Hypertension (mild, moderate, or severe)

Adults

The usual starting dose of Aldomet® is 250 mg two or three times a day in the first 48 hours. The daily dosage may be increased or decreased preferably at intervals not less than two days, until an adequate response is achieved. The maximum recommended daily dose is 3g.

Many patients experience sedation for two or three days when therapy is started or when the dose is increased. When increasing the dosage, therefore, it may be desirable to increase the evening dose first.

 

General  considerations

Methyldopa is largely excreted by the kidney, and patients with impaired renal function may respond to smaller doses.

Withdrawal of ‘Aldomet’ is followed by return of hypertension, usually within 48 hours. This is not complicated generally by an overshoot of blood pressure.

Therapy with ‘Aldomet’ may be initiated in most patients already on treatment with other antihypertensive agents by terminating these antihypertensive medications gradually if required (see manufacturer’s recommendations on stopping these drugs). Following such previous antihypertensive therapy, ‘Aldomet ’ 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 500 mg of 'Aldomet' is added to 50 mg of hydrochlorothiazide, the two agents may be given together once daily. ‘Aldomet’ may also be used concomitantly with the combination of amiloride hydrochloride and hydrochlorothiazide or beta-blocking agents, such as timolol maleate.

When methyldopa is given to patients on other antihypertensives the dose of these agents may need to be adjusted to effect a smooth transition.

 

Children

Initial dosage is based on 10 mg/kg of body weight daily in two to four doses. The daily dosage is then increased or decreased until an adequate response is achieved. The maximum dosage is 65 mg/kg or 3 g daily, whichever is less.

 

Elderly

Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses. Initially no more than 250mg a day (i.e. 125mg twice daily), increasing slowly up to a maximum of 2g a day.

 

Aldomet® is contraindicated in patients: ∗ with active hepatic disease (such as acute hepatitis and active cirrhosis) ∗ with hypersensitivity to any of the components of this product (including hepatic disorders associated with previous methyldopa therapy) ∗ with phaeochromocytoma ∗ with depression ∗ on therapy with monoamine oxidase inhibitors (MAOIs)

Acquired haemolytic anemia has occurred rarely. Should symptoms suggest anemia, hemoglobin and/or hematocrit determinations should be made. If anemia is confirmed, tests should be done for hemolysis. If haemolytic anemia is present, the drug should be discontinued. Stopping therapy, with or without giving a corticosteroid, has usually brought prompt remission. Rarely, however, fatalities have occurred.

 

Some patients on continued therapy with methyldopa develop a positive direct Coombs test. From the reports of different investigators, the incidence averages between 10 to 20% of patients. A positive Coombs test rarely develops in the first six months of therapy with methyldopa, and if not encountered within 12 months, is unlikely to develop with continued administration. This phenomenon is also dose-related with the lowest incidence occurring in patients receiving ≤ 1 g of methyldopa per day. Reversal of the positive Coombs test occurs within weeks to months after discontinuation of the drug.

 

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 hematologist.

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.

Caution is required in patients with renal impairment (start with small dose as there may be increased sensitivity to hypotensive and sedative effect).

 

Methyldopa should be given with caution in patients with history of depression (see section 4.3– Contraindications).

 

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 count are advisable 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 anesthetics when on methyldopa. If hypotension does occur during anesthesia, 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.

 

Methyldopa 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 calorimetric 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 and paraganglioma. It is important to recognize 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 the breakdown of methyldopa or its metabolites.

Taking Aldomet® with other medicines  

 

