Hypertension Knowledge Centre
Centrally Acting Drugs
Tolerability and safety of moxonidine
Cumulative exposure to moxonidine worldwide is currently over one million patient years.69 The clinical safety and adverse events profiles have been well established in approximately 100 clinical trials and a large post-marketing surveillance report.70 Moxonidine has been generally very well tolerated in controlled clinical studies, either as monotherapy or adjunctive therapy. A low incidence of treatmentemergent adverse events has been reported, most of which were mild or transient, and adverse events only occasionally lead to discontinuation of treatment.
In studies versus active comparators, monotherapy with moxonidine was at least as well tolerated as monotherapy with agents from all the main antihypertensive drug classes.70 Figure 22 shows tolerability results from an 8-week randomised, double-blind, placebo-controlled study versus enalapril, which used the highest recommended daily dose of moxonidine (0.6mg daily).24 The most common adverse event with moxonidine was dry mouth, which affected 18% of patients.
Figure 22: Treatment-emergent adverse events affecting ≥4% in patients receiving monotherapy with moxonidine 0.6mg/day, enalapril 20mg/day, or placebo in an 8-week randomised, double-blind, multicentre trial. Adapted from24
Moxonidine is well tolerated in older patients, with a similar profile of adverse events to that seen in younger patients.70 Adverse events with moxonidine when used in combination with enalapril, amlodipine or HCTZ in randomised, double-blind, multicentre trials were characteristic of those of the individual component drugs.19,30,34
Long-term tolerability
Moxonidine was considered to be well or very well tolerated in 137/141 patients (97%) who received moxonidine for 12 months in an openlabel study.28 During the 12 months of the study, the only treatmentemergent adverse events with an overall incidence greater than 2% were dry mouth and tiredness, which were mostly reported during the early weeks of therapy (figure 23). After three months of treatment, the only adverse event with an incidence greater than 2% was dry mouth.
Figure 23: Treatment-emergent adverse events affecting ≥2% of patients in long-term open-label studies of moxonidine. Adapted from28
Post-marketing data
Tolerability data are available for the use of moxonidine in 91,170 hypertensive patients (>18,500 patient-years), about two-thirds of whom received monotherapy.70 Over 7,000 patients were assessed for six months or more, and over 15,000 patients (16.5%) had co-existing diabetes. Adverse events were reported in 9.4% of patients, the most common adverse event being dry mouth (3.6%). Treatment was discontinued by 1.8% of patients because of adverse events.
Cautions/contraindications
Please see National Prescribing Information or Summary of Product Characteristics (SmPC), as licence details may vary between countries.
The Master SmPC for moxonidine lists the following as contraindications:
- known hypersensitivity to any of the components of the product
- sick sinus syndrome
- bradycardia (resting heart rate <50 beats/minute)
Studies have not revealed rebound hypertension with moxonidine, but it would be advisable to withdraw treatment gradually over two weeks. When stopping combined therapy with a beta-blocker, the beta-blocker should be stopped a few days before stopping moxonidine.
On renally impaired patients, the dosage should be titrated according to the individual requirements. In patients with moderate-to-severe renal impairment the starting dose is 0.2mg/day. If necessary and well tolerated the dose can be increased to 0.4mg/day. The same dosage recommendations also apply to patients undergoing haemodialysis. Caution should be exercised when prescribing to pregnant women. Lactating women should be advised not to breast feed while on moxonidine, or they should stop treatment with the drug.
Safety
Toxicology studies provided no indication that moxonidine has any teratogenic, mutagenic, or carcinogenic potential. There was no evidence of serious adverse effects on organs or organ systems, and no evidence of deleterious effects on perinatal or postnatal growth and development.15