Monograph: |
Indoramin Hydrochloride). A white or almost white powder. It exhibits polymorphism. Slightly soluble in water; sparingly soluble in alcohol; very slightly soluble in ether; soluble in methyl alcohol. A 2% suspension in water has a pH of 4.0 to 5.5. Protect from light.
Adverse Effects, Treatment, and Precautions
The most common adverse effects in patients receiving indoramin are sedation and dizziness; dry mouth, nasal congestion, headache, fatigue, depression, weight gain (almost certainly due to fluid retention), and failure of ejaculation may also occur. Tachycardia does not seem to be a problem with therapeutic doses but orthostatic hypotension may occur and may produce syncope. Extrapyramidal disturbances have been reported.
After overdosage, coma, convulsions, and hypotension may occur; hypothermia has been reported in animals. In acute poisoning appropriate symptomatic and supportive care should be given; if the patient presents within 1 hour, activated charcoal may be considered.
Indoramin should be avoided in patients with heart failure; it has been recommended that incipient heart failure should be controlled before giving indoramin. Caution should be observed in patients with hepatic or renal impairment, a history of depression, epilepsy, or Parkinson's disease. Elderly patients may respond to lower doses.
Because indoramin can cause drowsiness care should be taken in patients who drive or operate machinery.
Effects on mental function.
Sleep disturbances and vivid dreams were reported during a study in hypertensive patients when indoramin was added to therapy with a thiazide diuretic and a beta blocker.
Overdosage.
A 43-year-old woman with a long history of heavy alcohol intake died after taking 100 tablets of indoramin 25 mg. The main clinical features were deep sedation, respiratory depression, hypotension, and convulsions. Although the hypotension was satisfactorily controlled the CNS effects were resistant to treatment and proved fatal. Other clinical features included areflexia, metabolic acidosis, tachycardia, and later bradyarrhythmias.
Interactions
The hypotensive effects of indoramin may be enhanced by diuretics and other antihypertensives. It has been reported that the ingestion of alcohol can increase the rate and extent of absorption and the sedative effects of indoramin and that indoramin should not be given to patients already receiving MAOIs.
Alcohol.
In a study1 in 9 healthy subjects alcohol 500 mg/kg significantly enhanced plasma-indoramin concentrations following an oral dose of 50 mg. The effect was most marked in the early period, corresponding to the absorptive phase. The mean maximum plasma-indoramin concentration was increased from 15.0 to 23.7 nanograms/mL by alcohol; the area under the concentration/time curve was increased by 25%. Alcohol did not affect the pharmacokinetics of intravenous indoramin. The results suggest that alcohol increases indoramin bioavailability either by enhancing absorption or reducing first-pass metabolism. The combination was more sedative than either drug alone.
Pharmacokinetics
Indoramin is readily absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism. It is reported to be about 90% bound to plasma proteins. It has a half-life of about 5 hours which is reported to be prolonged in elderly patients. It is extensively metabolised and is excreted mainly as metabolites in the urine and faeces. There is evidence to suggest that some metabolites may have some alpha-adrenoceptor blocking activity.
The elderly.
The plasma half-life of indoramin in 5 healthy elderly subjects following a single oral dose ranged from 6.6 to 32.8 hours with a mean of 14.7 hours. The increased half-life may have been caused by reduced clearance in elderly patients.
Uses and Administration
Indoramin is a selective and competitive alpha1-adrenoceptor blocker with actions similar to those of prazosin; it is also reported to have membrane-stabilising properties and to be a competitive antagonist at histamine H1 and 5-hydroxytryptamine receptors. Indoramin is used in the management of hypertension, and in benign prostatic hyperplasia to relieve symptoms of urinary obstruction. It has also been used in the prophylactic treatment of migraine.
Indoramin is given by mouth as the hydrochloride, but doses are usually expressed in terms of the base. Indoramin hydrochloride 11.0 mg is equivalent to about 10 mg of indoramin.
In hypertension, the initial dose is 25 mg twice daily, increased in steps of 25 or 50 mg at intervals of 2 weeks to a maximum of 200 mg daily in 2 or 3 divided doses.
In benign prostatic hyperplasia, the initial dose is 20 mg twice daily, increased if necessary by 20 mg at 2-week intervals, to a maximum of 100 mg daily in divided doses.
Lower doses may be required in the elderly.
Migraine.
Propranolol is probably the most well-established drug for prophylaxis of migraine. Many other drugs have been used including indoramin. In a double-blind study, indoramin in a dose of 25 mg twice daily was reported to be as effective as dihydroergotamine mesilate in reducing the frequency of migraine attacks.
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