	∗	Alcohol: concomitant use may enhance the hypotensive effect.
	∗	Alprostadil: concomitant use may enhance the hypotensive effect.
	∗	Anaesthetics: as concomitant use may enhance the hypotensive effect, patients may require reduced doses of anaesthetics when on methyldopa. If hypotension does occur during anaesthesia, it can usually be controlled by vasopressors.
	∗	Analgesics: NSAIDs antagonise the hypotensive effect.
	∗	Antibacterials: concomitant use with linezolid should be avoided as the hypotensive effect may be enhanced.
	∗	Antidepressants: concomitant use may enhance the hypotensive effect. Concomitant use with MAOIs should be avoided.
	∗	Antihypertensives: the use of other antihypertensives may enhance the hypotensive effect. The progress of patients should be carefully monitored to detect side-effects or manifestations of drug idiosyncrasy.
	∗	Antipsychotics: concomitant use can increase the risk of extrapyrimidal effects and enhance the hypotensive effect.
	∗	Anxiolytics and hypnotics: concomitant use may enhance the hypotensive effect.
	∗	Beta-blockers: concomitant use may enhance the hypotensive effect.
	∗	Calcium-channel blockers: concomitant use may enhance the hypotensive effect.
	∗	Corticosteroids: concomitant use may antagonise the hypotensive effect.
	∗	Diuretics: concomitant use may enhance the hypotensive effect.
	∗	Dopaminergics: concomitant use may antagonise the antiparkinsonian effect of this type of medicine. Concomitant use with levodopa or entacapone may enhance the hypotensive effect.
	∗	Iron: concomitant use may reduce the hypotensive effect. Several studies demonstrate a decrease in the bioavailability of methyldopa when it is ingested with ferrous sulphate or ferrous gluconate. This may adversely affect blood pressure control in patients treated with methyldopa.
∗		Lithium: when methyldopa and lithium are given concomitantly the patient should be monitored carefully for symptoms of lithium toxicity.
∗		Moxisylyte: concomitant use may enhance the hypotensive effect.
∗		Muscle relaxants: concomitant use with baclofen and tizanidine may enhance the hypotensive effect.
∗		Nitrates: concomitant use may enhance the hypotensive effect.
∗		Oestrogens and progestogens: oestrogens and combined oral contraceptives antagonise the hypotensive effect.
∗		Beta2 sympathomimetics: acute hypotension has been reported with salbutamol infusion.
∗		Ulcer-healing drugs: carbenoxolone antagonises the hypotensive effect.
∗		Other: The antihypertensive effect of 'Aldomet' may be diminished by sympathomimetics, phenothiazines, tricyclic antidepressants and MAOIs (see 4.3 'Contra-indications'). In addition, phenothiazines may have additive hypotensive effects

Taking Aldomet® with food and alcohol  

 Drinking alcohol with Aldomet® may make you feel dizzy or light-headed. If you are concerned about how much you can drink while you are taking Aldomet®, discuss this with your doctor as medicines used to reduce blood pressure and alcohol can have additive effects.  Aldomet® may be taken with or without food. 

 

Although there are no clinical evidence that methyldopa caused fetal abnormalities or affected the neonate and although no teratogenicity effects have been reported, fetal damage cannot be excluded and the use of methyldopa in women who are, or who may become, pregnant or who are nursing their new born infant demands that dosage benefits be weighed against the possible risks.

 

Methyldopa crosses the placental barrier and appears in the cord blood and in breast milk. The use of the drug in breast-feeding mothers requires that anticipated benefits be weighed against possible risks

Drowsiness may affect performance at skilled tasks such as driving or operating machines. Patients should avoid performing tasks which require special attention.

 

Sedation, usually transient, may occur during the initial period of therapy or whenever the dose is increased. Headache, asthenia or weakness may be noted as early and transient symptoms.

 

The following reactions have been reported:

 

∗ Central  Nervous  System:  Sedation  (usually  transient),  headache,  asthenia  or  weakness), paraesthesiae, parkinsonism, Bell’s palsy, involuntary choreoathetotic movements. Psychic disturbances including nightmares, impaired mental acuity and reversible mild psychoses or depression. Dizziness, lightheadedness, and symptoms of cerebrovascular insufficiency (may be due to lowering of blood pressure). ∗ Cardiovascular: Bradycardia, prolonged carotid sinus hypersensitivity, aggravation of angina pectoris. Atrioventricular block. Orthostatic hypotension (decrease daily dosage). Edema (and weight gain) usually relieved by use of a diuretic. (Discontinue methyldopa if edema progresses or signs of heart failure appear).

∗ Gastro-intestinal: Nausea, vomiting, distension, constipation, flatus, diarrhea, colitis, mild dryness of mouth, sore or ‘black’ tongue, stomatitis, pancreatitis, sialadenitis

        ∗          Hepatic: Liver disorders including hepatitis, jaundice, and abnormal liver function tests.

