Rilmenidine

Rilmenidine

Systematic (IUPAC) name
N-(dicyclopropylmethyl)-4,5-dihydro-1,3-oxazol-2-amine
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	?
Routes	Oral
Pharmacokinetic data
Protein binding	7%
Metabolism	Minimal
Half-life	8 hours
Excretion	Renal, unchanged
Identifiers
CAS number	54187-04-1 N
ATC code	C02AC06
PubChem	CID 68712
ChemSpider	61963 Y
UNII	P67IM25ID8 Y
ChEMBL	CHEMBL289480 Y
Chemical data
Formula	C10H16N2O
Mol. mass	180.247 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C10H16N2O/c1-2-7(1)9(8-3-4-8)12-10-11-5-6-13-10/h7-9H,1-6H2,(H,11,12) Y Key:CQXADFVORZEARL-UHFFFAOYSA-N Y
N (what is this?)  (verify)

Rilmenidine is a prescription medication for the treatment of hypertension.^[1] It is marketed under the brand names HYPERIUM and Tenaxum.

Form and composition

Each tablet contains 1.544 mg rilmenidine dihydrogen phosphate, an amount equivalent to 1.000 mg of rilmenidine base.

Mode of action

Rilmenidine, an oxazoline compound with antihypertensive properties, acts on both medullary and peripheral vasomotor structures. Rilmenidine shows greater selectivity for imidazoline receptors than for cerebral alpha2-adrenergic receptors, distinguishing it from reference alpha2-agonists.

Indications

Hypertension.

Contraindications

Severe depression, severe renal failure (creatinine clearance <15 ml/min), as a precaution in the absence of currently available studies.

Warning

Therapy should never be interrupted suddenly; the dosage should be reduced gradually.

Precautions

• As with all antihypertensive agents, regular medical monitoring is required when rilmenidine is administered to patients with a recent history of cardiovascular disease (stroke, myocardial infarction).
• Alcohol consumption should be avoided during treatment.
• In patients with renal failure, no dosage adjustment is necessary if creatinine clearance is greater than 15 mL/min.
• In the absence of documented experiments in this area, rilmenidine is not recommended for prescription to children.
• Pregnancy: as with all new molecules, administration of rilmenidine should be avoided in pregnant women, although no teratogenic or embryotoxic effects have been observed in animal studies.
• Lactation: rilmenidine is excreted in breast milk, and its use is therefore not recommended during lactation.
• Effects on the ability to drive motor vehicles or operate machinery: double-blind, placebo-controlled studies have not shown rilmenidine to have any effect on alertness at therapeutic doses (1or 2 daily administrations of 1 mg). If these doses are exceeded, or if rilmenidine is combined with other drugs capable of reducing alertness, vehicle drivers or machine operators should be warned of the possibility of drowsiness.

Drug interactions

Combinations not recommended: combination with MAOIs is not recommended; combination with tricyclic antidepressants requires prudence, as the antihypertensive activity of rilmenidine may be partly antagonized.

Side effects

• At a dose of 1 mg given as a single daily administration during controlled trials, the incidence of side effects was comparable to that observed with placebo.
• At a dose of 2 mg per day of rilmenidine, controlled comparative studies versus clonidine (0.15 to 0.30 mg/day) or alpha2-methyldopa (500 to 1000 mg/day) demonstrated that the incidence of side effects was significantly lower with rilmenidine than with either clonidine or a-methyldopa.

Side-effects are rare, non-severe, and transient at therapeutic doses: asthenia, palpitations, insomnia, drowsiness, fatigue on exercise, epigastric pain, dryness of the mouth, diarrhea, skin rash; and exceptionally, cold extremities, postural hypotension, sexual disorders, anxiety, depression, pruritus, edema, cramps, nausea, constipation, hot flushes.

Dosage and route of administration

The recommended dosage is 1 tablet per day as a single morning administration. If results are not adequate after 1 month of treatment, the dosage may be increased to 2 tablets per day, given in divided doses (1 tablet morning and evening) before meals. As a result of its good clinical and biological acceptability, rilmenidine may be administered to both elderly and diabetic hypertensive patients. In patients with renal failure, no dosage adjustment is necessary in principle when the creatinine clearance is greater than 15 mL/min.

Treatment may be continued indefinitely.

Overdosage

No cases of massive absorption have been reported. Likely symptoms in such an eventuality would be marked hypotension and lowered alertness. In addition to gastric lavage, sympathomimetic agents may also required. Rilmenidine is only slightly dialysable.

References