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|Indication(s) & Dosage||
General considerations: Methyldopa is largely excreted by the kidney, and patients with impaired renal function may respond to smaller doses.
Withdrawal of Methyldopa (Aldomet) is followed by return of hypertension, usually within 48 hours. This is not complicated generally by an overshoot of blood pressure.
Therapy may be initiated in most patients already on treatment with other antihypertensive agents by terminating these antihypertensive medications gradually, as required. Following such previous antihypertensive therapy, Methyldopa should be limited to an initial dose of not more than 500 mg daily and increased as required at intervals of not less than two days.
When methyldopa is given to patients on other antihypertensives the dose of these agents may need to be adjusted to effect a smooth transition.
When 500mg of Methyldopa is added to 50mg or hydrochlorothiazide, the two agents may be given together once daily.
Many patients experience sedation for two or three days when therapy with Methyldopa (Aldomet) is started or when the dose is increased. When increasing the dosage, therefore, it may be desirable to increase the evening dose first.
Oral therapy â€“ Adults: Initial dosage: Usually 250mg two or three times a day for two days.
Adjustment: Usually adjusted at intervals of not less than two days, until an adequate response is obtained. The maximum recommended dosage is 3g.
Oral therapy â€“ Children: initial dose is based on 10mg/kg of bodyweight daily in 2-4 oral doses. The daily dosage is then increased or decreased until adequate response is achieved. The maximum dosage is 65mg/kg or 3.0g daily, whichever is less.
Use in the elderly: The initial dose in elderly patients should be kept as low as possible, not exceeding 250mg daily, an appropriate starting dose in the elderly would be 125mg b.d increasing slowly as required, but not to exceed a maximum daily dosage of 2g. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses.
|Administration||Should be taken with food. Take immediately after meals.
|Overdosage||Symptoms: Hypotension, sedation, bradycardia, dizziness, constipation or diarrhoea, flatus, nausea, vomiting. Management: Supportive and symptomatic. Can be removed by hemodialysis.|
|Contraindications||Phaeochromocytoma, active liver disease. Patients in whom previous methyldopa treatment resulted in liver abnormalities or direct Coombs' positive haemolytic anaemia.|
Acquired haemolytic anaemia has occurred rarely; should symptoms suggest anaemia, haemoglobin and/or haematocrit determinations should be made. If anaemia is confirmed, tests should be done for haemolysis. If haemolytic anaemia is present, 'Aldomet' should be discontinued. Stopping therapy, with or without giving a corticosteroid, has usually brought prompt remission. Rarely, however, deaths have occurred.
Some patients on continued therapy with methyldopa develop a positive Coombs test. From the reports of different investigators, the incidence averages between 10% and 20%. A positive Coombs test rarely develops in the first six months of therapy, and if it has not developed within 12 months, it is unlikely to do so later on continuing therapy. Development is also dose-related, the lowest incidence occurring in patients receiving 1 g or less of methyldopa per day. The test becomes negative usually within weeks or months of stopping methyldopa.
Prior knowledge of a positive Coombs reaction will aid in evaluating a cross-match for transfusion. If a patient with a positive Coombs reaction shows an incompatible minor cross-match, an indirect Coombs test should be performed. If this is negative, transfusion with blood compatible in the major cross-match may be carried out. If positive, the advisability of transfusion should be determined by a haematologist.
Reversible leucopenia, with primary effect on granulocytes has been reported rarely. The granulocyte count returned to normal on discontinuing therapy. Reversible thrombocytopenia has occurred rarely.
Occasionally, fever has occurred within the first three weeks of therapy, sometimes associated with eosinophilia or abnormalities in liver-function tests. Jaundice, with or without fever, also may occur. Its onset is usually within the first two or three months of therapy. In some patients the findings are consistent with those of cholestasis. Rare cases of fatal hepatic necrosis have been reported. Liver biopsy, performed in several patients with liver dysfunction, showed a microscopic focal necrosis compatible with drug hypersensitivity. Liver-function tests and a total and differential white blood-cell count are advisable before therapy and at intervals during the first six weeks to twelve weeks of therapy, or whenever an unexplained fever occurs.
