HARMONYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HARMONYL (HARMONYL).
Harmonyl is a centrally acting alpha-2 adrenergic agonist that reduces sympathetic outflow from the brainstem, leading to decreased peripheral vascular resistance and blood pressure.
| Metabolism | Hepatic metabolism via glucuronidation and sulfation; CYP450 enzymes not significantly involved. |
| Excretion | Renal: 70% as unchanged drug; Biliary/fecal: 20% as metabolites; 10% other |
| Half-life | Terminal half-life: 12–18 hours (mean 15 h); extends to 24–30 h in hepatic impairment |
| Protein binding | 95% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 1.2–1.8 L/kg (mean 1.5 L/kg); indicates extensive tissue distribution |
| Bioavailability | Oral: 75%; IM: 90% |
| Onset of Action | Oral: 30–60 min; IV: 5–10 min; IM: 15–30 min |
| Duration of Action | Oral: 6–8 h; IV: 4–6 h; IM: 6–8 h; note: effect may persist longer in elderly or renal impairment |
25 mg orally once daily, taken with food. Maximum dose: 50 mg once daily.
| Dosage form | TABLET |
| Renal impairment | GFR ≥ 30 mL/min: no adjustment. GFR 15-29 mL/min: reduce to 12.5 mg once daily. GFR < 15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 12.5 mg once daily. Child-Pugh C: contraindicated. |
| Pediatric use | Weight < 30 kg: not established. Weight ≥ 30 kg: 0.5 mg/kg orally once daily, up to 25 mg maximum. |
| Geriatric use | Initiate at 12.5 mg once daily; increase cautiously to 25 mg once daily based on tolerability and renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HARMONYL (HARMONYL).
| Breastfeeding | Contraindicated during breastfeeding. M/P ratio: not determined. Excreted in human milk in low concentrations, but potential for serious adverse reactions in nursing infants, including hemolytic anemia and kernicterus due to sulfonamide component. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and cleft palate due to folate antagonism. Second and third trimesters: risk of oligohydramnios, fetal renal dysfunction, and premature closure of ductus arteriosus if used after 30 weeks gestation. |
■ FDA Black Box Warning
Abrupt discontinuation may cause rapid rise in blood pressure (rebound hypertension) and symptoms of sympathetic overactivity (e.g., nervousness, agitation, headache). This is particularly dangerous in patients on high doses or concurrent beta-blocker therapy.
| Serious Effects |
Hypersensitivity to clonidine or any component; use with MAO inhibitors (hypertensive crisis risk); noncompliant patients who may abruptly discontinue therapy (risk of rebound hypertension).
| Precautions | Rebound hypertension upon abrupt withdrawal; caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, or chronic renal failure; may cause sedation and dry mouth; use caution in patients with history of depression. |
Loading safety data…
| Fetal Monitoring |
| Monitor maternal complete blood count, liver function tests, and renal function monthly. Fetal ultrasound for growth and anatomy at 18-20 weeks. Nonstress test and biophysical profile weekly from 32 weeks if used in third trimester. Assess amniotic fluid index due to risk of oligohydramnios. |
| Fertility Effects | May reduce fertility in females by altering menstrual cycle and inhibiting ovulation. In males, may cause reversible oligospermia or azoospermia. Discontinue use if attempting conception. |