonidine.
The effect of sedatives and hypnotics may be intensified by moxonidine. The sedative effect of benzodiazepines can be enhanced by the concurrent administration of moxonidine.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Oral dosages up to 2,0 mg/day have been tolerated without the occurrence of serious adverse events.
Because of the pharmacodynamic properties of moxonidine, the following symptoms can be expected in adults: sedation, hypotension, orthostatic hypotension and dizziness, bradycardia, dry mouth. In rare cases emesis and paradoxical hypertension may occur.
Treatment is symptomatic and supportive.

IDENTIFICATION
Physiotens 0,2: Light pink, round, biconvex, film-coated tablets imprinted with “0.2”on one side.
Physiotens 0,3: Pale red, round, biconvex, film-coated tablets imprinted with “0.3”on one side.
Physiotens 0,4: Dull red, round, biconvex, film-coated tablets imprinted with “0.4”on one side.

PRESENTATION
Blisterpacks containing 28 and 56 tablets.

STORAGE INSTRUCTIONS
Store below 25°C.
Keep out of reach of children.

REGISTRATION NUMBER
Physiotens 0,2:         32/7.1.3/0139
Physiotens 0,3:         32/7.1.3/0140
Physiotens 0,4:         32/7.1.3/0141

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Schering (Pty) Ltd
(Reg No: 1964/09072/07)
106 Sixteenth Road
Randjespark
Midrand 1685
P O Box 5278
Halfway House 1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT
21 October 1998

Updated on this site: December 2000

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