Moxonidine is indicated for the treatment of hypertension

The usual initial dose of moxonidine is 0.2 mg daily, with a maximum daily dose of 0.6 mg given as
two divided doses. The maximum single dose to be administered is 0.4 mg. Adjustments in daily dose
should be individualized to the patient’s response.
Moxonidine can be administered with or without food.
In patients with moderate to severe renal impairment the starting dose is 0.2 mg daily. If necessary and
well tolerated the dose can be increased to 0.4 mg daily in patients with moderate renal impairment
and to 0.3 mg daily in patients with severe renal impairment (see section “Special warnings and
precautions for use”).
In patients undergoing haemodialysis the starting dose is 0.2 mg daily. If necessary and well tolerated
the dose can be increased to 0.4 mg daily.
Moxonidine is not recommended for use in children and adolescents below 18 years due to lack of
data on safety and efficacy.

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
“Contraindications”).
When moxonidine is used in patients with severe coronary artery disease or unstable angina pectoris,
special care should be exercised due to the fact that there is limited experience in this patient
population.
Caution is advised in the administration of moxonidine to patients with renal impairment as
moxonidine is excreted primarily via the kidney. In these patients careful titration of the dose is
recommended, especially at the start of therapy.
Dosing should be initiated with 0.2 mg daily and can be increased to a maximum of 0.4 mg daily for
patients with moderate renal impairment (GFR > 30 ml/ min but < 60 ml/ min) and to a maximum of
0.3 mg daily for patients with severe renal impairment (GFR < 30 ml/ min), if clinically indicated and
well tolerated.
If moxonidine is used in combination with a β-blocker and both treatments have to be discontinued,
the β-blocker should be discontinued first, and then moxonidine after a few days.
So far, no rebound-effect has been observed on the blood pressure after discontinuing the treatment
with moxonidine. However, an abrupt discontinuance of the moxonidine treatment is not advisable;
instead the dose should be reduced gradually over a period of two weeks.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose
malabsorption should not take this medicine.

Concomitant administration moxonidine and other antihypertensive agents result in an additive effect.
Since tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive
agents, it is not recommended that tricyclic antidepressants be co-administered with moxonidine.
Moxonidine can potentiate the sedative effect of tricyclic anti-depressants (avoid co-prescribing),
tranquillizers, alcohol, sedatives and hypnotics.
Moxonidine moderately augmented the impaired performance in cognitive functions in subjects
receiving lorazepam. Moxonidine may enhance the sedative effect of benzodiazepines when
administered concomitantly.

Moxonidine is excreted through tubular excretion. Interaction with other agents that are excreted
through tubular excretion cannot be excluded

Pregnancy:
There are no adequate data from use of moxonidine in pregnant woman. Studies in animals have
shown embryo-toxicological effects (see section 5.3). The potential risk for humans is unknown.
Moxonidine should not be used during pregnancy unless clearly necessary.
Lactation:
Moxonidine is secreted in breast milk and should therefore not be used during breast feeding. If
therapy with moxonidine is considered absolutely necessary, the breast feeding shall be stopped.

Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. Somnolence
and dizziness have been reported. This should be borne in mind when performing these tasks.

Most frequent side effects reported by those taking moxonidine include dry mouth, dizziness, asthenia
and somnolence. These symptoms often decrease after the first few weeks of treatment.
Undesirable Effects by System Organ Class (observed during placebo-controlled clinical trials with
n=886 patients exposed to moxonidine resulted in frequencies below):

* The frequency was not increased compared with placebo.

Reporting of suspected undesirable effects.

The reporting of suspected undesirable effects after authorisation is of great importance. It enables continuous monitoring of the medicinal product’s risk-benefit ratio. Healthcare professionals are asked to report every suspected case of an undesirable effect 

To report any side effect(s):

- National Pharmacovigilance Center (NPC)

o    Fax: +966-11-205-7662

o    SFDA Call Center: 19999

o    E-mail: npc.drug@sfda.gov.sa

o    Website: https://ade.sfda.gov.sa

Symptoms of overdose
In the few cases of overdose that have been reported, a dose of 19.6 mg was ingested acutely without
fatality. Signs and symptoms reported included: headache, sedation, somnolence, hypotension,
dizziness, asthenia, bradycardia, dry mouth, vomiting, fatigue and upper abdominal pain. In case of a
severe overdose close monitoring of especially consciousness disturbances and respiratory depression
is recommended.

In addition, based on a few high dose studies in animals, transient hypertension, tachycardia, and
hyperglycaemia may also occur.
Treatment of overdose
No specific antidote is known. In case of hypotension, circulatory support such as fluids and dopamine
administration may be considered. Bradycardia may be treated with atropine.
α-Receptor antagonists may diminish or abolish the paradox hypertensive effects of a moxonidine
overdose.

