- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Use in adults:Initial dosage: Usually 250 mg 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 daily dosage is 3 g.Many patients experience sedation for two or three days when therapy with 'Aldomet' is started or when the dose is increased. When increasing the dosage, therefore, it may be desirable to increase the evening dose first.Withdrawal of 'Aldomet' is followed by return of hypertension, usually within 48 hours. This is not complicated generally by an overshoot of blood pressure.Patients with renal impairment:Methyldopa is largely excreted by the kidney, and patients with impaired renal function may respond to smaller doses.
Other antihypertensives:Therapy with 'Aldomet' 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, '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 methyldopa is given to patients on other antihypertensives the dose of these agents may need to be adjusted to effect a smooth transition.When 500 mg of 'Aldomet' is added to 50 mg of hydrochlorothiazide, the two agents may be given together once daily.Paediatric population: initial dosage is based on 10 mg/kg of bodyweight daily in 2-4 oral doses. The daily dosage is then increased or decreased until an adequate response is achieved. The maximum dosage is 65 mg/kg or 3.0 g daily, whichever is less.Older people: The initial dose in elderly patients should be kept as low as possible, not exceeding 250 mg daily; an appropriate starting dose in the elderly would be 125 mg b.d. increasing slowly as required, but not to exceed a maximum daily dosage of 2 g. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses.
Method of administrationOral.
Lithium:When methyldopa and lithium are given concomitantly the patient should be monitored carefully for symptoms of lithium toxicity.
Other antihypertensive drugs:When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive action may occur. The progress of patients should be carefully followed to detect side reactions or manifestations of drug idiosyncrasy.
Other classes of drug: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.
Iron: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.
Pregnancy'Aldomet' has been used under close medical supervision for the treatment of hypertension during pregnancy. There was no clinical evidence that 'Aldomet' caused foetal abnormalities or affected the neonate.Published reports of the use of methyldopa during all trimesters indicate that if this drug is used during pregnancy the possibility of foetal harm appears remote.Methyldopa crosses the placental barrier and appears in cord blood.Although no obvious teratogenic effects have been reported, the possibility of foetal injury cannot be excluded and the use of the drug in women who are, or may become pregnant requires that anticipated benefits be weighed against possible risks.
Breast-feedingMethyldopa appears in breast milk. The use of the drug in breast-feeding mothers requires that anticipated benefits be weighed against possible risks.
|System Organ Class||Adverse event term||Frequency|
|Infections and infestations|| |
|Blood and lymphatic system disorders|| |
Haemolytic anaemia, bone-marrow failure, leukopenia, granulocytopenia, thrombocytopenia, eosinophilia
|Endocrine disorders|| |
|Psychiatric disorders|| |
Psychic disturbances including nightmares, reversible mild psychoses or depression, decreased libido
|Nervous system disorders|| |
Sedation (usually transient), headache, paraesthesia, Parkinsonism, VIIth nerve paralysis, choreoathetosis, mental impairment, carotid sinus syndrome, dizziness, symptoms of cerebrovascular insufficiency (may be due to lowering of blood pressure)
|Cardiac disorders|| |
Bradycardia, angina pectoris, myocarditis, pericarditis, atrioventricular block
|Vascular disorders|| |
Orthostatic hypotension (decrease daily dosage)
|Respiratory, thoracic and mediastinal disorders|| |
|Gastrointestinal disorders|| |
Nausea, vomiting, abdominal distension, constipation, flatulence, diarrhoea, colitis, dry mouth, glossodynia, tongue discolouration, pancreatitis
|Hepatobiliary disorders|| |
Liver disorders including hepatitis, jaundice
|Skin and subcutaneous tissue disorders|| |
Rash (eczema, lichenoid eruption), toxic epidermal necrolysis, angioedema, urticaria
|Musculoskeletal and connective tissue disorders|| |
Lupus-like syndrome, mild arthralgia with or without joint swelling, myalgia
|Reproductive system and breast disorders|| |
Breast enlargement, gynaecomastia, amenorrhoea, lactation disorder, erectile dysfunction, ejaculation failure
|General disorder and administration site conditions|| |
Asthenia, oedema (and weigh gain) usually relieved by use of a diuretic. (Discontinue methyldopa if oedema progresses or signs of heart failure appear). Pyrexia
Positive Coombs test, positive tests for antinuclear antibody, LE cells, and rheumatoid factor, abnormal liver-function tests, increased blood urea
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via; the Yellow Card Scheme at www.mhra.gov.uk/yellowcard
SymptomsAcute overdosage may produce acute hypotension with other responses attributable to brain and gastro-intestinal malfunction (excessive sedation, weakness, bradycardia, dizziness, light-headedness, constipation, distension, flatus, diarrhoea, nausea, and vomiting).
ManagementIf ingestion is recent, emesis may be induced or gastric lavage performed. There is no specific antidote. Methyldopa is dialysable. Treatment is symptomatic. Infusions may be helpful to promote urinary excretion. Special attention should be directed towards cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function and cerebral activity. Administration of sympathomimetic agents may be indicated. When chronic overdosage is suspected, 'Aldomet' should be discontinued.
Mechanism of actionIt appears that several mechanisms of action account 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).
AbsorptionAbsorption of oral methyldopa is variable and incomplete.
DistributionBioavailability after oral administration averages 25%.
BiotransformationPeak 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 ± 0.2 hours.
EliminationRenal excretion accounts for about two thirds of drug clearance from plasma.
Citric anhydrous acid
Collodial silicon dioxide
Edetate calcium disodium
Citric acid monohydrate
Quinoline yellow aluminium lake (E104)
Red iron oxide (E172)
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