ISMELIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ISMELIN (ISMELIN).
Guanethidine inhibits norepinephrine release from postganglionic sympathetic nerve terminals and depletes norepinephrine stores, leading to reduced sympathetic tone and vasodilation.
| Metabolism | Metabolized primarily by hepatic N-oxidation and N-dealkylation; metabolites are excreted renally. |
| Excretion | Primarily renal excretion of unchanged drug (40-50%) and metabolites; remainder is biliary/fecal. Exact percentages not well defined. |
| Half-life | Terminal half-life of 5-7 days; allows once-daily dosing. Clinical context: long half-life leads to cumulative effects and prolonged washout. |
| Protein binding | Less than 10% bound to plasma proteins. |
| Volume of Distribution | Approximately 0.03-0.06 L/kg; small Vd consistent with limited tissue distribution. |
| Bioavailability | Oral bioavailability variable, approximately 30-50% due to first-pass metabolism. |
| Onset of Action | Oral: 48-72 hours for initial hypotensive effect; maximal effect in 1-2 weeks. |
| Duration of Action | Up to 2-3 weeks after cessation due to long half-life and tissue binding; clinical effect persists beyond drug levels. |
Initiate at 10 mg orally twice daily; increase gradually by 10 mg increments every 1-2 weeks. Typical maintenance dose 25-50 mg twice daily; maximum 150 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 50%. GFR 15-29 mL/min: reduce dose by 75%. GFR <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | 0.2 mg/kg/day orally divided every 12 hours; titrate weekly by 0.2 mg/kg/day. Maximum 5 mg/kg/day or 150 mg/day. |
| Geriatric use | Initiate at 5 mg orally twice daily; increase by 5 mg increments every 1-2 weeks. Maximum 75 mg/day due to increased sensitivity and orthostatic hypotension risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ISMELIN (ISMELIN).
| Breastfeeding | Guanethidine is excreted in breast milk; the M/P ratio is unknown. Due to potential for adverse effects in the nursing infant, including hypotension and bradycardia, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | Ismelin (guanethidine) is contraindicated in pregnancy, particularly in the first trimester due to potential teratogenic effects. Animal studies have shown fetal abnormalities, and there are no adequate human studies. Risk cannot be excluded. |
| Fetal Monitoring |
■ FDA Black Box Warning
May cause severe orthostatic hypotension, syncope, and bradycardia. Use with caution in patients with cerebrovascular or coronary insufficiency.
| Serious Effects |
Absolute: Pheochromocytoma, concurrent use or recent use of MAOIs, catecholamine-depleting agents. Relative: Severe cerebrovascular insufficiency, myocardial infarction, asthma, renal impairment.
| Precautions | Orthostatic hypotension is common and may be severe; patients should avoid sudden posture changes. Use cautiously with beta-blockers, MAOIs, and volatile anesthetics. May exacerbate bronchial asthma. Discontinue 2 weeks before elective surgery due to interaction with anesthetics. Do not use with MAOIs or pheochromocytoma. |
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| Monitor maternal blood pressure, heart rate, and signs of hypotension. Fetal monitoring should include heart rate and growth parameters if inadvertent exposure occurs, especially in later trimesters. |
| Fertility Effects | Guanethidine may cause inhibition of ejaculation in males and has been associated with decreased libido. In females, effects on fertility are not well-established but may include menstrual irregularities. |