Methyldopa oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulation of methyldopa
Drugs List
Therapeutic Indications
Uses
Hypertension
Dosage
Adults
The initial dose is 250 mg two or three times daily, for two days.
Increased at intervals of 2 days until an adequate response is achieved.
The maximum recommended daily dose should not exceed 3 g daily.
Elderly
The initial dose should be kept as low as possible, not exceeding 250 mg daily.
The recommended initial dose is 125 mg twice daily increasing gradually as required, maximum daily dose of 2 g.
Children
Children over 12 years
(See Dosage; Adult).
Children 1 to 12 years
The recommended initial dose is 10 mg/kg body weight daily in 2 to 4 divided doses, adjusted according to response. The maximum daily dose is 65 mg/kg or 3 g daily, whichever is less.
Patients with Renal Impairment
Methyldopa is excreted by the kidney and renally impaired patients may respond to smaller doses.
Additional Dosage Information
Patients wishing to switch from previous antihypertensive therapy should withdraw dose of old drug gradually.
When methyldopa is given to patients on other antihypertensives the dose of these agents may need to be adjusted to effect a smooth transition.
Withdrawal of methyldopa is usually followed by the return of hypertension, normally within 48 hours.
Patients may experience sedation during the first 2 or 3 days of therapy. When increasing dosage, it may be desirable to increase the evening dose first.
Contraindications
Children under 1 year
Catecholamine-secreting tumour
Depression
Hepatic cirrhosis
Hepatic disorder
Hepatitis
Porphyria
Precautions and Warnings
Anaesthesia
Family history of porphyria
Breastfeeding
Cerebrovascular disorder
History of depression
History of hepatic disorder
Pregnancy
Renal dialysis
Renal impairment
Advise patient drowsiness may affect ability to drive or operate machinery
Monitor differential WBC count before and during therapy
Perform liver function tests before commencing therapy and during therapy
May affect results of some laboratory tests
Disc. if muscle spasm occurs in bilateral cerebrovascular disease patients
Discontinue if fever occurs
Discontinue if haemolytic anaemia occurs
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if liver function tests become abnormal
Discontinue if oedema progresses or signs of cardiac failure occur
Advise patient not to take NSAIDs unless advised by clinician
Advise patient to moderate alcohol intake during treatment
If symptoms suggesting anaemia present, haemoglobin and/or haematocrit levels should be measured.
A positive Coombs test may occur within 6 to 12 months of therapy. Development of a positive result is dose dependent. The test usually becomes negative after weeks or months of stopping methyldopa therapy.
Prior knowledge of a positive Coombs reaction will aid in evaluating a cross-match for transfusion. If a patient with a positive Coombs test shows incompatibility with a minor cross-match, perform an indirect Coombs test. If negative, transfusion with blood compatible in the major cross-match may be carried out. If positive, a haematologist should determine the advisability of the transfusion.
Reversible leucopenia with primary effect on granulocytes has been reported rarely, but the granulocyte count has reverted back to normal on discontinuing therapy. Reversible thrombocytopenia has also been reported.
Fever has occasionally occurred during the first 3 weeks of treatment, sometimes associated with eosinophilia or abnormal liver function tests.
Jaundice with or without fever may also present during the first 2 or 3 months of treatment. Cholestasis and rarely fatal hepatic necrosis have occurred. As these effects are probably due to drug hypersensitivity, liver function tests, total and differential white blood cell counts are advisable before and at intervals during the first 6 to 12 weeks (or whenever an unexplained fever occurs). Methyldopa should not be used in these patients again.
Pregnancy and Lactation
Pregnancy
Use methyldopa with caution in pregnancy.
Schaefer (2007) states that when indicated, methyldopa is recommended for use as one of the first-line agents for the control of hypertension in pregnancy. Methyldopa crosses the placenta producing foetal concentrations similar to those in the mother (Briggs, 2011). Extensive use and published reports of exposure throughout pregnancy indicate that the possibility of foetal harm is remote. A small but significant decrease in head circumference has been observed in a small population exposed to methyldopa between 16 and 20 weeks gestation. Follow up at 6 and 12 months showed that the difference in head circumference had resolved and follow up at 4.5 and 7.5 years demonstrated no effect on growth or intelligence (Schaefer, 2007). Isolated cases of maternal hepatotoxicity following methyldopa treatment have occurred. Transient tremor, irritability and mildly decreased systolic blood pressure (lower by 4 to 5 mmHg in the first 48 hours of life) have been reported in neonates whose mothers have received chronic or near term methyldopa (Schaefer, 2007).
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Use methyldopa with caution in breastfeeding.
Methyldopa is excreted in small amounts into human breast milk, however, the amounts ingested by the infant are considered too small to cause any adverse effects.
Methyldopa can increase the serum prolactin level, with reported cases of maternal galactorrhoea. One case of gynaecomastia and galactorrhoea in a full term 2 week old female neonate following 7 days of maternal therapy has been reported (Hale, 2014). The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal distension
Abnormal liver function tests
Aggravation of angina
Amenorrhoea
Arthralgia
Asthenia
Atrioventricular block
Bell's palsy
Black tongue
Blood urea increased
Bone marrow depression
Bradycardia
Breast enlargement
Carotid sinus syndrome
Choreo-athetoid movements
Colitis
Constipation
Depression
Diarrhoea
Dizziness
Drowsiness
Drug fever
Dry mouth
Eczema
Eosinophilia
Failure of ejaculation
Flatus with discharge
Glossodynia
Granulocytopenia
Gynaecomastia
Haemolytic anaemia
Headache
Hepatitis
Hyperprolactinaemia
Impairment of mental skills
Impotence
Jaundice
Lactation
Leucopenia (reversible)
Lichenoid rash
Light-headedness
Lupus erythematosus-like syndrome
Myalgia
Myocarditis
Nasal congestion
Nausea
Nightmares
Oedema
Orthostatic hypotension
Pancreatitis
Paraesthesia
Parkinsonism
Pericarditis
Positive ANA titre
Positive Coombs test
Possible alteration of laboratory tests
Psychiatric disorders
Psychotic episodes (transient)
Rash
Reduced libido
Sedation
Sialadenitis
Stomatitis
Thrombocytopenia
Toxic epidermal necrolysis
Vomiting
Weakness
Weight gain
Effects on Laboratory Tests
Methyldopa may interfere with measurements of:
Urinary uric acid taken via the phosphotungstate method;
Serum creatinine by the alkaline picrate method;
AST (SGOT) by colorimetric method.
May interfere with the diagnosis of phaeochromocytoma as methyldopa fluoresces at the same wavelength as catecholamines.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: February 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on 17 February 2016.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Aldomet tablets 250mg. Aspen. Revised November 2015.
Summary of Product Characteristics: Aldomet tablets 500mg. Aspen. Revised November 2015.
Summary of Product Characteristics: Methyldopa tablets BP 125mg. Actavis UK Ltd. Revised April 2007.
Summary of Product Characteristics: Methyldopa tablets BP 250mg. Actavis UK Ltd. Revised April 2007.
Summary of Product Characteristics: Methyldopa tablets BP 500mg. Actavis UK Ltd. Revised April 2007.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Methyldopa Last revised: 10 March, 2015
Last accessed: 17 February, 2016.
The Drug database for acute porphyria (NAPOS).
Available at: https://www.drugs-porphyria.org/languages/UnitedKingdom/s3.php?atc_code=C02AB01&l=gbr
Methyldopa Last revised: 15 May, 2007
Last accessed: 17 February, 2016.
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