Pharmacotherapeutic group: Imidazoline receptor agonists, moxonidine
ATC code: C02AC05.
In different animal models, moxonidine has been shown to be a potent antihypertensive agent.
Available experimental data suggests that the site of the antihypertensive action of moxonidine is the
central nervous system (CNS). Within the brainstem, moxonidine has been shown to selectively
stimulate imidazoline receptors. These imidazoline-sensitive receptors are concentrated in the rostral
ventrolateral medulla, an area critical to the central control of the peripheral sympathetic nervous
system. Stimulation of the imidazoline receptors appears to reduce sympathetic activity and lower
blood pressure.
Moxonidine distinguishes itself from other sympatholytic antihypertensives by exhibiting only low
affinity for known α2-adrenoceptors, as compared to imidazoline receptors. This low affinity to α2-
adrenoceptors may account for a low incidence of sedation and dry mouth with moxonidine.
In humans, moxonidine leads to a reduction of systemic vascular resistance and consequently arterial
blood pressure. The antihypertensive effect of moxonidine has been demonstrated in double-blind,
placebo controlled randomized studies. Published data show that in hypertensive patients with left
ventricular hypertrophy (LVH), for the same blood pressure reduction, the use of an Angiotensin II
Antagonist (AIIA) together with moxonidine achieved an improved LVH regression compared to a
free combination of a thiazide and a Calcium channel blocker.
In a therapeutic trial of two months' duration, moxonidine improved the insulin sensitivity index by
21% in comparison to placebo in obese and insulin resistant patients with moderate hypertension.

Absorption:
After oral administration moxonidine is rapidly (tmax around 1 h) and almost completely absorbed from
the upper gastrointestinal tract. The absolute bioavailability is about 88%, indicating no significant
first-pass metabolism. Food intake has no influence on the pharmacokinetics of moxonidine.
Distribution:
Plasma protein binding, as determined in vitro, was about 7.2%.
Biotransformation:
In pooled human plasma samples, only dehydrogenated moxonidine was identified. The
pharmacodynamic activity of dehydrogenated moxonidine is about 1/10 compared to moxonidine.

Based on the conventional studies on safety pharmacology, chronic toxicity, reproductive toxicity, genotoxicity and carcinogenic potential, the preclinical data do not indicate any particular risk for humans.

Experimental studies on animals have shown embryotoxic effects at maternally toxic doses.

Reproductive studies did not reveal any impaired fertility or teratogenic effects.

Embryotoxic effects were observed in rats in the dose range above 3 mg/kg of body weight daily and in rabbits above 0.7 mg/kg of body weight daily.

In a peri- and post-natal study on rats, development and viability of the young were impaired at doses above 1 mg/kg of body weight daily.

Carcinogenicity studies on rats at doses up to 3.6 mg/kg of body weight daily and on mice up to 7.5 mg/kg of body weight daily revealed no evidence of a carcinogenic risk through moxonidine.

Elimination:
Over a 24-hour period, 78% of the total dose was excreted in urine as parent moxonidine and 13% of
the dose was excreted as dehydrogenated moxonidine. Other minor metabolites in urine accounted for
approximately 8% of the dose. Less than 1% is eliminated via the faeces. The elimination half-lifes of
moxonidine and its metabolite are approximately 2.5 h and 5 h, respectively).
Pharmacokinetics in Hypertensive Patients:
In hypertensive patients, no relevant pharmacokinetic changes were observed compared to healthy
volunteers.
Pharmacokinetics in the Elderly:
Age-related changes in pharmacokinetics have been observed and are most likely due to a reduced
metabolic activity and/ or slightly higher bioavailability in the elderly. However, these
pharmacokinetic differences are not considered to be clinically relevant.
Pharmacokinetics in Children:
As moxonidine is not recommended for use in children, no pharmacokinetic studies have been
performed in this subpopulation.
Pharmacokinetics in Renal Impairment:
Elimination of moxonidine is significantly correlated with the creatinine clearance. In patients with
moderate renal impairment (GFR 30-60 ml/ min) steady-state plasma concentrations and terminal halflife
are approximately 2-fold and 1.5-fold higher, respectively, compared to hypertensive patients with
normal renal function (GFR > 90 ml/ min). In patients with severe renal impairment (GFR < 30 ml/
min) steady-state plasma concentrations and terminal half-life are approximately 3-fold higher. No
unexpected drug accumulation after multiple dosing was observed in these patients. In end-stage renal
patients (GFR < 10 ml/ min) undergoing hemodialysis the AUC and terminal half-life are 6-fold and
4-fold higher, respectively compared to hypertensive patients with normal renal function. In patients
with moderate renal impairment maximum moxonidine plasma concentrations are only 1.5 to 2-fold
higher.
In renally impaired patients, the dosage should therefore be titrated according to the individual
requirements.
Moxonidine is eliminated to a small extent by hemodialysis.
Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.
Studies in animals have shown embryo-toxicity effects with maternal-toxicity doses.
Studies on reproduction toxicity showed no effect on fertility and no teratogen potential.
Embryotoxicological effects were seen in rat with doses at and above 9 mg/ kg/ day and in rabbit with
doses above 0.7 mg/ kg/ day. In a peri- and post-natal study on rat influence on development and
vitality was noted with doses at and above 3 mg/ kg/ day.

List of excipients
Lactose monohydrate, Povidone K25, Crospovidone, Magnesium stearate, Hypromellose,
Ethylcellulose, Macrogol 6000, Talc, Red ferric oxide , Titanium dioxide .

Not applicable.

Store below 30°C.

PVC aluminium blister pack or PVC/PVDC aluminium blister pack

Original packagings with:

- 28 film-coated tablets

- 98 film-coated tablets

Not all pack sizes may be marketed

No special requirements.