∗ Hematological: Positive Coombs test, haemolytic anemia, bone marrow depression, leucopenia, granulocytopenia, thrombocytopenia and eosinophilia. Positive tests for anti-nuclear antibody. LE cells, and rheumatoid factor.

∗ Allergic: Drug-related fever and abnormal liver function tests with jaundice and hepatocellular damage, lupus erythematosus-like syndrome, myocarditis and pericarditis.

        ∗          Dermatological: Rash as in eczema or lichenoid eruption, toxic epidermal necrolysis.

        ∗     Endocrine: hyperprolactinemia

        ∗      Respiratory, thoracic and mediastinal disorders: Nasal congestion     

∗ Psychiatric disorders: Psychic disturbances including nightmares, reversible mild psychoses or depression, decreased libido 

∗ Other: rise in blood urea, breast enlargement, gynaecomastia, amenorrhoea,  lactation,  failure  of  ejaculation,  impotence, mild arthralgia with or without joint swelling, myalgia.

 

To report any side effect(s): · Saudi Arabia: National Pharmacovigilance and Drug Safety Center (NPC)

Call NPC at +966-11-2038222,

Exts: 2317-2356-2340

•  Fax: +966-11-205-7662

•  Toll-free: 8002490000

•  Email: npc.drug@sfda.gov.sa

•  Website: www. sfda.gov.sa/npc

Overdose may produce acute hypotension manifested through excessive sedation, weakness, dizziness, light-headedness, bradycardia, distension, constipation, nausea and vomiting.

In the event of overdosage, symptomatic and supportive measures should be employed. When ingestion is recent, gastric lavage or emesis may reduce absorption. When ingestion has been earlier, infusions may be helpful to promote urinary excretion.

Careful attention should be paid to cardiac rate and output, electrolyte balance, blood volume., urinary function, cerebral activity and paralytic ileus.

The patient should preferably be observed in a recumbent position, possibly in combination with intravenous saline administration. Administration of norepinephrine (noradrenalin) may be indicated. Methyldopa is dialyzable

 

Methyldopa acts by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. It is suggested that a metabolite, alpha-methylnoradrenaline, may act as a false transmitter in the central nervous system. Methyldopa reduces the tissue concentrations of dopamine, noradrenaline, adrenaline, and serotonin.

 

When administered by mouth its effects may appear after about two hours and reach a maximum in 6 to 8 hours, although the maximum hypotensive effect may not occur until the second day of treatment; some effect is still usually apparent until 48 hours after a dose.

Absorption

The   absorption   of methyldopa   shows   wide   individual   variations.   In   two   studies   the bioavailability of methyldopa was in the range of 8 to 62%. 

 

Metabolism

Methyldopa is extensively metabolized. The known urinary metabolites are: alpha-methyldopa mono-0sulfate; 3-0-methyl-alpha-methyldopa; 3.4-dihydroxy-phenylacetone; alpha- methyldopamine; 3-0-methylalpha-methyl-dopamine and their conjugates.

 

Excretion

Approximately 70% of the oral form of the drug which is absorbed is excreted in the urine as methyldopa and its mono-0-sulfate conjugate. The renal clearance is about 130mL/min in normal subjects and is diminished in renal insufficiency. Renal impairments may increase the half-life to about 3.6 hours; elimination is then 50%. The plasma half-life of methyldopa is about 2 hours. After oral doses, excretion is essentially complete in 36 hours.

 

Methyldopa crosses the placental barrier, appears in cord blood, and appears in breast milk.

 

No particulars

Citric Acid (E 330), ethylcellulose, colloidal silicon dioxide (E 551), guar gum, sodium calcium edetate, cellulose, magnesium stearate (E 572), iron oxide red (E 172), talc (E553b), quinolone yellow aluminum lake (E 104), titanium dioxide (E 171), hydroxypropylmethylcellulose (E 464), propylene glycol.

 

No particulars. 

Two years. The expiry date is printed on the package after “not to be used after” and on the blister after “exp”, followed by month and year.

Do not store above 30C, store in the original package

Box with ten PVC/Al blister strips with ten tablets each of 250 mg or 500 mg.  EAV: ten PVC/Al blister strips with 5 tablets of 250 mg

 

No particulars.