Should fever, abnormality in liver function, or jaundice occur, therapy should be withdrawn. If related to methyldopa, the temperature and abnormalities in liver function will then return to normal. Methyldopa should not be used again in these patients. Methyldopa should be used with caution in patients with a history of previous liver disease or dysfunction.
Patients may require reduced doses of anaesthetics when on methyldopa. If hypotension does occur during anaesthesia, it can usually be controlled by vasopressors. The adrenergic receptors remain sensitive during treatment with methyldopa.
Dialysis removes methyldopa; therefore, hypertension may recur after this procedure.
Rarely, involuntary choreoathetotic movements have been observed during therapy with methyldopa in patients with severe bilateral cerebrovascular disease. Should these movements occur, therapy should be discontinued.
'Aldomet' should be used with extreme caution in patients, or in near relatives of patients, with hepatic porphyria.
Interference with laboratory tests:
Methyldopa may interfere with the measurement of urinary uric acid by the phosphotungstate method, serum creatinine by the alkaline picrate method, and AST (SGOT) by colorimetric method. Interference with spectrophotometric methods for AST (SGOT) analysis has not been reported.
As methyldopa fluoresces at the same wavelengths as catecholamines, spuriously high amounts of urinary catecholamines may be reported interfering with a diagnosis of phaeochromocytoma.
It is important to recognise this phenomenon before a patient with a possible phaeochromocytoma is subjected to surgery. Methyldopa does not interfere with measurements of VMA (vanillylmandelic acid) by those methods which convert VMA to vanillin.
Rarely, when urine is exposed to air after voiding, it may darken because of breakdown of methyldopa or its metabolites.
|Adverse Drug Reaction(s)||Peripheral oedema; drug fever, mental depression, anxiety, nightmares, drowsiness, headache; dry mouth; orthostatic hypotension, sinus bradycardia, sodium retention, sexual dysfunction, gynaecomastia, hyperprolactinaemia, thrombocytopenia, positive Coombs' test, transient leukopenia or granulocytopenia, cholestasis or hepatitis and heptocellular injury, increased liver enzymes, jaundice, cirrhosis, dyspnoea, SLE-like syndrome.
Potentially Fatal: Hepatic necrosis, haemolytic anaemia.
|Drug Interactions||Reduced hypotensive effects with phenothiazines, TCAs and possibly, amphetamines. Additive hypotensive effects with levodopa; psychosis may also occur. Reduced absorption and effects with oral iron preparations. Reduced doses of general anaesthetics may be required. Effect of ephedrinemay be reduced.
Potentially Fatal: Increased risk of severe hypertension with MAOIs. Increasedlithium toxicity.
|Food Interaction||Hypertension may be exacerbated with ephedra, yohimbe and ginseng. CNS depression may be increased when used with valerian, St John's wort, kava kava and gotu kola. Natural licorice causes sodium and water retention and increases potassium loss. Garlic may increase antihypertensive effect.|
|Lab Interference||Positive Coombs' test. May interfere with serum creatinine measurement by the alkaline picrate method and with AST estimation by colourimetric methods. May result in falsely high value for urinary catecholamines.|
|Pregnancy Category (FDA)||Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).|
It appears that several mechanisms of action for the clinically useful effects of methyldopa and the current generally accepted view is that its principal action is on the central nervous system.
The antihypertensive effect of methyldopa is probably due to its metabolism to alpha-methylnoradrenaline, which lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline).
Absorption of oral methyldopa is variable and incomplete. Bioavailability after oral administration averages 25%. Peak concentrations in plasma occur at two to three hours, and elimination of the drug is biphasic regardless of the route of administration. Plasma half-life is 1.8 Â± 0.2 hours. Renal excretion accounts for about two thirds of drug clearance from plasma.
|ATC Classification||C02AB - Methyldopa; Used in the treatment of hypertension.|
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|| See Brand Manufacturer's Prescribing Information |||| Methyldopa ||